The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy of Oral Azacitidine Plus Best Supportive Care as Maintenance Therapy in Subjects With Acute Myeloid Leukemia (AML) in Complete Remission (QUAZAR AML-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01757535
Recruitment Status : Active, not recruiting
First Posted : December 31, 2012
Results First Posted : November 6, 2020
Last Update Posted : January 19, 2024
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Leukemia, Myeloid, Acute
Interventions Drug: Oral Azacitidine
Drug: Placebo
Enrollment 472
Recruitment Details Participants were randomized at 147 investigational sites within Europe: Italy, Germany, Spain, United Kingdom, France, Turkey, Austria, Poland, Portugal, Russian Federation, Belgium, Israel, Czech Republic, Ireland, Lithuania, Finland, the United States, Canada, Mexico, Australia, South Korea, Taiwan, and Brazil.
Pre-assignment Details

Participants were randomized to oral azacitidine or placebo and stratified by:

  • Age (at induction therapy)- 55-64 years versus (VS) ≥ 65 years
  • Prior history of myelodysplatic syndromes or chronic myelomonocytic leukemia
  • Cytogenetic risk (induction therapy): intermediate-risk VS poor-risk
  • Given consolidation therapy after induction- Yes/No
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.
Period Title: Overall Study
Started [1] 238 234
Received Treatment 236 233
Completed [2] 45 26
Not Completed 193 208
Reason Not Completed
Disease Relapse             143             180
Adverse Event             29             11
Withdrawal by Subject             9             13
Miscellaneous             5             2
Physician Decision             6             0
Death             1             2
[1]
Treatment Phase
[2]
Completed = treatment ongoing
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care Total
Hide Arm/Group Description Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study. Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. Total of all reporting groups
Overall Number of Baseline Participants 238 234 472
Hide Baseline Analysis Population Description
The intent to treat (ITT) population includes participants who were randomized, regardless of whether they received treatment or not.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 238 participants 234 participants 472 participants
67.9  (5.72) 68.0  (5.62) 67.9  (5.66)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 238 participants 234 participants 472 participants
18 to 64 Years
66
  27.7%
68
  29.1%
134
  28.4%
65 to 84 Years
171
  71.8%
166
  70.9%
337
  71.4%
≥ 85 years
1
   0.4%
0
   0.0%
1
   0.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 238 participants 234 participants 472 participants
Female
120
  50.4%
107
  45.7%
227
  48.1%
Male
118
  49.6%
127
  54.3%
245
  51.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 238 participants 234 participants 472 participants
Hispanic or Latino
20
   8.4%
14
   6.0%
34
   7.2%
Not Hispanic or Latino
196
  82.4%
202
  86.3%
398
  84.3%
Unknown or Not Reported
22
   9.2%
18
   7.7%
40
   8.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 238 participants 234 participants 472 participants
White
216
  90.8%
197
  84.2%
413
  87.5%
Black or African-American
2
   0.8%
6
   2.6%
8
   1.7%
Asian
6
   2.5%
20
   8.5%
26
   5.5%
Other
12
   5.0%
11
   4.7%
23
   4.9%
Missing
2
   0.8%
0
   0.0%
2
   0.4%
Initial Acute Myeloid Leukemia (AML) Classification   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 238 participants 234 participants 472 participants
AML with Recurrent Genetic Abnormalities
39
  16.4%
46
  19.7%
85
  18.0%
AML with Myelodysplasia - Related Changes
49
  20.6%
42
  17.9%
91
  19.3%
Therapy-related Myeloid Neoplasms
2
   0.8%
0
   0.0%
2
   0.4%
AML not Otherwise Specified
148
  62.2%
145
  62.0%
293
  62.1%
Missing
0
   0.0%
1
   0.4%
1
   0.2%
[1]
Measure Description:

AML is classified using the WHO classification system based upon a combination of morphology, immunophenotype, genetics, and clinical features. There are several broad groups and include:

  1. AML with genetic abnormalities;
  2. AML with multilineage dysplasia
  3. AML related to previous chemotherapy or radiation
  4. Unspecified AML - do not fall into the above groups
Type of Acute Myeloid Leukemia (AML)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 238 participants 234 participants 472 participants
Primary (de novo)
213
  89.5%
216
  92.3%
429
  90.9%
Secondary
25
  10.5%
18
   7.7%
43
   9.1%
[1]
Measure Description: Primary AML is a cancer that originates in the blood and bone marrow. AML affects a group of white blood cells called myeloid cells, which normally develop into the various types of mature blood cells, such as red blood cells, white blood cells and platelets. Secondary acute myeloid leukemia (s-AML) refers to a leukemic process: (1) evolving from prior myelodysplasia (MDS), myeloproliferative disorder (MPN), or aplastic anemia (AA) with or without treatment or (2) as a product of previous exposure to a proven leukemogenic chemotherapeutic agent (therapy-related AML [t-AML]).
Cytogenetic Risk Category at Diagnosis   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 238 participants 234 participants 472 participants
Intermediate
203
  85.3%
203
  86.8%
406
  86.0%
Poor
35
  14.7%
31
  13.2%
66
  14.0%
[1]
Measure Description: Cytogenetic Risk - Intermediate -I is of a normal karyotype; Poor Risk - includes complex karyotypes having 3 or more cytogenetic abnormalities.
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 238 participants 234 participants 472 participants
Grade 0
116
  48.7%
111
  47.4%
227
  48.1%
Grade 1
101
  42.4%
106
  45.3%
207
  43.9%
Grade 2
21
   8.8%
15
   6.4%
36
   7.6%
Grade 3
0
   0.0%
2
   0.9%
2
   0.4%
[1]
Measure Description: ECOG performance status is used to describe a patient's level of functioning in terms of their ability to care for themselves, daily activity, and physical ability (walking, working, etc.). The scale ranges from 0 to 5: 0 = Fully active, no restrictions; 1 = Restricted activity but ambulatory, able to carry out work of a light nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities; 3 = Capable to only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled, no self-care, confined to bed or chair; 5 = Dead.
1.Primary Outcome
Title Kaplan-Meier (K-M) Estimate for Overall Survival (OS)
Hide Description Overall survival was defined as time from randomization to death from any cause; participants surviving at the end of the follow-up period, or who withdraw consent, or who were lost to follow up were censored at the date last known alive.
Time Frame Day 1 (randomization) up to data cut off date of 15 July 2019; median follow-up for OS estimated by the reverse K-M method was 41.2 months for all participants.
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat (ITT) population includes participants who were randomized, regardless of whether they received treatment or not.
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.
Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.
Overall Number of Participants Analyzed 238 234
Median (95% Confidence Interval)
Unit of Measure: Months
24.7
(18.7 to 30.5)
14.8
(11.7 to 17.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments The p-value is 2-sided from a log-rank test stratified by age, cytogenetic risk category, and received consolidation therapy or not.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.55 to 0.86
Estimation Comments The hazard ratio is from a Cox proportional hazards model stratified by age, cytogenetic risk category, and received consolidation therapy or not.
Other Statistical Analysis The confidence interval (CI) for the difference was derived using Kosorok's method.
2.Secondary Outcome
Title Kaplan-Meier Estimate of Relapse Free Survival (RFS)
Hide Description

RFS was defined as the time from the date of randomization to the date of documented relapse or death from any cause, whichever occurred first. Participants who were still alive without documented relapse, or who were lost to follow-up or withdrew consent without documented relapse, were censored at the date of their last bone marrow assessment, prior to receiving any other therapy for AML.

Documented relapse was defined as the earliest date of the following:

  • ≥ 5% bone marrow blasts (myeloblasts) from Central Pathology report, or
  • appearance of > 0% blasts in the peripheral blood with a later bone marrow confirmation (bone marrow blast [myeloblasts] ≥ 5%) within 100 days, or
  • at least 2 peripheral blasts ≥ 5% within 30 days.
Time Frame From day 1 (randomization) up to data cut off date of 15 July 2019; approximately 74 months
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population includes participants who were randomized, regardless of whether they received treatment or not.
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.
Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.
Overall Number of Participants Analyzed 238 234
Median (95% Confidence Interval)
Unit of Measure: Months
10.2
(7.9 to 12.9)
4.8
(4.6 to 6.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments The p-value is 2-sided from a log-rank test stratified by age, cytogenetic risk category, and received consolidation therapy or not.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.52 to 0.81
Estimation Comments The hazard ratio is from a Cox proportional hazards model stratified by age, cytogenetic risk category, and received consolidation therapy or not.
3.Secondary Outcome
Title Kaplan-Meier Estimate of Time to Relapse
Hide Description

Time to relapse was defined as the interval (in months) from the date of randomization to the date of documented relapse. Estimates of relapse rate were based on the cumulative incidence function from a competing risk analysis with death as a competing risk for relapse from complete remission (CR)/ complete remission with incomplete blood count recovery (CRi).

