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

Study of Vidaza Versus Conventional Care Regimens for the Treatment of Acute Myeloid Leukemia (AML)

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: NCT01074047
Recruitment Status : Completed
First Posted : February 24, 2010
Results First Posted : February 26, 2015
Last Update Posted : August 29, 2017
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Acute Myeloid Leukemia
Interventions Drug: Azacitidine
Drug: Conventional Care Regimen
Enrollment 488
Recruitment Details This was a multicenter, international Phase 3 study conducted at 107 investigational sites in 18 countries including South Korea, China, Taiwan, Australia, Canada, United States, Poland, Russia, Czech Republic, Israel, France, Italy, Spain, Germany, United Kingdom, Belgium, Austria and the Netherlands.
Pre-assignment Details  
Arm/Group Title Azacitidine (AZA) Conventional Care Regimens (CCR)
Hide Arm/Group Description Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.

CCRs included:

  • 1 Intensive Chemotherapy: Cytarabine 100-200 mg/m2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m² QD or Idarubicin 9-12 mg/m² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed
  • 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC
  • 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Period Title: Treatment Phase
Started 241 247
Treated Population 236 [1] 240 [2]
Safety Population 236 [3] 235 [3]
Evaluable Population 179 [4] 191 [4]
Completed 24 [5] 13 [5]
Not Completed 217 234
Reason Not Completed
Adverse Event             89             66
Disease Progression             16             21
Withdrawal by Subject             27             48
Death             53             58
Lost to Follow-up             0             1
Protocol Violation             0             1
Miscellaneous             32             39
[1]
5 patients not treated with any drug regimen
[2]
7 patients not treated with any drug regimen
[3]
Received at least one dose of study medication and had at least 1 post dose safety assessment
[4]
Did not meet criteria for exclusion, received ≥1 cycle of treatment and had ≥ 1 efficacy assessment
[5]
Participants who were continuing study treatment at the time of study closure
Period Title: Survival Follow-Up Phase
Started 140 163
Completed 16 27
Not Completed 124 136
Reason Not Completed
Withdrawal by Subject             5             8
Lost to Follow-up             2             1
Death             116             124
Alive at study closure             1             3
Period Title: Extension Phase
Started 22 [1] 0
Safety Population 22 [2] 0
Completed 0 0
Not Completed 22 0
Reason Not Completed
Physician Decision             1             0
Adverse Event             5             0
Disease Progression             9             0
Withdrawal by Subject             2             0
Death             5             0
[1]
2 participants did not enroll in the extension period.
[2]
Participants who enrolled in the extension phase
Arm/Group Title Azacitidine (AZA) Conventional Care Regimens (CCR) Total
Hide Arm/Group Description Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion. #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. Consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed. # 2 Low-dose cytarabine 20 mg SC twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only includes transfusion of blood products, antibiotics, antifungals and nutritional help. Total of all reporting groups
Overall Number of Baseline Participants 241 247 488
Hide Baseline Analysis Population Description
The intent-to-treat (ITT) population is defined as all participants who were randomized, independent of whether they received study treatment or not.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 241 participants 247 participants 488 participants
75.4  (5.60) 75.1  (5.57) 75.2  (5.58)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 241 participants 247 participants 488 participants
<75 years 103 120 223
≥75 years 138 127 265
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 241 participants 247 participants 488 participants
Female
102
  42.3%
98
  39.7%
200
  41.0%
Male
139
  57.7%
149
  60.3%
288
  59.0%
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 241 participants 247 participants 488 participants
0 = Fully Active 54 57 111
1 = Restrictive but Ambulatory 132 132 264
2 = Ambulatory but unable to work 55 58 113
3 = Limited Self Care 0 0 0
4 = Completely disabled 0 0 0
[1]
Measure Description: ECOG performance status is used by doctors and researchers to assess how a participants disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. 0 = Fully Active (Most Favorable Activity), 1 = Restricted activity but ambulatory, 2 = Ambulatory but unable to carry out work activities, 3 = Limited Self Care; 4 = Completely Disabled, No self care (Least Favorable Activity)
World Health Organization Acute Myeloid Leukemia (AML) Classification   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 241 participants 247 participants 488 participants
AML with myelodysplasia-related changes 75 83 158
Therapy-related myeloid neoplasms 8 12 158
AML with recurrent genetic abnormalities 5 9 14
AML not otherwise specified 153 143 296
[1]
Measure Description:

WHO categories include:

  1. Those with AML with recurrent genetic abnormalities. Includes subtypes with multiple chromosome translocations and mutations.
  2. Those with AML with myelodysplasia-related changes. Includes those with prior myelodysplastic syndrome (MDS) or myeloproliferative disease and has transformed to AML.
  3. Those with therapy related myeloid neoplasms and have had prior chemotherapy and/or radiation and subsequently develop AML or MDS
  4. Those with AML not otherwise specified and include subtypes that do not fall into the above categories.
Bone Marrow-Blasts Counts   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of Bone Marrow Blasts
Number Analyzed 241 participants 247 participants 488 participants
66.6  (24.71) 70.2  (22.28) 68.5  (23.56)
[1]
Measure Description: Baseline clinical characteristics, including percentage of bone marrow blasts were assessed centrally and locally. Central values are included here. Baseline blasts were the last non-missing value on or prior to the date of randomization. The bone marrow blasts cells are not typically found in the circulating blood of healthy individuals. Abnormal immature white blood cells (blasts) fill the bone marrow and spill into the bloodstream.
1.Primary Outcome
Title Kaplan-Meier Estimates for Overall Survival
Hide Description Overall Survival was defined as the time from randomization to death from any cause. Overall survival was calculated by the formula: date of death - date of randomization + 1. Participants surviving at the end of the follow-up period or who withdrew consent to follow-up were censored at the date of last contact. Participants who were lost to follow-up were censored at the date last known alive.
Time Frame Day 1 (randomization) to 40 months
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not. Includes participants who died and participants who were censored
Arm/Group Title Azacitidine (AZA) Conventional Care Regimens (CCR)
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 241 247
Median (95% Confidence Interval)
Unit of Measure: months
10.4
(8.0 to 12.7)
6.5
(5.0 to 8.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azacitidine (AZA), Conventional Care Regimens (CCR)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0829
Comments [Not Specified]
Method Log Rank
Comments The p-value is two-sided from an unstratified log-rank test
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.69 to 1.02
Estimation Comments The hazard ratio is from a Cox proportional hazards model stratified by ECOG performance status and cytogenetic risk status.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Azacitidine (AZA), Conventional Care Regimens (CCR)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1009
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.69 to 1.03
Estimation Comments The hazard ratio is from a Cox proportional hazards model stratified by ECOG performance status and cytogenetic risk status.
2.Secondary Outcome
Title One-year Overall Survival Rate
Hide Description Kaplan Meier methods were used to estimate the 1-year survival probabilities for time to death from any cause. Estimates of the 1-year (365 day) survival probabilities and corresponding 95% confidence intervals (CI) were presented by treatment group. The CI for the difference in the 1-year survival probabilities was derived using Greenwoods variance estimate.