Documented relapse was defined as, the earliest date of the following:

  • ≥ 5% bone marrow blasts (myeloblasts) from Central Pathology report, or
  • appearance of > 0% blasts in the peripheral blood with a later bone marrow confirmation (bone marrow blast [myeloblasts] ≥ 5%) within 100 days, or
  • at least 2 peripheral blasts ≥ 5% within 30 days.
Time Frame Day 1 (randomization) to the date of the data cut off date of 15 July 2019; approximately 74 months
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population includes participants who were randomized, regardless of whether they received treatment or not.
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.
Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.
Overall Number of Participants Analyzed 238 234
Median (95% Confidence Interval)
Unit of Measure: months
10.2
(8.3 to 13.4)
4.9
(4.6 to 6.4)
4.Secondary Outcome
Title Kaplan-Meier Estimates of Time to Discontinuation From Treatment
Hide Description Time to discontinuation from treatment was assessed and defined as the interval from the date of randomization to the date of discontinuation from study drug. Participants who were receiving treatment at the time of study closure were censored at the date of last visit. Estimates of relapse rate were based on the cumulative incidence function from a competing risk analysis with death as a competing risk for relapse from CR/ CRi.
Time Frame From day 1 (randomization) up to data cut off date of 15 July 2019; approximately 74 months
Hide Outcome Measure Data
Hide Analysis Population Description
The intent to treat population includes participants who were randomized, regardless of whether they received treatment or not.
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.
Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.
Overall Number of Participants Analyzed 238 234
Median (95% Confidence Interval)
Unit of Measure: months
11.4
(9.8 to 13.6)
6.1
(5.1 to 7.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 5.4
Confidence Interval (2-Sided) 95%
3.1 to 7.8
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Hide Description

TEAEs include AEs that started between first dose date and 28 days after the last dose of study drug.

A serious adverse event (SAE) is:

  • Death
  • Life-threatening event
  • Inpatient hospitalization or prolongation of existing hospitalization
  • Persistent or significant disability or incapacity
  • Congenital anomaly or birth defect
  • Other important medical event The severity of AEs were assessed by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0: Grade 1 (Mild): asymptomatic/mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 (Moderate): minimal, local or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care Grade 4: Life-threatening; urgent intervention indicated. Grade 5: Death due to AE.
Time Frame Day 1 (randomization) to the data cut off date of 15 July 2019; the median treatment duration was 11.6 months (range: 0.5 to 74.3 months) for the oral aza arm and 5.7 months (range: 0.7 to 68.5 months) for the placebo arm.
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all randomized participants who received at least 1 dose of study drug.
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.
Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.
Overall Number of Participants Analyzed 236 233
Measure Type: Count of Participants
Unit of Measure: Participants
≥ 1 TEAE
231
  97.9%
225
  96.6%
≥ 1 TEAE Related to Study Treatment
212
  89.8%
120
  51.5%
≥ 1 Serious TEAE
79
  33.5%
60
  25.8%
≥ 1 Treatment Related Serious TEAE
22
   9.3%
5
   2.1%
≥ 1 Grade 3/4 TEAE
169
  71.6%
147
  63.1%
≥ 1 Treatment Related Grade 3/4 TEAE
113
  47.9%
54
  23.2%
≥ 1 TEAE Leading to Death
9
   3.8%
4
   1.7%
≥ 1 TEAE Leading to Dose Reduction (Red)
37
  15.7%
6
   2.6%
≥ 1 TEAE Leading to Dose Interruption
102
  43.2%
40
  17.2%
≥ 1 TEAE Leading to Dose Red and Interruption
24
  10.2%
3
   1.3%
≥ 1 TEAE Leading to Study Drug Discontinuation
31
  13.1%
10
   4.3%
6.Secondary Outcome
Title Mean Change in the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue Scale V 4.0) Score From Baseline
Hide Description The functional assessment of chronic illness therapy (FACIT-Fatigue Scale V 4.0) is a subscale of the FACIT-F and has been validated in the oncology setting. The FACIT-Fatigue Scale is a short, 13-item, self-administered tool that measures the level of fatigue in an individual during usually daily activities over the past week. The level of fatigue is measured on a 5-point Likert scale (0 = not at all; 4 = very much. The scores range from 0 to 52, with higher scores indicating less fatigue. If there were missing items, but the participant answered at least 50% of the items, then subscores were prorated.
Time Frame Baseline to Cycle 2, Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1C3, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, C23D1, C24D1, C25D1 and continued on day 1 at each cycle through C33D1
Hide Outcome Measure Data
Hide Analysis Population Description
The Health Related Quality of Life (HRQoL) evaluable population was defined as the ITT participants with a non-missing FACIT-Fatigue score at baseline (C1D1) and at least one post-baseline visit. Visits are presented for each post-baseline visit with sample size ≥ 25 in both arms.
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.
Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.
Overall Number of Participants Analyzed 225 219
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Change from Baseline (CFB) at Cycle 2 Day 1 Number Analyzed 200 participants 205 participants
0.6  (7.38) 0.3  (7.40)
CFB at C3 D1 Number Analyzed 190 participants 183 participants
0.5  (7.95) 1.6  (7.27)
CFB at C4 D1 Number Analyzed 185 participants 160 participants
0.8  (8.50) 1.3  (7.47)
CFB at C5 D1 Number Analyzed 176 participants 144 participants
0.9  (7.88) 1.6  (8.22)
CFB at C6 D1 Number Analyzed 167 participants 128 participants
0.7  (8.18) 1.1  (8.39)
CFB at C7 D1 Number Analyzed 152 participants 98 participants
0.4  (8.82) 1.8  (8.39)
CFB at C8 D1 Number Analyzed 146 participants 100 participants
0.4  (8.11) 1.5  (7.98)
CFB at C9 D1 Number Analyzed 139 participants 87 participants
0.3  (7.42) 0.5  (7.95)
CFB at C10 D1 Number Analyzed 130 participants 78 participants
1.0  (7.98) 1.6  (7.75)
CFB at C11 D1 Number Analyzed 125 participants 78 participants
1.0  (7.19) 1.5  (8.46)
CFB at C12 D1 Number Analyzed 121 participants 71 participants
0.9  (8.02) 1.6  (9.25)
CFB at C13 D1 Number Analyzed 109 participants 60 participants
1.3  (7.27) 2.9  (8.28)
CFB at C14 D1 Number Analyzed 102 participants 62 participants
1.1  (7.19) 1.1  (10.12)
CFB at C15 D1 Number Analyzed 96 participants 55 participants
1.6  (7.36) 2.6  (7.24)
CFB at C16 D1 Number Analyzed 92 participants 51 participants
1.9  (6.89) 1.5  (8.70)
CFB at C17 D1 Number Analyzed 86 participants 47 participants
1.9  (7.03) 2.4  (7.44)
CFB at C18 D1 Number Analyzed 87 participants 44 participants
1.1  (7.34) 2.0  (8.82)
CFB at C19 D1 Number Analyzed 79 participants 41 participants
1.7  (8.06) 1.8  (8.93)
CFB at C20 D1 Number Analyzed 76 participants 40 participants
1.3  (8.05) 3.6  (7.84)
CFB at C21 D1 Number Analyzed 75 participants 40 participants
1.1  (9.19) 2.5  (8.57)
CFB at C22 D1 Number Analyzed 68 participants 38 participants
0.6  (8.16) 3.2  (8.25)
CFB at C23 D1 Number Analyzed 72 participants 35 participants
1.0  (8.22) 3.2  (8.37)
CFB at C24 D1 Number Analyzed 70 participants 34 participants
0.6  (9.96) 2.6  (8.89)
CFB at C25 D1 Number Analyzed 68 participants 31 participants
0.5  (7.97) 1.3  (9.73)
CFB at C26 D1 Number Analyzed 65 participants 30 participants
0.8  (9.76) 2.5  (8.81)
CFB at C27 D1 Number Analyzed 62 participants 32 participants
0.9  (9.39) 2.6  (7.85)
CFB at C28 D1 Number Analyzed 61 participants 31 participants
1.0  (8.45) 1.6  (8.69)
CFB at C29 D1 Number Analyzed 59 participants 31 participants
-0.3  (9.76) 2.7  (7.69)
CFB at C30 D1 Number Analyzed 53 participants 32 participants
1.3  (7.83) 3.1  (8.58)
CFB at C31 D1 Number Analyzed 48 participants 32 participants
0.5  (6.69) 2.9  (7.07)
CFB at C32 D1 Number Analyzed 49 participants 29 participants
0.3  (6.15) 2.8  (7.17)
CFB at C33 D1 Number Analyzed 46 participants 24 participants
-0.2  (7.10) 2.8  (5.99)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments Cycle 2 Day 1 (C2, D1)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.711
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C3, D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.132
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C4, D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.604
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C5, D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.393
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C6 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.733
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments C7 D1
Statistical Test of Hypothesis P-Value 0.217
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C8 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.308
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C9 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.868
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C10 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.622
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments C11 D1
Statistical Test of Hypothesis P-Value 0.603
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments C12 D1
Statistical Test of Hypothesis P-Value 0.553
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C13 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.196
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C14 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.955
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C15 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.416
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C16 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.746
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C17 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.692
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C18 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.518
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C19 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.947
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C20 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.139
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C21 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.421
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C22 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.129
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C23 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.208
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C24 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.326
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C25 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.682
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C26 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.431
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C27 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.380
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C28 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.719
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C29 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.137
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C30 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.317
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C31 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.128
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C32 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.120
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C33 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.083
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
7.Secondary Outcome
Title Mean Change in the European Quality of Life-Five Dimensions-Three Levels (EQ-5D-3L) Score From Baseline
Hide Description The EQ-5D-3L is a self-administered questionnaire consisting of 5 questions, pertaining to specific health dimensions (ie, mobility, self-care, pain, usual activities, and anxiety/depression) and a health status scale. Each question has 3 levels of severity, corresponding to no problems, moderate problems and severe problems. Canadian population sample weights were used to derive health utility scores. A higher utility score represents a better health state. A clinically meaningful improvement or worsening was defined as at least 0.08 points of improvement or 0.10 points of worsening from baseline, respectively, for the EQ-5D-3L Health Utility Index. The instrument is scored using the United Kingdom (UK) index ranges from -0.594 to 1, where 0 equates to death and 1 equates to full health; -0.594 is considered 'worse than death'.
Time Frame Baseline to Cycle 2, Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1C3, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, C23D1, C24D1, C25D1 and continued on day 1 at each cycle through C33D1
Hide Outcome Measure Data
Hide Analysis Population Description
The Health Related Quality of Life (HRQoL) evaluable population was defined as the ITT participants with a non-missing EQ-5D-3L score at baseline (C1D1) and at least one post-baseline visit. Visits are presented for each post-baseline visit with sample size ≥ 25 in both arms.
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.
Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.
Overall Number of Participants Analyzed 225 217
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
Change from Baseline (CFB) at Cycle 2 Day 1 Number Analyzed 199 participants 202 participants
0.0017  (0.0859) 0.0107  (0.1049)
CFB at C3 D1 Number Analyzed 189 participants 183 participants
0.0042  (0.0929) 0.0122  (0.1222)
CFB at C4 D1 Number Analyzed 183 participants 158 participants
0.0085  (0.0861) 0.0230  (0.1024)
CFB at C5 D1 Number Analyzed 174 participants 142 participants
0.0049  (0.0902) 0.0164  (0.1107)
CFB at C6 D1 Number Analyzed 165 participants 126 participants
0.0096  (0.0807) 0.0148  (0.1290)
CFB at C7 D1 Number Analyzed 150 participants 96 participants
0.0115  (0.0937) 0.0217  (0.0886)
CFB at C8 D1 Number Analyzed 145 participants 99 participants
-0.0011  (0.1045) 0.0259  (0.1205)
CFB at C9 D1 Number Analyzed 138 participants 85 participants
-0.0055  (0.1054) 0.0245  (0.1291)
CFB at C10 D1 Number Analyzed 130 participants 76 participants
0.0112  (0.0939) 0.0103  (0.1485)
CFB at C11 D1 Number Analyzed 125 participants 75 participants
0.0198  (0.0853) 0.0364  (0.1149)
CFB at C12 D1 Number Analyzed 121 participants 68 participants
0.0080  (0.0900) 0.0276  (0.1189)
CFB at C13 D1 Number Analyzed 108 participants 59 participants
0.0210  (0.0833) 0.0386  (0.1234)
CFB at C14 D1 Number Analyzed 101 participants 61 participants
0.0127  (0.1050) 0.0135  (0.1620)
CFB at C15 D1 Number Analyzed 96 participants 54 participants
0.0199  (0.0900) 0.0307  (0.1254)
CFB at C16 D1 Number Analyzed 92 participants 51 participants
0.0161  (0.0883) 0.0415  (0.1309)
CFB at C17 D1 Number Analyzed 85 participants 46 participants
0.0109  (0.1057) 0.0494  (0.1369)
CFB at C18 D1 Number Analyzed 87 participants 44 participants
0.0162  (0.0923) 0.0359  (0.1468)
CFB at C19 D1 Number Analyzed 79 participants 41 participants
0.0125  (0.1002) 0.0436  (0.1359)
CFB at C20 D1 Number Analyzed 76 participants 40 participants
0.0088  (0.1008) 0.0505  (0.1410)
CFB at C21 D1 Number Analyzed 75 participants 40 participants
0.0087  (0.1203) 0.0566  (0.1388)
CFB at C22 D1 Number Analyzed 68 participants 38 participants
0.0086  (0.0943) 0.0548  (0.1434)
CFB at C23 D1 Number Analyzed 72 participants 35 participants
0.0026  (0.1021) 0.0556  (0.1491)
CFB at C24 D1 Number Analyzed 70 participants 34 participants
0.0104  (0.1008) 0.0506  (0.1570)