Time Frame From Day 1 (randomization) to 40 months
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not. Includes participants who died and participants who were censored
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 241 247
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
46.5
(40.1 to 52.7)
34.3
(28.3 to 40.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azacitidine (AZA), Conventional Care Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 12.26
Confidence Interval (2-Sided) 95%
3.5 to 21.0
Estimation Comments Estimates of the 1-year (365 day) survival probabilities and corresponding 95% confidence intervals (CI) were presented by treatment group. The CI for the difference in the 1-year survival probabilities was derived using Greenwoods variance estimate.
3.Secondary Outcome
Title Event-free Survival (EFS)
Hide Description Event-free survival was defined as the interval from the date of randomization to the date of treatment failure, progressive disease, relapse after complete remission (CR) or complete remission with incomplete blood count recovery (CRi), death from any cause, or lost to follow-up, whichever occurs first. Participants who were still alive without any of these events were censored at the date of their last response assessment.
Time Frame Day 1 (randomization) to date of treatment failure, progressive disease, relapse after Complete Remission (CR) or Complete remission with incomplete blood count recovery (CRi), death from any cause. Day 1 (randomization) to 40 months
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not. Includes participants who died and participants who were censored
Arm/Group Title Azacitidine (AZA) Conventional Care Regimens (CCR)
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 241 247
Median (95% Confidence Interval)
Unit of Measure: months
6.7
(5.0 to 8.8)
4.8
(3.8 to 6.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azacitidine (AZA), Conventional Care Regimens (CCR)
Comments Median is estimated from a Kaplan-Meier distribution of EFS
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1495
Comments [Not Specified]
Method Log Rank
Comments 2 sided unstratified
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.72 to 1.05
Estimation Comments The hazard ratio is from an unstratified Cox proportional hazards model.
4.Secondary Outcome
Title Relapse-Free Survival (RFS) for Participants Who Achieved a Complete Remission (CR) or Complete Remission With Incomplete Blood Count Recovery (CRi)
Hide Description Relapse-free survival was defined as the interval from the date of first documented CR or CRi to the date of relapse, death from any cause, or lost to follow-up, whichever occurred first. Participants who were still alive and in continuous CR or CRi were censored at the date of their last response assessment.
Time Frame Day 1 of first documented CR or CRi to the date of relapse, death from any cause, or lost to follow-up. Day 1 (randomization) to 40 months
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who achieved a CR or CRi
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 67 62
Median (95% Confidence Interval)
Unit of Measure: months
9.3
(6.7 to 12.4)
10.5
(7.3 to 12.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azacitidine (AZA), Conventional Care Regimen
Comments Median is estimated from a Kaplan-Meier distribution of RFS
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5832
Comments [Not Specified]
Method Log Rank
Comments 2 sided unstratified
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.75 to 1.66
Estimation Comments The hazard ratio is from an unstratified Cox proportional hazards model.
5.Secondary Outcome
Title Percentage of Participants Who Achieved a Morphologic CR + CRi as Determined by the Independent Review Committee (IRC) Based on International Working Group (IWG) Response Criteria for Acute Myeloid Leukemia (AML)
Hide Description A complete remission (CR) is defined as a leukemia-free state defined as less than 5% blasts in a BM aspirate with marrow spicules and with at least 200 nucleated cells (there should be no blasts with Auer rods), an absolute neutrophil count (ANC) of ≥ 1 x 10^9/L, a platelet count ≥ 100 x 10^9/L, and transfusion independence (no transfusions for 1 week prior to each assessment). No duration of these findings is required for confirmation of this response. A CR with incomplete blood count recovery (CRi) is defined as <5% BM blasts with the ANC count < 1 x 10^9/L and/or the platelet count may be < 100 x 10^9/L. Where the date of the hematology assessment used is the earliest on or following the date of the BM sample up to 8 days after the BM date.
Time Frame Day 1 (randomization) to 40 months
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not. Includes participants who died and participants who were censored
Arm/Group Title Azacitidine (AZA) Conventional Care Regimens (CCR)
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 241 247
Measure Type: Number
Unit of Measure: percentage of participants
27.8 25.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azacitidine (AZA), Conventional Care Regimens (CCR)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5384
Comments [Not Specified]
Method Fisher Exact
Comments P-value is from Fishers exact test
6.Secondary Outcome
Title Duration of Remission Assessed by the IRC Based on Kaplan-Meier Estimates
Hide Description The time from the date CR or CRi was first documented until the date of documented relapse from CR/CRi. Duration of remission was defined only for those participants who achieved a CR or CRi, as determined by the IRC. Participants who were lost to follow-up without documented relapse, or were alive at last follow-up without documented relapse were censored at the date of their last response assessment.
Time Frame Day 1 (randomization) to 40 months; date of the first documented CR or CRi until date of first documented relapse.
Hide Outcome Measure Data
Hide Analysis Population Description
Includes those who achieved a CR or CRi and assessed by the IRC; numbers of ITT participants in each treatment group
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 67 62
Median (95% Confidence Interval)
Unit of Measure: months
10.4
(7.2 to 15.2)
12.3
(9.0 to 17.0)
7.Secondary Outcome
Title Number of Participants Who Achieved a Cytogenetic Complete Response (CRc-10) as Determined by the IRC.
Hide Description The CRc is a normal karyotype defined as no clonal abnormalities after review of at least 10 metaphases using conventional cytogenetic techniques. Cytogenetic complete remission rate (CRc) is when the following criteria are met: 1) CR criteria met and 2) an abnormal karyotype is present at baseline and 3) there is reversion to normal karyotype at the time of CR (based on ≥ 10 metaphases), where date of cytogenetic sample = date of BM sample used for the CR assessment
Time Frame Day 1 (randomization) to 40 months
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) population was defined as all participants who were randomized, independent of whether they received study treatment or not. Includes participants who died and participants who were censored
Arm/Group Title Azacitidine (AZA) Conventional Care Regimens (CCR)
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 241 247
Measure Type: Number
Unit of Measure: participants
5 15
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azacitidine (AZA), Conventional Care Regimens (CCR)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0376
Comments [Not Specified]
Method Fisher Exact
Comments P-value is from Fishers exact test
8.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description AEs = any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, regardless of cause. Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death
Time Frame Day 1 (randomization) up to last visit completed; final data cut off of 28 Feb 2017
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population = all randomized participants who received at least 1 dose of study drug and had 1 post-dose safety assessment. Because the BSC only regimen consisted of blood products or antibiotics given as needed, those assigned to BSC only were included in the safety population if they had at least 1 post-randomization safety assessment.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen #3 Best Supportive Care Only Conventional Care Regimen #2 Low-dose Cytarabine Conventional Care Regimen #1 Intensive Chemotherapy
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
Best supportive care included red blood cell (RBC) or whole blood transfusions, fresh frozen plasma transfusions, platelet transfusions, antibiotic and/or antifungal therapy, and nutritional support.