CFB at C25 D1 Number Analyzed 68 participants 31 participants
0.0039  (0.1003) 0.0408  (0.1578)
CFB at C26 D1 Number Analyzed 65 participants 30 participants
-0.0017  (0.1101) 0.0463  (0.1443)
CFB at C27 D1 Number Analyzed 62 participants 32 participants
0.0026  (0.1032) 0.0459  (0.1394)
CFB at C28 D1 Number Analyzed 61 participants 31 participants
-0.0013  (0.0965) 0.0419  (0.1490)
CFB at C29 D1 Number Analyzed 59 participants 31 participants
0.0043  (0.1005) 0.0299  (0.1520)
CFB at C30 D1 Number Analyzed 53 participants 32 participants
0.0135  (0.0854) 0.0461  (0.1391)
CFB at C31 D1 Number Analyzed 48 participants 32 participants
0.0052  (0.0887) 0.0399  (0.1484)
CFB at C32 D1 Number Analyzed 49 participants 29 participants
-0.0002  (0.0927) 0.0223  (0.0845)
CFB at C33 D1 Number Analyzed 46 participants 24 participants
0.0082  (0.0803) 0.0243  (0.0695)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments Cycle 2 Day 1 (C2, D1)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.350
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C3, D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.475
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C4, D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.155
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C5, D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.312
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C6 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.674
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments C7 D1
Statistical Test of Hypothesis P-Value 0.398
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C8 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.063
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C9 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.060
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C10 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.957
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments C11 D1
Statistical Test of Hypothesis P-Value 0.245
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments C12 D1
Statistical Test of Hypothesis P-Value 0.205
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C13 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.275
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C14 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.969
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C15 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.546
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C16 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.168
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C17 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.076
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C18 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.348
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C19 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.158
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C20 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.068
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C21 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.057
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C22 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.048
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C23 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C24 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.118
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C25 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.163
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C26 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.078
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C27 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.091
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C28 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.096
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C29 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.341
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C30 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.184
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C31 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.194
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C32 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.288
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C33 D1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.407
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
8.Secondary Outcome
Title Percentage of Participants Experiencing a Clinically Meaningful Change (Improvement, No Change and Deterioration) in the FACIT-Fatigue Scale From Baseline
Hide Description A clinically meaningful improvement or worsening was defined as at least 3 points of improvement or worsening from baseline, respectively, for FACIT-Fatigue. The functional assessment of chronic illness therapy (FACIT-Fatigue Scale V 4.0) is a subscale of the FACIT-F and has been validated in the oncology setting. The FACIT-Fatigue Scale is a short, 13-item, self-administered tool that measures the level of fatigue in an individual during usually daily activities over the past week. The level of fatigue is measured on a 5-point Likert scale (0 = not at all; 4 = very much. The scores range from 0 to 52, with higher scores indicating less fatigue. If there were missing items, but the participant answered at least 50% of the items, then subscores were prorated.
Time Frame Baseline to Cycle 2, Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1C3, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, C23D1, C24D1, C25D1 and continued on day 1 at each cycle through C33D1
Hide Outcome Measure Data
Hide Analysis Population Description
The Health Related Quality of Life (HRQoL) evaluable population was defined as the ITT participants with a non-missing FACIT-Fatigue score at baseline (C1D1) and at least one post-baseline visit. Visits are presented for each post-baseline visit with sample size ≥ 25 in both arms.
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.
Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.
Overall Number of Participants Analyzed 225 219
Measure Type: Number
Unit of Measure: Percentage of Participants
Cycle 2 Day 1 (C2, D1) Improvement Number Analyzed 200 participants 205 participants
32.0 35.6
C2, D1 No Change Number Analyzed 200 participants 205 participants
38.5 40.0
C2, D1 Worsening Number Analyzed 200 participants 205 participants
29.5 24.4
C3, D1 Improvement Number Analyzed 190 participants 183 participants
36.3 35.5
C3, D1 No Change Number Analyzed 190 participants 183 participants
39.5 44.3
C3, D1 Worsening Number Analyzed 190 participants 183 participants
24.2 20.2
C4, D1 Improvement Number Analyzed 185 participants 160 participants
36.8 39.4
C4, D1 No Change Number Analyzed 185 participants 160 participants
36.2 35.6
C4, D1 Worsening Number Analyzed 185 participants 160 participants
27.0 25.0
C5, D1 Improvement Number Analyzed 176 participants 144 participants
35.2 47.2
C5, D1 No Change Number Analyzed 176 participants 144 participants
36.4 30.6
C5, D1 Worsening Number Analyzed 176 participants 144 participants
28.4 22.2
C6, D1 Improvement Number Analyzed 167 participants 128 participants
37.7 38.3
C6, D1 No Change Number Analyzed 167 participants 128 participants
34.1 35.2
C6, D1 Worsening Number Analyzed 167 participants 128 participants
28.1 26.6
C7, D1 Improvement Number Analyzed 152 participants 98 participants
36.2 41.8
C7, D1 No Change Number Analyzed 152 participants 98 participants
36.2 30.6
C7, D1 Worsening Number Analyzed 152 participants 98 participants
27.6 27.6
C8, D1 Improvement Number Analyzed 146 participants 100 participants
39.0 36.0
C8, D1 No Change Number Analyzed 146 participants 100 participants
32.9 40.0
C8, D1 Worsening Number Analyzed 146 participants 100 participants
28.1 24.0
C9, D1 Improvement Number Analyzed 139 participants 87 participants
38.8 35.6
C9, D1 No Change Number Analyzed 139 participants 87 participants
34.5 33.3
C9, D1 Worsening Number Analyzed 139 participants 87 participants
26.6 31.0
C10, D1 Improvement Number Analyzed 130 participants 78 participants
41.5 41.0
C10, D1 No Change Number Analyzed 130 participants 78 participants
31.5 33.3
C10, D1 Worsening Number Analyzed 130 participants 78 participants
26.9 25.6
C11, D1 Improvement Number Analyzed 125 participants 78 participants
36.0 38.5
C11, D1 No Change Number Analyzed 125 participants 78 participants
33.6 35.9
C11, D1 Worsening Number Analyzed 125 participants 78 participants
30.4 25.6
C12, D1 Improvement Number Analyzed 121 participants 71 participants
39.7 43.7
C12, D1 No change Number Analyzed 121 participants 71 participants
32.2 31.0
C12, D1 Worsening Number Analyzed 121 participants 78 participants
28.1 25.4
C13, D1 Improvement Number Analyzed 109 participants 60 participants
37.6 50.0
C13, D1 No Change Number Analyzed 109 participants 60 participants
38.5 28.3
C13, D1 Worsening Number Analyzed 109 participants 60 participants
23.9 21.7
C14, D1 Improvement Number Analyzed 102 participants 62 participants
40.2 40.3
C14, D1 No Change Number Analyzed 102 participants 62 participants
33.3 29.0
C14, D1 Worsening Number Analyzed 102 participants 62 participants
26.5 30.6
C15 D1 Improvement Number Analyzed 96 participants 55 participants
43.8 49.1
C15, D1 No Change Number Analyzed 96 participants 55 participants
35.4 27.3
C15, D1 Worsening Number Analyzed 96 participants 55 participants
20.8 23.6
C16 D1 Improvement Number Analyzed 92 participants 51 participants
38.0 43.1
C16, D1 No Change Number Analyzed 92 participants 51 participants
45.7 29.4
C16, D1 Worsening Number Analyzed 92 participants 51 participants
16.3 27.5
C17 D1 Improvement Number Analyzed 86 participants 47 participants
37.2 42.6
C17, D1 No Change Number Analyzed 86 participants 47 participants
44.2 34.0
C17, D1 Worsening Number Analyzed 86 participants 47 participants
18.6 23.4
C18 D1 Improvement Number Analyzed 87 participants 44 participants
34.5 43.2
C18, D1 No Change Number Analyzed 87 participants 44 participants
39.1 36.4
C18, D1 Worsening Number Analyzed 87 participants 44 participants
26.4 20.5
C19 D1 Improvement Number Analyzed 79 participants 41 participants
40.5 43.9
C19, D1 No Change Number Analyzed 79 participants 41 participants
32.9 31.7
C19, D1 Worsening Number Analyzed 79 participants 41 participants
26.6 24.4
C20 D1 Improvement Number Analyzed 76 participants 40 participants
40.8 50.0
C20, D1 No Change Number Analyzed 76 participants 40 participants
28.9 22.5
C20, D1 Worsening Number Analyzed 76 participants 40 participants
30.3 27.5
C21 D1 Improvement Number Analyzed 75 participants 40 participants
34.7 50.0
C21, D1 No Change Number Analyzed 75 participants 40 participants
42.7 27.5
C21, D1 Worsening Number Analyzed 75 participants 40 participants
22.7 22.5
C22 D1 Improvement Number Analyzed 68 participants 38 participants
35.3 52.6
C22, D1 No Change Number Analyzed 68 participants 38 participants
36.8 26.3
C22, D1 Worsening Number Analyzed 68 participants 38 participants
27.9 21.1
C23 D1 Improvement Number Analyzed 72 participants 35 participants
41.7 48.6
C23, D1 No Change Number Analyzed 72 participants 35 participants
27.8 28.6
C23, D1 Worsening Number Analyzed 72 participants 35 participants
30.6 22.9
C24 D1 Improvement Number Analyzed 70 participants 34 participants
40.0 47.1
C24, D1 No Change Number Analyzed 70 participants 34 participants
28.6 29.4
C24, D1 Worsening Number Analyzed 70 participants 34 participants
31.4 23.5
C25 D1 Improvement Number Analyzed 68 participants 31 participants
38.2 41.9
C25, D1 No Change Number Analyzed 68 participants 31 participants
33.8 32.3
C25, D1 Worsening Number Analyzed 68 participants 31 participants
27.9 25.8
C26 D1 Improvement Number Analyzed 65 participants 30 participants
33.8 46.7
C26, D1 No Change Number Analyzed 65 participants 30 participants
43.1 40.0
C26, D1 Worsening Number Analyzed 65 participants 30 participants
23.1 13.3
C27 D1 Improvement Number Analyzed 62 participants 32 participants
41.9 50.0
C27, D1 No Change Number Analyzed 62 participants 32 participants
30.6 31.3
C27, D1 Worsening Number Analyzed 62 participants 32 participants
27.4 18.8
C28 D1 Improvement Number Analyzed 61 participants 31 participants
47.5 45.2
C28, D1 No Change Number Analyzed 61 participants 31 participants
27.9 38.7
C28, D1 Worsening Number Analyzed 61 participants 31 participants
24.6 16.1
C29 D1 Improvement Number Analyzed 59 participants 31 participants
33.9 51.6
C29, D1 No Change Number Analyzed 59 participants 31 participants
33.9 35.5
C29, D1 Worsening Number Analyzed 59 participants 31 participants
32.2 12.9
C30 D1 Improvement Number Analyzed 53 participants 32 participants
39.6 53.1
C30, D1 No Change Number Analyzed 53 participants 32 participants
41.5 21.9
C30, D1 Worsening Number Analyzed 53 participants 32 participants
18.9 25.0
C31 D1 Improvement Number Analyzed 48 participants 32 participants
39.6 50.0
C31, D1 No Change Number Analyzed 48 participants 32 participants
37.5 34.4
C31, D1 Worsening Number Analyzed 48 participants 32 participants
22.9 15.6
C32 D1 Improvement Number Analyzed 49 participants 29 participants
34.7 65.5
C32, D1 No Change Number Analyzed 49 participants 29 participants
42.9 10.3
C32, D1 Worsening Number Analyzed 49 participants 29 participants
22.4 24.1
C33 D1 Improvement Number Analyzed 46 participants 24 participants
28.3 54.2
C33, D1 No Change Number Analyzed 46 participants 24 participants
45.7 33.3
C33, D1 Worsening Number Analyzed 46 participants 24 participants
26.1 12.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments Cycle 2 Day 1 (C2 D1); Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.391
Comments