Low-dose cytarabine 20 mg SC injection twice a day (BID) for 10 days, every 28 days (optimally for at least 4 cycles) until the end of the study, unless participants were discontinued from the treatment. Best supportive care as needed, including antibiotics and transfusions, per physicians discretion.
Induction Therapy included Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (IV) for 7 days plus daunorubicin 45 to 60 mg/m^² daily IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV daily for 3 days as an alternative to daunorubicin (Cycle 1). Consolidation Therapy (Cycle 2 and 3) Cytarabine 100-200 mg/m^2 as a continuous IV infusion for a total of 3 to 7 days plus daunorubicin 45 to 60 mg/m^² daily or Idarubicin 9-12 mg/m^² IV daily on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from commencement of induction therapy, upon recovery of absolute neutrophil count (ANC) to at least 1.0 x 10^9/L and platelets to at least 75 x 10^9/L. The second consolidation cycle, if given, started between Day 28 and Day 70 from commencement of the first consolidation therapy. Participants could receive BSC as needed, including antibiotics and transfusions, physicians discretion.
Overall Number of Participants Analyzed 236 40 153 42
Measure Type: Number
Unit of Measure: participants
At least one Treatment Emergent AE 234 36 153 42
At least one TEAE related to study drug 188 0 124 39
Grade 3-4 adverse event 207 26 141 37
Grade 3-4 adverse event related to any study drug 125 0 90 29
At least one Grade 5 (leading to death) TEAE 56 23 38 9
Grade 5 adverse event related to any study drug 12 0 10 4
Serious TEAE 188 30 118 27
Serious TEAE related to any study drug 87 0 56 14
TEAE leading to discontinuation of study drug 110 0 68 11
Study drug-related TEAE leading to discontinuation 22 0 20 5
TEAE leading to study drug dose reduction 8 0 2 2
TEAE leading to study drug dose interruption 116 0 61 4
TEAE causing study drug dose reduction/disruption 13 0 7 0
9.Secondary Outcome
Title Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).
Time Frame Baseline to Cycle 3; at approximately 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimens (CCR)
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 135 101
Mean (Standard Deviation)
Unit of Measure: units on a scale
-1.5  (24.69) -1.9  (27.54)
10.Secondary Outcome
Title Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).
Time Frame Baseline to Cycle 5, at approximately 5 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimens (CCR)
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 112 66
Mean (Standard Deviation)
Unit of Measure: units on a scale
-2.8  (27.36) -7.1  (27.61)
11.Secondary Outcome
Title Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).
Time Frame Baseline to Cycle 7, at approximately 7 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimens (CCR)
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 94 53
Mean (Standard Deviation)
Unit of Measure: units on a scale
-6.1  (26.90) -12.2  (30.45)
12.Secondary Outcome
Title Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).
Time Frame Baseline to Cycle 9, at approximately 9 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population. .
Arm/Group Title Azacitidine (AZA) Conventional Care Regimens (CCR)
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 80 36
Mean (Standard Deviation)
Unit of Measure: units on a scale
-9.0  (27.90) -10.2  (33.85)
13.Secondary Outcome
Title Health Related Quality of Life (HRQoL): Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Fatigue Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Fatigue Scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate reduction in fatigue (i.e. improvement in symptom) and positive values indicate increases in fatigue (i.e. worsening of symptom).
Time Frame Baseline to End of Study; at approximately 11-12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimens (CCR)
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 87 80
Mean (Standard Deviation)
Unit of Measure: units on a scale
8.9  (33.54) 6.1  (34.19)
14.Secondary Outcome
Title HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).
Time Frame Baseline to Cycle 3, at approximately 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 136 101
Mean (Standard Deviation)
Unit of Measure: units on a scale
5.1  (26.88) -1.7  (30.69)
15.Secondary Outcome
Title HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).
Time Frame Baseline to Cycle 5, at approximately 5 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 112 66
Mean (Standard Deviation)
Unit of Measure: units on a scale
3.9  (27.49) -6.6  (28.18)
16.Secondary Outcome
Title HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).
Time Frame Baseline to Cycle 7, at approximately 7 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 94 53
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.4  (29.93) -8.8  (28.61)
17.Secondary Outcome
Title HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).
Time Frame Baseline to Cycle 9, at approximately 9 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population. The analysis included 157 from the azacitidine group and 134 in the CCR group, a smaller number than the ITT population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 81 36
Mean (Standard Deviation)
Unit of Measure: units on a scale
-4.9  (26.93) -2.8  (26.87)
18.Secondary Outcome
Title HRQoL: Change From Baseline in the EORTC QLQ-C30 Dyspnea
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Dyspnea scale is scored between 0 and 100, with a high score indicating a higher level of symptoms. Negative change from Baseline values indicate decreased dyspnea (i.e. improvement in symptom) and positive values indicate increased dyspnea (i.e. worsening of symptom).
Time Frame Baseline to end of study, at approximately 11-12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 87 80
Mean (Standard Deviation)
Unit of Measure: units on a scale
12.6  (31.43) 6.3  (35.22)
19.Secondary Outcome
Title HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 PhysicalFunctioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time Frame Baseline to Cycle 3, at approximately 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 136 102
Mean (Standard Deviation)
Unit of Measure: units on a scale
-4.2  (17.98) -0.3  (18.85)
20.Secondary Outcome
Title HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 PhysicalFunctioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time Frame Baseline to Cycle 5, at approximately 5 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 112 67
Mean (Standard Deviation)
Unit of Measure: units on a scale
-4.4  (19.25) -1.3  (20.41)
21.Secondary Outcome
Title HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 PhysicalFunctioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time Frame Baseline to Cycle 7, at approximately 7 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 94 54
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.6  (18.75) 1.5  (23.08)
22.Secondary Outcome
Title HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 PhysicalFunctioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time Frame Baseline to Cycle 9, at approximately 9 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 81 36
Mean (Standard Deviation)
Unit of Measure: units on a scale
3.5  (18.26) -0.4  (22.81)
23.Secondary Outcome
Title HRQoL: Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 PhysicalFunctioning Scale is scored between 0 and 100, with a high score indicating better functioning. Negative change from Baseline values indicate deterioration in functioning and positive values indicate improvement.
Time Frame Baseline to end of study, at approximately 11-12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 87 81
Mean (Standard Deviation)
Unit of Measure: units on a scale
-13.0  (26.74) -9.4  (26.43)
24.Secondary Outcome
Title HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.
Time Frame Baseline to Cycle 3, at approximately 3 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 134 101
Mean (Standard Deviation)
Unit of Measure: units on a scale
0.9  (20.97) 3.8  (26.42)
25.Secondary Outcome
Title HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.
Time Frame Baseline to Cycle 5, at approximately 5 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 112 66
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.6  (22.50) 9.0  (24.82)
26.Secondary Outcome
Title HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.
Time Frame Baseline to Cycle 7, at approximately 7 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 94 52
Mean (Standard Deviation)
Unit of Measure: units on a scale
5.1  (25.84) 8.7  (27.91)
27.Secondary Outcome
Title HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.
Time Frame Baseline to Cycle 9, at approximately 9 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 80 36
Mean (Standard Deviation)
Unit of Measure: units on a scale
7.8  (27.28) 10.4  (23.09)
28.Secondary Outcome
Title HRQoL: Change From Baseline in the EORTC QLQ-C30 Global Health Status-/Quality of Life Domain
Hide Description The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) questionnaire (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale is scored between 0 and 100, with a high score indicating better Global Health Status/QOL. Negative change from Baseline values indicate deterioration in Global Health Status/QOL and positive values indicate improvement.
Time Frame Baseline to end of study, at approximately 11-12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL Evaluable population included only participants with a baseline QoL assessment and at least 1 follow-up assessment. Time windows were applied post-hoc to increase the size of the analyzable population.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 87 80
Mean (Standard Deviation)
Unit of Measure: units on a scale
-4.4  (29.20) -6.1  (27.90)
29.Secondary Outcome
Title Healthcare Resource Utilization (HRU): Number of Inpatient Hospitalizations
Hide Description HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU Analysis may help in evaluating potential costs and budget impact of new treatments from a payer perspective.
Time Frame Day 1 (randomization) to 40 months
Hide Outcome Measure Data
Hide Analysis Population Description
HRU was analyzed for the HRQoL Evaluable Population, a smaller sample than either the ITT population or safety population. Duration of therapy differed between treatment groups. Rate-per-patient year values adjust for these differences.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimens (CCR)
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 157 134
Measure Type: Number
Unit of Measure: participants
139 111
30.Secondary Outcome
Title Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Per Year
Hide Description HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU Analysis may help in evaluating potential costs and budget impact of new treatments from a payer perspective. The rate of inpatient hospitalizations per patient year was calculated as the total number of hospitalizations divided by the total number of patient-years followed in the study period. Patient-years (PY) were calculated as the duration from baseline to last available HRQL assessment for each patient.
Time Frame Day 1 (randomization) to 40 months
Hide Outcome Measure Data
Hide Analysis Population Description
HRU was analyzed for the HRQoL Evaluable Population, a smaller sample than either the ITT population or safety population. Duration of therapy differed between treatment groups. Rate-per-patient year values adjust for these differences.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimens (CCR)
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 157 134
Measure Type: Number
Unit of Measure: hospitalizations per patient year
7.95 4.82
31.Secondary Outcome
Title HRU: Number of Participants Receiving Transfusions
Hide Description Count of study participants who had transfusions during the treatment phase. HRU is defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU Analysis may help in evaluating potential costs and budget impact of new treatments from a payer perspective.
Time Frame Day 1 (randomization) to 40 months
Hide Outcome Measure Data
Hide Analysis Population Description
HRU was analyzed for the HRQoL Evaluable Population, a smaller sample than either the ITT population or safety population. Duration of therapy differed between treatment groups. Rate-per-patient year values adjust for these differences.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 157 134
Measure Type: Number
Unit of Measure: participants
154 134
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Azacitidine (AZA), Conventional Care Regimen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0721
Comments [Not Specified]
Method negative binomial regression analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Relative Ratio
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.62 to 1.02
Estimation Comments [Not Specified]
32.Secondary Outcome
Title HRU: Rate of Transfusions Per Patient Year
Hide Description HRU is defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU Analysis may help in evaluating potential costs and budget impact of new treatments from a payer perspective. The rate of transfusions per patient year was calculated as the total number of transfusions divided by the total number of patient-years followed in the study period. Patient-years (PY) were calculated as the duration from baseline to last available HRQL assessment for each patient.
Time Frame Day 1 (randomization) to 40 months
Hide Outcome Measure Data
Hide Analysis Population Description
HRU was analyzed for the HRQoL Evaluable Population, a smaller sample than either the ITT population or safety population. Duration of therapy differed between treatment groups. Rate-per-patient year values adjust for these differences.
Arm/Group Title Azacitidine (AZA) Conventional Care Regimen
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
CCRs included: #1 Intensive Chemotherapy: Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed # 2 Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC # 3 BSC only = transfusion of blood products, antibiotics, antifungals and nutritional help
Overall Number of Participants Analyzed 157 134
Measure Type: Number
Unit of Measure: transfusions per patient year
34.23 36.04
33.Secondary Outcome
Title Number of Participants in the Extension Phase With Treatment Emergent Adverse Events (TEAEs)
Hide Description AEs = any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, regardless of cause. Serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death
Time Frame From the date of informed consent for the Extension Phase through to the date of last dose of study drug + 28 days up to last visit completed 24 July 2016; maximum duration of exposure to Azacitidine was 871 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population includes those enrolled in the extension phase who received at least one dose of study drug.
Arm/Group Title Azacitidine (AZA)
Hide Arm/Group Description:
Azacitidine 75 mg/m2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
Overall Number of Participants Analyzed 22
Measure Type: Number
Unit of Measure: participants
At least one Treatment Emergent AE 20
At least one TEAE related to study drug 13
At least one Grade 3-4 adverse event 13
At least 1 Grade 3-4 TEAE related to study drug 7
At least 1 Grade 5 TEAE 4
At least 1 Grade 5 TEAE related to study drug 0
At least 1 serious TEAE 10
At least 1 serious TEAE related to study drug 1
At least one serious Grade 3-4 TEAE 8
TEAE leading to discontinuation of study drug 3
Study drug-related TEAE leading to discontinuation 1
TEAE leading to study drug dose reduction 1
TEAE leading to study drug dose interruption only 17
TEAE causing study dose reduction/interruption 2
Time Frame From first dose to 1) last dose + 28 days for azacitidine and low-dose cytarabine; 2) last dose + 70 days for intensive chemotherapy; 3) discontinuation for BSC only. Median duration was 191.5, 65.0, 125.0, 124.5 and 360.0 days for each group respectively
Adverse Event Reporting Description

3) discontinuation for BSC only. Median duration was 191.5, 65.0, 125.0, 124.5 and 360.0 days for each group respectively.

AEs reported for the Azacitidine group are those that occurred in the treatment phase, AEs reported in the Azacitidine extension group occurred during extension phase
 
Arm/Group Title Azacitidine BSC Only Low-dose Cytarabine Intensive Chemotherapy Azacitidine-extension
Hide Arm/Group Description Azacitidine 75 mg/m^2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion Transfusion of blood products, antibiotics, antifungals and nutritional help Low-dose cytarabine 20 mg subcutaneously twice a day (BID) for 10 days every 28 days, plus BSC Cytarabine 100-200 mg/m^2 as a continuous intravenous infusion (CIVI) for 7 days and daunorubicin 45 to 60 mg/m^² daily (QD) IV on Days 1, 2 and 3 or Idarubicin 9-12 mg/m^² IV QD for 3 days. Consolidation Therapy (Cycle 2 and 3) = Cytarabine 100-200 mg/m^2 as a CIVI for 3 to 7 days and daunorubicin 45 to 60 mg/m^² QD or Idarubicin 9-12 mg/m^² IV QD on Days 1 and 2. The first consolidation therapy started between Day 28 and Day 70 from start of induction therapy, upon recovery of absolute neutrophil count (ANC) above 1.0 x 10^9/L and platelets above 75 x 10^9/L. The second cycle started between Day 28 and Day 70 from start of first consolidation therapy. Best supportive care (BSC) of antibiotics and transfusions, were given as needed Azacitidine 75 mg/m^2/day by subcutaneous injection [SC] for 7 days every 28 days, with a 21 day rest period (optimally for at least 6 cycles) plus best supportive care as needed, including antibiotics and blood product transfusions, growth factors, per physician's discretion.