The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.

.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.22
Confidence Interval (2-Sided) 95%
0.78 to 1.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C3 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.506
Comments

The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.

.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.18
Confidence Interval (2-Sided) 95%
0.72 to 1.95
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C4 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.719
Comments

The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.

.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.67 to 1.77
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C5 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.186
Comments

The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.

.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.83
Confidence Interval (2-Sided) 95%
0.85 to 2.41
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C6 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.637
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.67 to 1.93
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C7 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.913
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.58 to 1.83
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C8 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.481
Comments

The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.

.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.24
Confidence Interval (2-Sided) 95%
0.68 to 2.24
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C9 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.575
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.46 to 1.54
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C10 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.860
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.55 to 2.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C11 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.433
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.29
Confidence Interval (2-Sided) 95%
0.68 to 2.47
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C12 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.655
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.17
Confidence Interval (2-Sided) 95%
0.59 to 2.35
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C13 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.651
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.55 to 2.61
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C14 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.754
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.44 to 1.80
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C15 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.675
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.38 to 1.88
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C16 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.082
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.48
Confidence Interval (2-Sided) 95%
0.21 to 1.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C17 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.551
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.33 to 1.82
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C18 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.547
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.31
Confidence Interval (2-Sided) 95%
0.54 to 3.19
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C19 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.815
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.46 to 2.68
Estimation Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C20 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.651
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.22
Confidence Interval (2-Sided) 95%
0.52 to 2.88
Estimation Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C21 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.774
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.33 to 2.26
Estimation Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C22 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.359
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.58
Confidence Interval (2-Sided) 95%
0.60 to 4.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C23 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.393
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.49
Confidence Interval (2-Sided) 95%
0.59 to 3.80
Estimation Comments [Not Specified]
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C24 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.418
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.46
Confidence Interval (2-Sided) 95%
0.58 to 3.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C25 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.637
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.27
Confidence Interval (2-Sided) 95%
0.47 to 3.44
Estimation Comments [Not Specified]
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C26 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.279
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.02
Confidence Interval (2-Sided) 95%
0.58 to 7.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C27 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.322
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.72
Confidence Interval (2-Sided) 95%
0.58 to 5.05
Estimation Comments [Not Specified]
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C28 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.256
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.99
Confidence Interval 95%
0.62 to 6.41
Estimation Comments [Not Specified]
Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C29 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.034
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.73
Confidence Interval (2-Sided) 95%
1.08 to 12.92
Estimation Comments [Not Specified]
Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C30 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.477
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.23 to 2.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C31 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.358
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.77
Confidence Interval (2-Sided) 95%
0.53 to 5.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C32 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.993
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
0.33 to 3.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C33 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.177
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.67
Confidence Interval (2-Sided) 95%
0.64 to 11.15
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percentage of Participants Experiencing a Clinically Meaningful Change (Improvement, No Change and Deterioration) in the EQ-5D-3L Scale From Baseline
Hide Description The EQ-5D-3L is a self-administered questionnaire consisting of 5 questions, pertaining to specific health dimensions (ie, mobility, self-care, pain, usual activities, and anxiety/depression) and a health status scale. Each question has 3 levels of severity, corresponding to no problems, moderate problems and severe problems. Canadian population sample weights were used to derive health utility scores. A higher utility score represents a better health state. A clinically meaningful improvement or worsening was defined as at least 0.08 points of improvement or 0.10 points of worsening from baseline, respectively, for the EQ-5D-3L Health Utility Index. The instrument is scored using the United Kingdom (UK) index ranges from -0.594 to 1, where 0 equates to death and 1 equates to full health; -0.594 is considered 'worse than death'.
Time Frame Baseline to Cycle 2, Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1C3, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, C23D1, C24D1, C25D1 and continued on day 1 at each cycle through C33D1
Hide Outcome Measure Data
Hide Analysis Population Description
The Health Related Quality of Life (HRQoL) evaluable population was defined as the ITT participants with a non-missing EQ-5D-3L score at baseline (C1D1) and at least one post-baseline visit. Visits are presented for each post-baseline visit with sample size ≥ 25 in both arms.
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.
Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.
Overall Number of Participants Analyzed 225 217
Measure Type: Number
Unit of Measure: Percentage of Participants
Cycle 2 Day 1 (C2, D1) Improvement Number Analyzed 199 participants 202 participants
10.6 12.9
C2, D1 No Change Number Analyzed 199 participants 202 participants
82.9 78.7
C2, D1 Worsening Number Analyzed 199 participants 202 participants
6.5 8.4
C3, D1 Improvement Number Analyzed 189 participants 183 participants
12.2 13.7
C3, D1 No Change Number Analyzed 189 participants 183 participants
77.8 79.2
C3, D1 Worsening Number Analyzed 189 participants 183 participants
10.1 7.1
C4, D1 Improvement Number Analyzed 183 participants 158 participants
12.6 14.6
C4, D1 No Change Number Analyzed 183 participants 158 participants
79.8 78.5
C4, D1 Worsening Number Analyzed 183 participants 158 participants
7.7 7.0
C5, D1 Improvement Number Analyzed 174 participants 142 participants
13.2 13.4
C5, D1 No Change Number Analyzed 174 participants 142 participants
77.6 77.5
C5, D1 Worsening Number Analyzed 174 participants 142 participants
9.2 9.2
C6, D1 Improvement Number Analyzed 165 participants 126 participants
11.5 15.9
C6, D1 No Change Number Analyzed 165 participants 126 participants
81.8 76.2
C6, D1 Worsening Number Analyzed 165 participants 126 participants
6.7 7.9
C7, D1 Improvement Number Analyzed 150 participants 96 participants
13.3 16.7
C7, D1 No Change Number Analyzed 150 participants 96 participants
77.3 79.2
C7, D1 Worsening Number Analyzed 150 participants 96 participants
9.3 4.2
C8, D1 Improvement Number Analyzed 145 participants 99 participants
13.1 18.2
C8, D1 No Change Number Analyzed 145 participants 99 participants
73.1 74.4
C8, D1 Worsening Number Analyzed 145 participants 99 participants
13.8 7.1
C9, D1 Improvement Number Analyzed 138 participants 85 participants
10.9 15.3
C9, D1 No Change Number Analyzed 138 participants 85 participants
77.5 76.5
C9, D1 Worsening Number Analyzed 138 participants 85 participants
11.6 8.2
C10, D1 Improvement Number Analyzed 130 participants 76 participants
16.9 11.8
C10, D1 No Change Number Analyzed 130 participants 76 participants
72.3 80.3
C10, D1 Worsening Number Analyzed 130 participants 76 participants
10.8 7.9
C11, D1 Improvement Number Analyzed 125 participants 75 participants
16.0 20.0
C11, D1 No Change Number Analyzed 125 participants 75 participants
76.0 73.3
C11, D1 Worsening Number Analyzed 125 participants 75 participants
8.0 6.7
C12, D1 Improvement Number Analyzed 121 participants 68 participants
14.9 13.2
C12, D1 No change Number Analyzed 121 participants 68 participants
75.2 82.4
C12, D1 Worsening Number Analyzed 121 participants 68 participants
9.9 4.4
C13, D1 Improvement Number Analyzed 108 participants 59 participants
17.6 15.3
C13, D1 No Change Number Analyzed 108 participants 59 participants
76.9 78.0
C13, D1 Worsening Number Analyzed 108 participants 59 participants
5.6 6.8
C14, D1 Improvement Number Analyzed 101 participants 61 participants
16.8 14.8
C14, D1 No Change Number Analyzed 101 participants 61 participants
73.3 75.4
C14, D1 Worsening Number Analyzed 101 participants 61 participants
9.9 9.8
C15 D1 Improvement Number Analyzed 96 participants 54 participants
18.8 14.8
C15, D1 No Change Number Analyzed 96 participants 54 participants
72.9 83.3
C15, D1 Worsening Number Analyzed 96 participants 54 participants
8.3 1.9
C16 D1 Improvement Number Analyzed 92 participants 51 participants
17.4 19.6
C16, D1 No Change Number Analyzed 92 participants 51 participants
76.1 76.5
C16, D1 Worsening Number Analyzed 92 participants 51 participants
6.5 3.9
C17 D1 Improvement Number Analyzed 85 participants 46 participants
17.6 26.1
C17, D1 No Change Number Analyzed 85 participants 46 participants
72.9 71.7
C17, D1 Worsening Number Analyzed 85 participants 46 participants
9.4 2.2
C18 D1 Improvement Number Analyzed 87 participants 44 participants
18.4 20.5
C18, D1 No Change Number Analyzed 87 participants 44 participants
71.3 72.7
C18, D1 Worsening Number Analyzed 87 participants 44 participants
10.3 6.8
C19 D1 Improvement Number Analyzed 79 participants 41 participants
17.7 14.6
C19, D1 No Change Number Analyzed 79 participants 41 participants
73.4 80.5
C19, D1 Worsening Number Analyzed 79 participants 41 participants
8.9 4.9
C20 D1 Improvement Number Analyzed 76 participants 40 participants
19.7 20.0
C20, D1 No Change Number Analyzed 76 participants 40 participants
71.1 75.0
C20, D1 Worsening Number Analyzed 76 participants 40 participants
9.2 5.0
C21 D1 Improvement Number Analyzed 75 participants 40 participants
17.3 25.0
C21, D1 No Change Number Analyzed 75 participants 40 participants
74.7 70.0
C21, D1 Worsening Number Analyzed 75 participants 40 participants
8.0 5.0
C22 D1 Improvement Number Analyzed 68 participants 38 participants
16.2 26.3
C22, D1 No Change Number Analyzed 68 participants 38 participants
72.1 71.1
C22, D1 Worsening Number Analyzed 68 participants 38 participants
11.8 2.6
C23 D1 Improvement Number Analyzed 72 participants 35 participants
11.1 22.9
C23, D1 No Change Number Analyzed 72 participants 35 participants
79.2 74.3
C23, D1 Worsening Number Analyzed 72 participants 35 participants
9.7 2.9
C24 D1 Improvement Number Analyzed 70 participants 34 participants
15.7 23.5
C24, D1 No Change Number Analyzed 70 participants 34 participants
74.3 70.6
C24, D1 Worsening Number Analyzed 70 participants 34 participants
10.0 5.9
C25 D1 Improvement Number Analyzed 68 participants 31 participants
16.2 16.1
C25, D1 No Change Number Analyzed 68 participants 31 participants
76.5 77.4
C25, D1 Worsening Number Analyzed 68 participants 31 participants
7.4 6.5
C26 D1 Improvement Number Analyzed 65 participants 30 participants
15.4 23.3
C26, D1 No Change Number Analyzed 65 participants 30 participants
72.3 70.0
C26, D1 Worsening Number Analyzed 65 participants 30 participants
12.3 6.7
C27 D1 Improvement Number Analyzed 62 participants 32 participants
16.1 21.9
C27, D1 No Change Number Analyzed 62 participants 32 participants
71.0 75.0
C27, D1 Worsening Number Analyzed 62 participants 32 participants
12.9 3.1
C28 D1 Improvement Number Analyzed 61 participants 31 participants
11.5 22.6
C28, D1 No Change Number Analyzed 61 participants 31 participants
77.0 71.0
C28, D1 Worsening Number Analyzed 61 participants 31 participants
11.5 6.5
C29 D1 Improvement Number Analyzed 59 participants 31 participants
16.9 22.6
C29, D1 No Change Number Analyzed 59 participants 31 participants
71.2 71.0
C29, D1 Worsening Number Analyzed 59 participants 31 participants
11.9 6.5
C30 D1 Improvement Number Analyzed 53 participants 32 participants
15.1 31.3
C30, D1 No Change Number Analyzed 53 participants 32 participants
75.5 56.3
C30, D1 Worsening Number Analyzed 53 participants 32 participants
9.4 12.5
C31 D1 Improvement Number Analyzed 48 participants 32 participants
14.6 25.0
C31, D1 No Change Number Analyzed 48 participants 32 participants
72.9 62.5
C31, D1 Worsening Number Analyzed 48 participants 32 participants
12.5 12.5
C32 D1 Improvement Number Analyzed 49 participants 29 participants
12.2 13.8
C32, D1 No Change Number Analyzed 49 participants 29 participants
73.5 79.3
C32, D1 Worsening Number Analyzed 49 participants 29 participants
14.3 6.9
C33 D1 Improvement Number Analyzed 46 participants 24 participants
15.2 12.5
C33, D1 No Change Number Analyzed 46 participants 24 participants
78.3 79.2
C33, D1 Worsening Number Analyzed 46 participants 24 participants
6.5 8.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments Cycle 2 Day 1 (C2 D1); Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.487
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.36 to 1.62
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C3 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.378
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.39
Confidence Interval (2-Sided) 95%
0.66 to 2.92
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C4 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.926
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.45 to 2.40
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C5 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.921
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.48 to 2.24
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C6 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.563
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.31 to 1.89
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C7 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.107
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.61
Confidence Interval (2-Sided) 95%
0.80 to 8.45
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C8 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.126
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.05
Confidence Interval (2-Sided) 95%
0.82 to 5.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C9 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.664
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
0.47 to 3.32
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C10 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.583
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.35
Confidence Interval (2-Sided) 95%
0.47 to 3.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C11 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.555
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.40
Confidence Interval (2-Sided) 95%
0.46 to 4.26
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C12 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.153
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.09
Confidence Interval (2-Sided) 95%
0.61 to 15.49
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C13 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.882
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.26 to 4.76
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C14 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.799
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.38 to 3.54
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C15 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.093
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.98
Confidence Interval (2-Sided) 95%
0.65 to 38.37
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C16 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.455
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.88
Confidence Interval (2-Sided) 95%
0.36 to 9.86
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C17 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.126
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.69
Confidence Interval (2-Sided) 95%
0.56 to 39.52
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C18 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.638
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.40
Confidence Interval (2-Sided) 95%
0.35 to 5.68
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C19 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.317
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.27
Confidence Interval (2-Sided) 95%
0.45 to 11.47
Estimation Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C20 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.303
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.25
Confidence Interval (2-Sided) 95%
0.46 to 10.91
Estimation Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C21 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.575
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.58
Confidence Interval (2-Sided) 95%
0.31 to 8.19
Estimation Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C22 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.106
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.06
Confidence Interval (2-Sided) 95%
0.60 to 42.55
Estimation Comments [Not Specified]
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C23 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.185
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.16
Confidence Interval (2-Sided) 95%
0.45 to 38.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C24 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.278
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.79
Confidence Interval (2-Sided) 95%
0.43 to 17.99
Estimation Comments [Not Specified]
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C25 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.920
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.19 to 6.40
Estimation Comments [Not Specified]
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C26 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.551
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.67
Confidence Interval (2-Sided) 95%
0.32 to 8.74
Estimation Comments [Not Specified]
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C27 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.176
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.25
Confidence Interval (2-Sided) 95%
0.47 to 38.29
Estimation Comments [Not Specified]
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C28 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.455
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.92
Confidence Interval (2-Sided) 95%
0.35 to 10.50
Estimation Comments [Not Specified]
Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C29 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.416
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C30 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.693
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.16 to 3.30
Estimation Comments [Not Specified]
Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C31 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.755
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.18 to 3.48
Estimation Comments [Not Specified]
Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C32 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.327
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.34
Confidence Interval (2-Sided) 95%
0.43 to 12.80
Estimation Comments [Not Specified]
Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments C33 D1; Time point as currently entered] comparison of percentage of participants with clinically meaningful worsening.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.612
Comments The common odds ratios (95% CI and p-value) were calculated using CMH tests, stratified by randomization stratification factors to compare the odds of experiencing clinically worsening between CC-486 vs. placebo.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.08 to 4.44
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Time to Definitive Clinically Meaningful Deterioration for ≥ 2 Consecutive Visits as Measured Using the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue Scale V 4.0)
Hide Description Clinically meaningful deterioration was defined as at least 3 points of deterioration from baseline for at least 2 consecutive visits for the FACIT--Fatigue. The FACIT-Fatigue Scale V 4.0) is a subscale of the FACIT-F and has been validated in the oncology setting. The FACIT-Fatigue Scale is a short, 13-item, self-administered tool that measures the level of fatigue in an individual during usually daily activities over the past week. The level of fatigue is measured on a 5-point Likert scale (0 = not at all to 4 = very much. The scores that range from 0 to 52, with higher scores indicating less fatigue. If there were missing items, but the participant answered at least 50% of the items, subscores were prorated.
Time Frame From day 1 (randomization) up to data cut off date of 15 July 2019; approximately 74 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Health Related Quality of Life (HRQoL) evaluable population was defined as the ITT participants with a non-missing FACIT-Fatigue score at baseline (C1D1) and at least one post-baseline visit. Results are presented for each post-baseline visit with sample size ≥ 25 in both arms. Death was censored at the date of the last HRQoL assessment visit.
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.
Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.
Overall Number of Participants Analyzed 225 219
Median (95% Confidence Interval)
Unit of Measure: Weeks
41.1
(28.6 to 84.1)
49.4
(36.6 to 100.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5673
Comments