All-Cause Mortality
Azacitidine BSC Only Low-dose Cytarabine Intensive Chemotherapy Azacitidine-extension
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Azacitidine BSC Only Low-dose Cytarabine Intensive Chemotherapy Azacitidine-extension
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   188/236 (79.66%)   30/40 (75.00%)   118/153 (77.12%)   27/42 (64.29%)   10/22 (45.45%) 
Blood and lymphatic system disorders           
AGRANULOCYTOSIS † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
ANAEMIA † 1  10/236 (4.24%)  1/40 (2.50%)  11/153 (7.19%)  0/42 (0.00%)  1/22 (4.55%) 
DISSEMINATED INTRAVASCULAR COAGULATION † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
FEBRILE BONE MARROW APLASIA † 1  2/236 (0.85%)  0/40 (0.00%)  3/153 (1.96%)  0/42 (0.00%)  0/22 (0.00%) 
FEBRILE NEUTROPENIA † 1  59/236 (25.00%)  12/40 (30.00%)  38/153 (24.84%)  7/42 (16.67%)  4/22 (18.18%) 
LEUKOCYTOSIS † 1  4/236 (1.69%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
LEUKOPENIA † 1  1/236 (0.42%)  0/40 (0.00%)  2/153 (1.31%)  0/42 (0.00%)  0/22 (0.00%) 
LYMPHADENOPATHY † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
NEUTROPENIA † 1  5/236 (2.12%)  1/40 (2.50%)  3/153 (1.96%)  1/42 (2.38%)  0/22 (0.00%) 
PANCYTOPENIA † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
THROMBOCYTOPENIA † 1  6/236 (2.54%)  0/40 (0.00%)  14/153 (9.15%)  0/42 (0.00%)  0/22 (0.00%) 
THROMBOTIC THROMBOCYTOPENIC PURPURA † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
Cardiac disorders           
ACUTE CORONARY SYNDROME † 1  2/236 (0.85%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
ACUTE LEFT VENTRICULAR FAILURE † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
ACUTE MYOCARDIAL INFARCTION † 1  3/236 (1.27%)  0/40 (0.00%)  0/153 (0.00%)  1/42 (2.38%)  0/22 (0.00%) 
ANGINA PECTORIS † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  1/22 (4.55%) 
ATRIAL FIBRILLATION † 1  7/236 (2.97%)  1/40 (2.50%)  3/153 (1.96%)  2/42 (4.76%)  0/22 (0.00%) 
CARDIAC ARREST † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
CARDIAC FAILURE † 1  2/236 (0.85%)  0/40 (0.00%)  1/153 (0.65%)  1/42 (2.38%)  0/22 (0.00%) 
CARDIAC FAILURE ACUTE † 1  0/236 (0.00%)  0/40 (0.00%)  0/153 (0.00%)  1/42 (2.38%)  0/22 (0.00%) 
CARDIAC FAILURE CONGESTIVE † 1  0/236 (0.00%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
CARDIO-RESPIRATORY ARREST † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
CARDIOVASCULAR INSUFFICIENCY † 1  1/236 (0.42%)  0/40 (0.00%)  2/153 (1.31%)  1/42 (2.38%)  0/22 (0.00%) 
ISCHAEMIC CARDIOMYOPATHY † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
LEFT VENTRICULAR FAILURE † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
MYOCARDIAL INFARCTION † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  1/22 (4.55%) 
PERICARDIAL EFFUSION † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  1/42 (2.38%)  0/22 (0.00%) 
PERICARDITIS † 1  1/236 (0.42%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
SUPRAVENTRICULAR TACHYCARDIA † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
VENTRICULAR TACHYCARDIA † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
Eye disorders           
CATARACT † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
CONJUNCTIVAL HAEMORRHAGE † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
Gastrointestinal disorders           
ABDOMINAL PAIN † 1  1/236 (0.42%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  1/22 (4.55%) 
ABDOMINAL PAIN LOWER † 1  0/236 (0.00%)  0/40 (0.00%)  2/153 (1.31%)  0/42 (0.00%)  0/22 (0.00%) 
ANAL HAEMORRHAGE † 1  0/236 (0.00%)  1/40 (2.50%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
ASCITES † 1  0/236 (0.00%)  0/40 (0.00%)  0/153 (0.00%)  1/42 (2.38%)  0/22 (0.00%) 
COLITIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
CONSTIPATION † 1  0/236 (0.00%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  1/22 (4.55%) 
DIARRHOEA † 1  4/236 (1.69%)  0/40 (0.00%)  4/153 (2.61%)  0/42 (0.00%)  0/22 (0.00%) 
DIVERTICULUM INTESTINAL † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
DUODENAL ULCER HAEMORRHAGE † 1  0/236 (0.00%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  1/22 (4.55%) 
DYSPHAGIA † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
ENTERITIS † 1  0/236 (0.00%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
ENTEROCOLITIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
GASTRITIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
GASTROINTESTINAL HAEMORRHAGE † 1  1/236 (0.42%)  1/40 (2.50%)  4/153 (2.61%)  0/42 (0.00%)  0/22 (0.00%) 
HAEMATEMESIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
ILEUS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
INTESTINAL ISCHAEMIA † 1  0/236 (0.00%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  1/22 (4.55%) 
INTESTINAL OBSTRUCTION † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
MELAENA † 1  1/236 (0.42%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
MOUTH HAEMORRHAGE † 1  1/236 (0.42%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
NAUSEA † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
RECTAL HAEMORRHAGE † 1  1/236 (0.42%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
RECTAL ULCER † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
STOMATITIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  1/22 (4.55%) 
UPPER GASTROINTESTINAL HAEMORRHAGE † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
VOMITING † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
General disorders           
ASTHENIA † 1  4/236 (1.69%)  1/40 (2.50%)  3/153 (1.96%)  0/42 (0.00%)  0/22 (0.00%) 
CHEST PAIN † 1  0/236 (0.00%)  0/40 (0.00%)  2/153 (1.31%)  1/42 (2.38%)  0/22 (0.00%) 
CHILLS † 1  1/236 (0.42%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
DEATH † 1  3/236 (1.27%)  0/40 (0.00%)  2/153 (1.31%)  0/42 (0.00%)  0/22 (0.00%) 
FATIGUE † 1  3/236 (1.27%)  0/40 (0.00%)  1/153 (0.65%)  1/42 (2.38%)  0/22 (0.00%) 
GENERAL PHYSICAL HEALTH DETERIORATION † 1  1/236 (0.42%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
HYPERTHERMIA † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
INJECTION SITE EXTRAVASATION † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
INJECTION SITE REACTION † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
MALAISE † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
MULTI-ORGAN FAILURE † 1  1/236 (0.42%)  0/40 (0.00%)  2/153 (1.31%)  0/42 (0.00%)  0/22 (0.00%) 
OEDEMA PERIPHERAL † 1  0/236 (0.00%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