Stratification factors:

  • Age (at induction therapy): 55 to 64 years and ≥ 65 years
  • Prior history of MDS: yes/no
  • Cytogenetic risk (at induction therapy): intermediate-risk/poor-risk
  • Received consolidation therapy following induction: yes/no
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.0882
Confidence Interval (2-Sided) 95%
0.8146 to 1.4538
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Time to Definitive Clinically Meaningful Deterioration for ≥ 2 Consecutive Visits as Measured Using the EQ-5D HRQoL Scale
Hide Description Clinically meaningful deterioration was defined at least 0.10 point of deterioration from baseline for at least 2 consecutive visits for the EQ-5D Health Utility Index. The EQ-5D-3L is a self-administered questionnaire consisting of 5 questions, pertaining to specific health dimensions (ie, mobility, self-care, pain, usual activities, and anxiety/depression) and a health status scale. Each question has 3 levels of severity, corresponding to no problems, moderate problems and severe problems. Canadian population sample weights were used to derive health utility scores. A higher utility score represents a better health state. A clinically meaningful improvement or worsening was defined as at least 0.08 points of improvement or 0.10 points of worsening from baseline, respectively, for the EQ-5D-3L Health Utility Index. The EQ-5D-3L is scored using the UK index ranges from -0.594 to 1, where 0 equates to death and 1 equates to full health; -0.594 is considered 'worse than death'.
Time Frame From day 1 (randomization) up to data cut off date of 15 July 2019; approximately 74 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Health Related Quality of Life (HRQoL) evaluable population was defined as the ITT participants with a non-missing EQ-5D-3L score at baseline (C1D1) and at least one post-baseline visit. Results are presented for each post-baseline visit with sample size ≥ 25 in both arms. Death was censored at the date of the last HRQoL assessment visit.
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.
Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.
Overall Number of Participants Analyzed 225 217
Median (95% Confidence Interval)
Unit of Measure: Weeks
NA [1] 
(135.1 to NA)
NA [1] 
(122.9 to NA)
[1]
Not estimable because the survival curve does not drop to or below 0.5, i.e. the cumulative probability of developing clinically meaningful deterioration does not reach or exceed 50%, during the observation period
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine Plus Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7522
Comments

Stratification factors:

  • Age (at induction therapy): 55 to 64 years and ≥ 65 years
  • Prior history of MDS: yes/no
  • Cytogenetic risk (at induction therapy): intermediate-risk/poor-risk
  • Received consolidation therapy following induction: yes/no
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.9345
Confidence Interval (2-Sided) 95%
0.6136 to 1.4231
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Healthcare Resource Utilization (HRU): Rate of Hospital Events Per Person Year
Hide Description HRU is defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU is a key component to understand treatment costs and budget impact of new treatments from a provider perspective.
Time Frame Day 1 (randomization) to the date of the data cut off date of 15 July 2019; approximately 74 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population includes all participants who received at least 1 dose of study drug.
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.
Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.
Overall Number of Participants Analyzed 236 233
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Hospitalizations per person-years
0.48
(0.41 to 0.55)
0.64
(0.54 to 0.75)
13.Secondary Outcome
Title Healthcare Resource Utilization (HRU): Number of Days Hospitalized Per Person-Year
Hide Description HRU is defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU is a key component to understand treatment costs and budget impact of new treatments from a provider perspective.
Time Frame Day 1 (randomization) to the date of the data cut off date of 15 July 2019; approximately 74 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population includes all participants who received at least 1 dose of study drug.
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.
Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.
Overall Number of Participants Analyzed 236 233
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Days per person-years
7.89
(7.61 to 8.19)
13.36
(12.90 to 13.84)
Time Frame Day 1 (randomization) to the date of the data cut off date of 15 July 2019; the median treatment duration was 11.6 months (range: 0.5 to 74.3 months) for the oral azacitidine arm and 5.7 months (range: 0.7 to 68.5 months) for the placebo arm.
Adverse Event Reporting Description

Note: Mortality data based off Intent-to-Treat population (all participants who are randomized, regardless of whether they received treatment or not).

Serious AE and non-serious AE data based off Safety population (all randomized participants who have received at least 1 dose of study drug).
 
Arm/Group Title Oral Azacitidine Placebo
Hide Arm/Group Description Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study. Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.
All-Cause Mortality
Oral Azacitidine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   158/238 (66.39%)   171/234 (73.08%) 
Hide Serious Adverse Events
Oral Azacitidine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   79/236 (33.47%)   60/233 (25.75%) 
Blood and lymphatic system disorders     
Anaemia † 1  2/236 (0.85%)  3/233 (1.29%) 
Disseminated intravascular coagulation † 1  0/236 (0.00%)  1/233 (0.43%) 
Febrile neutropenia † 1  16/236 (6.78%)  9/233 (3.86%) 
Lymphadenitis † 1  1/236 (0.42%)  0/233 (0.00%) 
Neutropenia † 1  2/236 (0.85%)  0/233 (0.00%) 
Pancytopenia † 1  0/236 (0.00%)  1/233 (0.43%) 
Thrombocytopenia † 1  2/236 (0.85%)  3/233 (1.29%) 
Thrombocytosis † 1  1/236 (0.42%)  0/233 (0.00%) 
Cardiac disorders     
Acute myocardial infarction † 1  1/236 (0.42%)  1/233 (0.43%) 
Angina pectoris † 1  1/236 (0.42%)  0/233 (0.00%) 
Angina unstable † 1  0/236 (0.00%)  1/233 (0.43%) 
Aortic valve disease † 1  1/236 (0.42%)  0/233 (0.00%) 
Atrial fibrillation † 1  3/236 (1.27%)  0/233 (0.00%) 
Cardiac failure congestive † 1  1/236 (0.42%)  1/233 (0.43%) 
Cardiogenic shock † 1  1/236 (0.42%)  0/233 (0.00%) 
Coronary artery disease † 1  0/236 (0.00%)  1/233 (0.43%) 
Stress cardiomyopathy † 1  0/236 (0.00%)  1/233 (0.43%) 
Congenital, familial and genetic disorders     
Hydrocele † 1  1/236 (0.42%)  0/233 (0.00%) 
Eye disorders     
Iridocyclitis † 1  1/236 (0.42%)  0/233 (0.00%) 
Keratitis † 1  1/236 (0.42%)  0/233 (0.00%) 
Ulcerative keratitis † 1  1/236 (0.42%)  0/233 (0.00%) 
Gastrointestinal disorders     
Abdominal pain † 1  0/236 (0.00%)  1/233 (0.43%) 
Colitis † 1  1/236 (0.42%)  0/233 (0.00%) 
Constipation † 1  1/236 (0.42%)  0/233 (0.00%) 
Crohn's disease † 1  1/236 (0.42%)  0/233 (0.00%) 
Diarrhoea † 1  3/236 (1.27%)  0/233 (0.00%) 
Dysphagia † 1  1/236 (0.42%)  0/233 (0.00%) 
Gastritis † 1  2/236 (0.85%)  0/233 (0.00%) 
Gastroenteritis eosinophilic † 1  0/236 (0.00%)  1/233 (0.43%) 
Gastrointestinal haemorrhage † 1  1/236 (0.42%)  1/233 (0.43%) 
Ileus paralytic † 1  1/236 (0.42%)  0/233 (0.00%) 
Inguinal hernia † 1  1/236 (0.42%)  1/233 (0.43%) 
Lower gastrointestinal haemorrhage † 1  0/236 (0.00%)  1/233 (0.43%) 
Melaena † 1  1/236 (0.42%)  0/233 (0.00%) 
Nausea † 1  1/236 (0.42%)  1/233 (0.43%) 
Neutropenic colitis † 1  1/236 (0.42%)  0/233 (0.00%) 
Pancreatitis acute † 1  1/236 (0.42%)  2/233 (0.86%) 
Small intestinal haemorrhage † 1  1/236 (0.42%)  0/233 (0.00%) 
Upper gastrointestinal haemorrhage † 1  1/236 (0.42%)  0/233 (0.00%) 
Vomiting † 1  2/236 (0.85%)  0/233 (0.00%) 
General disorders     
Asthenia † 1  0/236 (0.00%)  1/233 (0.43%) 
Fatigue † 1  2/236 (0.85%)  1/233 (0.43%) 
General physical health deterioration † 1  0/236 (0.00%)  1/233 (0.43%) 
Multiple organ dysfunction syndrome † 1  1/236 (0.42%)  2/233 (0.86%) 
Pyrexia † 1  6/236 (2.54%)  1/233 (0.43%) 
Hepatobiliary disorders     
Cholecystitis † 1  3/236 (1.27%)  2/233 (0.86%) 
Cholecystitis acute † 1  0/236 (0.00%)  1/233 (0.43%) 
Cholecystitis chronic † 1  0/236 (0.00%)  1/233 (0.43%) 
Cholelithiasis † 1  0/236 (0.00%)  2/233 (0.86%) 
Hyperbilirubinaemia † 1  1/236 (0.42%)  0/233 (0.00%) 
Immune system disorders     
Allergy to vaccine † 1  1/236 (0.42%)  0/233 (0.00%) 
Infections and infestations     
Atypical pneumonia † 1  1/236 (0.42%)  0/233 (0.00%) 
Bacteraemia † 1  1/236 (0.42%)  0/233 (0.00%) 
Bacterial infection † 1  1/236 (0.42%)  0/233 (0.00%) 
Bacterial sepsis † 1  1/236 (0.42%)  0/233 (0.00%) 
Cellulitis † 1  4/236 (1.69%)  1/233 (0.43%) 
Cholecystitis infective † 1  1/236 (0.42%)  0/233 (0.00%) 
Clostridium difficile infection † 1  1/236 (0.42%)  0/233 (0.00%) 
Cystitis † 1  1/236 (0.42%)  0/233 (0.00%) 
Device related infection † 1  1/236 (0.42%)  1/233 (0.43%) 
Device related sepsis † 1  1/236 (0.42%)  0/233 (0.00%) 
Diverticulitis † 1  1/236 (0.42%)  0/233 (0.00%) 
Endophthalmitis † 1  1/236 (0.42%)  0/233 (0.00%) 
Gastroenteritis † 1  2/236 (0.85%)  0/233 (0.00%) 
Gastroenteritis viral † 1  1/236 (0.42%)  0/233 (0.00%) 
Gastrointestinal infection † 1  0/236 (0.00%)  1/233 (0.43%) 
Herpes zoster † 1  1/236 (0.42%)  1/233 (0.43%) 
Influenza † 1  3/236 (1.27%)  0/233 (0.00%) 
Klebsiella sepsis † 1  1/236 (0.42%)  0/233 (0.00%) 
Lung abscess † 1  1/236 (0.42%)  0/233 (0.00%) 
Lung infection † 1  2/236 (0.85%)  1/233 (0.43%) 
Neutropenic sepsis † 1  2/236 (0.85%)  1/233 (0.43%) 
Pneumonia † 1  9/236 (3.81%)  7/233 (3.00%) 
Pneumonia fungal † 1  1/236 (0.42%)  1/233 (0.43%) 
Pseudomonas infection † 1  1/236 (0.42%)  0/233 (0.00%) 
Rectal abscess † 1  1/236 (0.42%)  0/233 (0.00%) 
Respiratory tract infection † 1  0/236 (0.00%)  1/233 (0.43%) 
Salmonellosis † 1  1/236 (0.42%)  0/233 (0.00%) 
Sepsis † 1  4/236 (1.69%)  5/233 (2.15%) 
Septic shock † 1  2/236 (0.85%)  0/233 (0.00%) 
Staphylococcal infection † 1  1/236 (0.42%)  0/233 (0.00%) 
Staphylococcal sepsis † 1  1/236 (0.42%)  0/233 (0.00%) 
Urinary tract infection † 1  1/236 (0.42%)  1/233 (0.43%) 
Urinary tract infection bacterial † 1  1/236 (0.42%)  0/233 (0.00%) 
Urosepsis † 1  1/236 (0.42%)  0/233 (0.00%) 
Wound infection † 1  1/236 (0.42%)  0/233 (0.00%) 
Injury, poisoning and procedural complications     
Cataract traumatic † 1  0/236 (0.00%)  1/233 (0.43%) 
Chemical peritonitis † 1  1/236 (0.42%)  0/233 (0.00%) 
Fall † 1  1/236 (0.42%)  0/233 (0.00%) 
Femoral neck fracture † 1  1/236 (0.42%)  0/233 (0.00%) 
Foot fracture † 1  0/236 (0.00%)  1/233 (0.43%) 
Hip fracture † 1  1/236 (0.42%)  0/233 (0.00%) 
Post-traumatic pain † 1  1/236 (0.42%)  0/233 (0.00%) 
Spinal fracture † 1  1/236 (0.42%)  0/233 (0.00%) 
Subdural haematoma † 1  1/236 (0.42%)  1/233 (0.43%) 
Traumatic intracranial haemorrhage † 1  1/236 (0.42%)  0/233 (0.00%) 
Investigations     
Alanine aminotransferase increased † 1  1/236 (0.42%)  0/233 (0.00%) 
C-reactive protein increased † 1  1/236 (0.42%)  0/233 (0.00%) 
Gamma-glutamyltransferase increased † 1  1/236 (0.42%)  0/233 (0.00%) 
General physical condition abnormal † 1  0/236 (0.00%)  1/233 (0.43%) 
Troponin increased † 1  0/236 (0.00%)  1/233 (0.43%) 