PAIN † 1  1/236 (0.42%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
PYREXIA † 1  25/236 (10.59%)  3/40 (7.50%)  16/153 (10.46%)  2/42 (4.76%)  0/22 (0.00%) 
SUDDEN CARDIAC DEATH † 1  1/236 (0.42%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
SUDDEN DEATH † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
Hepatobiliary disorders           
CHOLANGITIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
CHOLECYSTITIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
CHOLECYSTITIS ACUTE † 1  1/236 (0.42%)  0/40 (0.00%)  1/153 (0.65%)  1/42 (2.38%)  0/22 (0.00%) 
CHOLELITHIASIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
HEPATIC FAILURE † 1  0/236 (0.00%)  0/40 (0.00%)  2/153 (1.31%)  0/42 (0.00%)  0/22 (0.00%) 
HYPERBILIRUBINAEMIA † 1  0/236 (0.00%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  1/22 (4.55%) 
Immune system disorders           
ANAPHYLACTIC SHOCK † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
Infections and infestations           
ABSCESS NECK † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
ABSCESS SOFT TISSUE † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
ACUTE SINUSITIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
AEROMONA INFECTION † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
ANAL ABSCESS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
APPENDICITIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
ARTHRITIS INFECTIVE † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
ASPERGILLUS INFECTION † 1  0/236 (0.00%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
BACTERAEMIA † 1  2/236 (0.85%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  1/22 (4.55%) 
BRONCHITIS † 1  3/236 (1.27%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
BRONCHOPNEUMONIA † 1  4/236 (1.69%)  1/40 (2.50%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
BRONCHOPULMONARY ASPERGILLOSIS † 1  3/236 (1.27%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  1/22 (4.55%) 
CANDIDA INFECTION † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
CELLULITIS † 1  5/236 (2.12%)  4/40 (10.00%)  3/153 (1.96%)  1/42 (2.38%)  0/22 (0.00%) 
CELLULITIS ORBITAL † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
CLOSTRIDIUM DIFFICILE COLITIS † 1  2/236 (0.85%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
CLOSTRIDIUM DIFFICILE INFECTION † 1  1/236 (0.42%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
CORYNEBACTERIUM SEPSIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
CYSTITIS † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
DEVICE RELATED INFECTION † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
DEVICE RELATED SEPSIS † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
DIVERTICULITIS † 1  4/236 (1.69%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
ENTEROBACTER PNEUMONIA † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
ENTEROCOCCAL BACTERAEMIA † 1  0/236 (0.00%)  1/40 (2.50%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
ENTEROCOCCAL SEPSIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
EPIGLOTTITIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
ERYSIPELAS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
ESCHERICHIA BACTERAEMIA † 1  3/236 (1.27%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
ESCHERICHIA INFECTION † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
ESCHERICHIA SEPSIS † 1  4/236 (1.69%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
FURUNCLE † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
GASTROENTERITIS † 1  1/236 (0.42%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
GASTROENTERITIS CLOSTRIDIAL † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
GASTROINTESTINAL FUNGAL INFECTION † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
GROIN ABSCESS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
HERPES ZOSTER † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
INFECTED CYST † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
INFECTION † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  1/22 (4.55%) 
INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
KLEBSIELLA BACTERAEMIA † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
KLEBSIELLA SEPSIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
LIVER ABSCESS † 1  0/236 (0.00%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  1/22 (4.55%) 
LOBAR PNEUMONIA † 1  2/236 (0.85%)  0/40 (0.00%)  2/153 (1.31%)  0/42 (0.00%)  0/22 (0.00%) 
LOWER RESPIRATORY TRACT INFECTION † 1  1/236 (0.42%)  1/40 (2.50%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
LUNG ABSCESS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
LUNG INFECTION † 1  2/236 (0.85%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
MUMPS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
NASOPHARYNGITIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
NEUTROPENIC SEPSIS † 1  7/236 (2.97%)  2/40 (5.00%)  4/153 (2.61%)  1/42 (2.38%)  0/22 (0.00%) 
ORAL CANDIDIASIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
OROPHARYNGITIS FUNGAL † 1  0/236 (0.00%)  0/40 (0.00%)  0/153 (0.00%)  1/42 (2.38%)  0/22 (0.00%) 
PARAINFLUENZAE VIRUS INFECTION † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
PERIORBITAL CELLULITIS † 1  0/236 (0.00%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
PERIRECTAL ABSCESS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
PERITONITIS † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
PHARYNGITIS † 1  2/236 (0.85%)  0/40 (0.00%)  2/153 (1.31%)  0/42 (0.00%)  0/22 (0.00%) 
PHARYNGOTONSILLITIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
PNEUMONIA † 1  48/236 (20.34%)  3/40 (7.50%)  29/153 (18.95%)  3/42 (7.14%)  2/22 (9.09%) 
PNEUMONIA FUNGAL † 1  3/236 (1.27%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
PNEUMONIA KLEBSIELLA † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
PNEUMONIA MYCOPLASMAL † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
PNEUMONIA PARAINFLUENZAE VIRAL † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
PNEUMONIA PSEUDOMONAS AERUGINOSA † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
PNEUMONIA STAPHYLOCOCCAL † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
PNEUMONIA STREPTOCOCCAL † 1  0/236 (0.00%)  0/40 (0.00%)  0/153 (0.00%)  1/42 (2.38%)  0/22 (0.00%) 
PSEUDOMEMBRANOUS COLITIS † 1  3/236 (1.27%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
PSEUDOMONAL BACTERAEMIA † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  1/22 (4.55%) 