Weight decreased † 1  1/236 (0.42%)  0/233 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  1/236 (0.42%)  0/233 (0.00%) 
Dehydration † 1  1/236 (0.42%)  1/233 (0.43%) 
Hyperkalaemia † 1  2/236 (0.85%)  0/233 (0.00%) 
Hypocalcaemia † 1  1/236 (0.42%)  0/233 (0.00%) 
Hypokalaemia † 1  1/236 (0.42%)  1/233 (0.43%) 
Musculoskeletal and connective tissue disorders     
Back pain † 1  3/236 (1.27%)  0/233 (0.00%) 
Bone pain † 1  0/236 (0.00%)  1/233 (0.43%) 
Intervertebral disc protrusion † 1  1/236 (0.42%)  0/233 (0.00%) 
Joint effusion † 1  0/236 (0.00%)  1/233 (0.43%) 
Myalgia † 1  0/236 (0.00%)  1/233 (0.43%) 
Osteoarthritis † 1  1/236 (0.42%)  0/233 (0.00%) 
Osteoporotic fracture † 1  1/236 (0.42%)  0/233 (0.00%) 
Spinal pain † 1  0/236 (0.00%)  1/233 (0.43%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma † 1  1/236 (0.42%)  3/233 (1.29%) 
Cholangiocarcinoma † 1  0/236 (0.00%)  1/233 (0.43%) 
Endometrial cancer † 1  0/236 (0.00%)  1/233 (0.43%) 
Gliomatosis cerebri † 1  0/236 (0.00%)  1/233 (0.43%) 
Lung adenocarcinoma † 1  1/236 (0.42%)  0/233 (0.00%) 
Malignant melanoma † 1  1/236 (0.42%)  1/233 (0.43%) 
Meningioma † 1  1/236 (0.42%)  0/233 (0.00%) 
Metastases to meninges † 1  1/236 (0.42%)  0/233 (0.00%) 
Prostatic adenoma † 1  1/236 (0.42%)  0/233 (0.00%) 
Squamous cell carcinoma † 1  0/236 (0.00%)  1/233 (0.43%) 
Squamous cell carcinoma of lung † 1  0/236 (0.00%)  1/233 (0.43%) 
Squamous cell carcinoma of skin † 1  1/236 (0.42%)  1/233 (0.43%) 
Nervous system disorders     
Central nervous system inflammation † 1  0/236 (0.00%)  1/233 (0.43%) 
Cerebral haemorrhage † 1  2/236 (0.85%)  1/233 (0.43%) 
Cerebral infarction † 1  0/236 (0.00%)  1/233 (0.43%) 
Cerebral ischaemia † 1  0/236 (0.00%)  1/233 (0.43%) 
Haemorrhage intracranial † 1  1/236 (0.42%)  0/233 (0.00%) 
Ischaemic cerebral infarction † 1  1/236 (0.42%)  0/233 (0.00%) 
Syncope † 1  0/236 (0.00%)  1/233 (0.43%) 
Transient ischaemic attack † 1  1/236 (0.42%)  0/233 (0.00%) 
Psychiatric disorders     
Behaviour disorder † 1  1/236 (0.42%)  0/233 (0.00%) 
Completed suicide † 1  1/236 (0.42%)  0/233 (0.00%) 
Renal and urinary disorders     
Acute kidney injury † 1  1/236 (0.42%)  0/233 (0.00%) 
Ureterolithiasis † 1  0/236 (0.00%)  1/233 (0.43%) 
Respiratory, thoracic and mediastinal disorders     
Asthma † 1  1/236 (0.42%)  0/233 (0.00%) 
Dyspnoea † 1  2/236 (0.85%)  0/233 (0.00%) 
Epistaxis † 1  0/236 (0.00%)  2/233 (0.86%) 
Pneumonia aspiration † 1  1/236 (0.42%)  1/233 (0.43%) 
Pneumonitis † 1  0/236 (0.00%)  1/233 (0.43%) 
Pulmonary embolism † 1  2/236 (0.85%)  0/233 (0.00%) 
Pulmonary haemorrhage † 1  1/236 (0.42%)  0/233 (0.00%) 
Respiratory failure † 1  0/236 (0.00%)  1/233 (0.43%) 
Skin and subcutaneous tissue disorders     
Acute febrile neutrophilic dermatosis † 1  1/236 (0.42%)  0/233 (0.00%) 
Surgical and medical procedures     
Toe amputation † 1  0/236 (0.00%)  1/233 (0.43%) 
Vascular disorders     
Deep vein thrombosis † 1  1/236 (0.42%)  1/233 (0.43%) 
Hypertension † 1  0/236 (0.00%)  1/233 (0.43%) 
Hypotension † 1  0/236 (0.00%)  1/233 (0.43%) 
Peripheral artery stenosis † 1  0/236 (0.00%)  1/233 (0.43%) 
Thrombophlebitis † 1  0/236 (0.00%)  1/233 (0.43%) 
1
Term from vocabulary, MedDRA 22.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Oral Azacitidine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   230/236 (97.46%)   212/233 (90.99%) 
Blood and lymphatic system disorders     
Anaemia † 1  49/236 (20.76%)  42/233 (18.03%) 
Febrile neutropenia † 1  14/236 (5.93%)  10/233 (4.29%) 
Leukopenia † 1  25/236 (10.59%)  19/233 (8.15%) 
Neutropenia † 1  103/236 (43.64%)  61/233 (26.18%) 
Thrombocytopenia † 1  80/236 (33.90%)  62/233 (26.61%) 
Gastrointestinal disorders     
Abdominal pain † 1  31/236 (13.14%)  15/233 (6.44%) 
Abdominal pain upper † 1  21/236 (8.90%)  12/233 (5.15%) 
Constipation † 1  91/236 (38.56%)  56/233 (24.03%) 
Diarrhoea † 1  118/236 (50.00%)  50/233 (21.46%) 
Flatulence † 1  13/236 (5.51%)  4/233 (1.72%) 
Nausea † 1  153/236 (64.83%)  54/233 (23.18%) 
Stomatitis † 1  7/236 (2.97%)  12/233 (5.15%) 
Vomiting † 1  141/236 (59.75%)  23/233 (9.87%) 
General disorders     
Asthenia † 1  44/236 (18.64%)  12/233 (5.15%) 
Fatigue † 1  70/236 (29.66%)  44/233 (18.88%) 
Oedema peripheral † 1  21/236 (8.90%)  24/233 (10.30%) 
Pyrexia † 1  36/236 (15.25%)  43/233 (18.45%) 
Infections and infestations     
Bronchitis † 1  14/236 (5.93%)  9/233 (3.86%) 
Influenza † 1  16/236 (6.78%)  7/233 (3.00%) 
Nasopharyngitis † 1  18/236 (7.63%)  16/233 (6.87%) 
Rhinitis † 1  12/236 (5.08%)  4/233 (1.72%) 
Upper respiratory tract infection † 1  31/236 (13.14%)  32/233 (13.73%) 
Urinary tract infection † 1  16/236 (6.78%)  13/233 (5.58%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  30/236 (12.71%)  15/233 (6.44%) 
Hypokalaemia † 1  20/236 (8.47%)  20/233 (8.58%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  32/236 (13.56%)  24/233 (10.30%) 
Back pain † 1  27/236 (11.44%)  24/233 (10.30%) 
Musculoskeletal pain † 1  14/236 (5.93%)  13/233 (5.58%) 
Pain in extremity † 1  25/236 (10.59%)  12/233 (5.15%) 
Nervous system disorders     
Dizziness † 1  25/236 (10.59%)  21/233 (9.01%) 
Headache † 1  23/236 (9.75%)  26/233 (11.16%) 
Psychiatric disorders     
Anxiety † 1  16/236 (6.78%)  8/233 (3.43%) 
Insomnia † 1  22/236 (9.32%)  23/233 (9.87%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  29/236 (12.29%)  39/233 (16.74%) 
Dyspnoea † 1  13/236 (5.51%)  14/233 (6.01%) 
Epistaxis † 1  15/236 (6.36%)  17/233 (7.30%) 
Oropharyngeal pain † 1  14/236 (5.93%)  19/233 (8.15%) 
Skin and subcutaneous tissue disorders     
Pruritus † 1  12/236 (5.08%)  14/233 (6.01%) 
Vascular disorders     
Hypertension † 1  18/236 (7.63%)  16/233 (6.87%) 
1
Term from vocabulary, MedDRA 22.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results from a center cannot be submitted for publication before results of multicenter study are published unless it is > 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Anne McClain, Senior Manager, Clinical Trial Disclosure
Organization: Celgene Corporation
Phone: 888-260-1599
EMail: clinicaltrialdisclosure@celgene.com
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT01757535    
Other Study ID Numbers: CC-486-AML-001
2012-003457-28 ( EudraCT Number )
First Submitted: November 21, 2012
First Posted: December 31, 2012
Results First Submitted: September 29, 2020
Results First Posted: November 6, 2020
Last Update Posted: January 19, 2024