PSEUDOMONAL SEPSIS † 1  3/236 (1.27%)  0/40 (0.00%)  2/153 (1.31%)  0/42 (0.00%)  0/22 (0.00%) 
RESPIRATORY TRACT INFECTION † 1  0/236 (0.00%)  2/40 (5.00%)  2/153 (1.31%)  0/42 (0.00%)  0/22 (0.00%) 
SEPSIS † 1  12/236 (5.08%)  1/40 (2.50%)  9/153 (5.88%)  2/42 (4.76%)  0/22 (0.00%) 
SEPTIC SHOCK † 1  4/236 (1.69%)  1/40 (2.50%)  4/153 (2.61%)  4/42 (9.52%)  0/22 (0.00%) 
SINUSITIS † 1  3/236 (1.27%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  1/22 (4.55%) 
SINUSITIS FUNGAL † 1  0/236 (0.00%)  0/40 (0.00%)  0/153 (0.00%)  1/42 (2.38%)  0/22 (0.00%) 
SOFT TISSUE INFECTION † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
STAPHYLOCOCCAL BACTERAEMIA † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  1/42 (2.38%)  0/22 (0.00%) 
STAPHYLOCOCCAL SEPSIS † 1  0/236 (0.00%)  0/40 (0.00%)  0/153 (0.00%)  1/42 (2.38%)  0/22 (0.00%) 
SYSTEMIC CANDIDA † 1  0/236 (0.00%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  1/22 (4.55%) 
TONSILLITIS † 1  0/236 (0.00%)  0/40 (0.00%)  2/153 (1.31%)  0/42 (0.00%)  0/22 (0.00%) 
TOOTH INFECTION † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
UPPER RESPIRATORY TRACT INFECTION † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
URINARY TRACT INFECTION † 1  7/236 (2.97%)  1/40 (2.50%)  3/153 (1.96%)  0/42 (0.00%)  0/22 (0.00%) 
UROSEPSIS † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
VAGINITIS GARDNERELLA † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
VULVAL ABSCESS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
ZYGOMYCOSIS † 1  0/236 (0.00%)  0/40 (0.00%)  0/153 (0.00%)  1/42 (2.38%)  0/22 (0.00%) 
Injury, poisoning and procedural complications           
ALLERGIC TRANSFUSION REACTION † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
ANKLE FRACTURE † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
CONCUSSION † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
CRANIOCEREBRAL INJURY † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
FALL † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
FEMUR FRACTURE † 1  1/236 (0.42%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
HIP FRACTURE † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
LIGAMENT SPRAIN † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
RIB FRACTURE † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
ROAD TRAFFIC ACCIDENT † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
SUBDURAL HAEMATOMA † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
TENDON RUPTURE † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
TRANSFUSION REACTION † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
Investigations           
TROPONIN INCREASED † 1  0/236 (0.00%)  0/40 (0.00%)  0/153 (0.00%)  1/42 (2.38%)  0/22 (0.00%) 
URINE OUTPUT DECREASED † 1  0/236 (0.00%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
WEIGHT DECREASED † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
Metabolism and nutrition disorders           
CACHEXIA † 1  1/236 (0.42%)  0/40 (0.00%)  2/153 (1.31%)  0/42 (0.00%)  0/22 (0.00%) 
DECREASED APPETITE † 1  0/236 (0.00%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  1/22 (4.55%) 
DEHYDRATION † 1  3/236 (1.27%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
FAILURE TO THRIVE † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
FLUID OVERLOAD † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
HYPERGLYCAEMIA † 1  0/236 (0.00%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
HYPOKALAEMIA † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
HYPONATRAEMIA † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
TUMOUR LYSIS SYNDROME † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
Musculoskeletal and connective tissue disorders           
ARTHRALGIA † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
ARTHRITIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
BACK PAIN † 1  3/236 (1.27%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
BONE PAIN † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
HAEMARTHROSIS † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
MUSCULAR WEAKNESS † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
MYALGIA † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
OSTEOARTHRITIS † 1  0/236 (0.00%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  1/22 (4.55%) 
PAIN IN EXTREMITY † 1  0/236 (0.00%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
SPINAL OSTEOARTHRITIS † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
ACUTE MYELOID LEUKAEMIA † 1  26/236 (11.02%)  12/40 (30.00%)  17/153 (11.11%)  0/42 (0.00%)  1/22 (4.55%) 
CHLOROMA † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
LEUKAEMIC INFILTRATION BRAIN † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
OVARIAN CANCER METASTATIC † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
TUMOUR FLARE † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
Nervous system disorders           
CEREBRAL HAEMORRHAGE † 1  1/236 (0.42%)  2/40 (5.00%)  0/153 (0.00%)  1/42 (2.38%)  0/22 (0.00%) 
CEREBRAL INFARCTION † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  1/22 (4.55%) 
CEREBROVASCULAR ACCIDENT † 1  1/236 (0.42%)  0/40 (0.00%)  2/153 (1.31%)  0/42 (0.00%)  0/22 (0.00%) 
COGNITIVE DISORDER † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
CONVULSION † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
DIZZINESS † 1  5/236 (2.12%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  1/22 (4.55%) 
FEBRILE CONVULSION † 1  0/236 (0.00%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
HAEMORRHAGE INTRACRANIAL † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  1/42 (2.38%)  0/22 (0.00%) 
HEADACHE † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
LOSS OF CONSCIOUSNESS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
ORTHOSTATIC INTOLERANCE † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
PRESYNCOPE † 1  2/236 (0.85%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
SUBARACHNOID HAEMORRHAGE † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
SYNCOPE † 1  4/236 (1.69%)  0/40 (0.00%)  2/153 (1.31%)  1/42 (2.38%)  1/22 (4.55%) 
TRANSIENT ISCHAEMIC ATTACK † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
Psychiatric disorders           
CONFUSIONAL STATE † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
Renal and urinary disorders           
BLADDER MASS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
HAEMATURIA † 1  0/236 (0.00%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  1/22 (4.55%) 
RENAL COLIC † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
RENAL FAILURE † 1  3/236 (1.27%)  0/40 (0.00%)  2/153 (1.31%)  0/42 (0.00%)  0/22 (0.00%) 
RENAL FAILURE ACUTE † 1  3/236 (1.27%)  0/40 (0.00%)  2/153 (1.31%)  1/42 (2.38%)  0/22 (0.00%) 
RENAL FAILURE CHRONIC † 1  0/236 (0.00%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
RENAL IMPAIRMENT † 1  0/236 (0.00%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
RENAL TUBULAR NECROSIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
URINARY RETENTION † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
ACUTE PULMONARY OEDEMA † 1  1/236 (0.42%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
ACUTE RESPIRATORY DISTRESS SYNDROME † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  1/42 (2.38%)  0/22 (0.00%) 
ACUTE RESPIRATORY FAILURE † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  1/42 (2.38%)  0/22 (0.00%) 
ASTHMA † 1  0/236 (0.00%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
CHRONIC OBSTRUCTIVE PULMONARY DISEASE † 1  0/236 (0.00%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
DYSPNOEA † 1  5/236 (2.12%)  1/40 (2.50%)  3/153 (1.96%)  1/42 (2.38%)  0/22 (0.00%) 
EPISTAXIS † 1  2/236 (0.85%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
LUNG DISORDER † 1  1/236 (0.42%)  0/40 (0.00%)  2/153 (1.31%)  0/42 (0.00%)  0/22 (0.00%) 
ORGANISING PNEUMONIA † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
OROPHARYNGEAL PAIN † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
PLEURAL EFFUSION † 1  2/236 (0.85%)  0/40 (0.00%)  2/153 (1.31%)  1/42 (2.38%)  0/22 (0.00%) 
PNEUMONIA ASPIRATION † 1  0/236 (0.00%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
PNEUMONITIS † 1  1/236 (0.42%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
PRODUCTIVE COUGH † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
PULMONARY ALVEOLAR HAEMORRHAGE † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
PULMONARY EMBOLISM † 1  1/236 (0.42%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
PULMONARY HAEMORRHAGE † 1  0/236 (0.00%)  1/40 (2.50%)  1/153 (0.65%)  0/42 (0.00%)  0/22 (0.00%) 
PULMONARY OEDEMA † 1  2/236 (0.85%)  0/40 (0.00%)  2/153 (1.31%)  0/42 (0.00%)  0/22 (0.00%) 
RESPIRATORY FAILURE † 1  3/236 (1.27%)  1/40 (2.50%)  6/153 (3.92%)  2/42 (4.76%)  0/22 (0.00%) 
Skin and subcutaneous tissue disorders           
SKIN ULCER † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
Vascular disorders           
DEEP VEIN THROMBOSIS † 1  2/236 (0.85%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
HAEMATOMA † 1  2/236 (0.85%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
HYPERTENSION † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
HYPOTENSION † 1  4/236 (1.69%)  1/40 (2.50%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
PERIPHERAL ISCHAEMIA † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
PHLEBITIS † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
THROMBOPHLEBITIS SUPERFICIAL † 1  1/236 (0.42%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Azacitidine BSC Only Low-dose Cytarabine Intensive Chemotherapy Azacitidine-extension
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   226/236 (95.76%)   33/40 (82.50%)   151/153 (98.69%)   42/42 (100.00%)   18/22 (81.82%) 
Blood and lymphatic system disorders           
ANAEMIA † 1  41/236 (17.37%)  3/40 (7.50%)  32/153 (20.92%)  7/42 (16.67%)  4/22 (18.18%) 
FEBRILE NEUTROPENIA † 1  28/236 (11.86%)  2/40 (5.00%)  21/153 (13.73%)  12/42 (28.57%)  0/22 (0.00%) 
LEUKOCYTOSIS † 1  13/236 (5.51%)  2/40 (5.00%)  11/153 (7.19%)  0/42 (0.00%)  0/22 (0.00%) 
LEUKOPENIA † 1  22/236 (9.32%)  0/40 (0.00%)  15/153 (9.80%)  6/42 (14.29%)  1/22 (4.55%) 
NEUTROPENIA † 1  69/236 (29.24%)  1/40 (2.50%)  43/153 (28.10%)  14/42 (33.33%)  6/22 (27.27%) 
THROMBOCYTOPENIA † 1  60/236 (25.42%)  2/40 (5.00%)  37/153 (24.18%)  9/42 (21.43%)  6/22 (27.27%) 
Cardiac disorders           
ATRIAL FIBRILLATION † 1  12/236 (5.08%)  2/40 (5.00%)  9/153 (5.88%)  1/42 (2.38%)  1/22 (4.55%) 
TACHYCARDIA † 1  5/236 (2.12%)  3/40 (7.50%)  2/153 (1.31%)  2/42 (4.76%)  0/22 (0.00%) 
Gastrointestinal disorders           
ABDOMINAL DISTENSION † 1  3/236 (1.27%)  4/40 (10.00%)  4/153 (2.61%)  0/42 (0.00%)  0/22 (0.00%) 
ABDOMINAL PAIN † 1  30/236 (12.71%)  3/40 (7.50%)  16/153 (10.46%)  7/42 (16.67%)  1/22 (4.55%) 
ABDOMINAL PAIN UPPER † 1  19/236 (8.05%)  0/40 (0.00%)  6/153 (3.92%)  6/42 (14.29%)  0/22 (0.00%) 
CONSTIPATION † 1  99/236 (41.95%)  9/40 (22.50%)  42/153 (27.45%)  16/42 (38.10%)  1/22 (4.55%) 
DIARRHOEA † 1  87/236 (36.86%)  5/40 (12.50%)  34/153 (22.22%)  21/42 (50.00%)  5/22 (22.73%) 
DYSPEPSIA † 1  16/236 (6.78%)  2/40 (5.00%)  14/153 (9.15%)  6/42 (14.29%)  0/22 (0.00%) 
HAEMORRHOIDS † 1  14/236 (5.93%)  1/40 (2.50%)  7/153 (4.58%)  4/42 (9.52%)  3/22 (13.64%) 
MOUTH ULCERATION † 1  11/236 (4.66%)  1/40 (2.50%)  8/153 (5.23%)  1/42 (2.38%)  0/22 (0.00%) 
NAUSEA † 1  93/236 (39.41%)  3/40 (7.50%)  43/153 (28.10%)  24/42 (57.14%)  3/22 (13.64%) 
STOMATITIS † 1  20/236 (8.47%)  2/40 (5.00%)  14/153 (9.15%)  4/42 (9.52%)  2/22 (9.09%) 
VOMITING † 1  53/236 (22.46%)  3/40 (7.50%)  24/153 (15.69%)  8/42 (19.05%)  3/22 (13.64%) 
General disorders           
ASTHENIA † 1  53/236 (22.46%)  8/40 (20.00%)  32/153 (20.92%)  5/42 (11.90%)  6/22 (27.27%) 
CATHETER SITE PAIN † 1  3/236 (1.27%)  0/40 (0.00%)  1/153 (0.65%)  3/42 (7.14%)  0/22 (0.00%) 
CHILLS † 1  11/236 (4.66%)  1/40 (2.50%)  7/153 (4.58%)  4/42 (9.52%)  0/22 (0.00%) 
FATIGUE † 1  53/236 (22.46%)  10/40 (25.00%)  19/153 (12.42%)  4/42 (9.52%)  3/22 (13.64%) 
INJECTION SITE ERYTHEMA † 1  29/236 (12.29%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  1/22 (4.55%) 
INJECTION SITE PAIN † 1  12/236 (5.08%)  0/40 (0.00%)  1/153 (0.65%)  0/42 (0.00%)  1/22 (4.55%) 
INJECTION SITE REACTION † 1  30/236 (12.71%)  0/40 (0.00%)  0/153 (0.00%)  0/42 (0.00%)  0/22 (0.00%) 
MALAISE † 1  7/236 (2.97%)  2/40 (5.00%)  3/153 (1.96%)  0/42 (0.00%)  0/22 (0.00%) 
MUCOSAL INFLAMMATION † 1  8/236 (3.39%)  0/40 (0.00%)  14/153 (9.15%)  3/42 (7.14%)  0/22 (0.00%) 
OEDEMA † 1  8/236 (3.39%)  0/40 (0.00%)  3/153 (1.96%)  1/42 (2.38%)  2/22 (9.09%) 
OEDEMA PERIPHERAL † 1  55/236 (23.31%)  6/40 (15.00%)  33/153 (21.57%)  9/42 (21.43%)  2/22 (9.09%) 
PAIN † 1  16/236 (6.78%)  5/40 (12.50%)  5/153 (3.27%)  3/42 (7.14%)  2/22 (9.09%) 
PYREXIA † 1  77/236 (32.63%)  7/40 (17.50%)  56/153 (36.60%)  21/42 (50.00%)  4/22 (18.18%) 
Infections and infestations           
CELLULITIS † 1  13/236 (5.51%)  3/40 (7.50%)  7/153 (4.58%)  0/42 (0.00%)  0/22 (0.00%) 
LUNG INFECTION † 1  1/236 (0.42%)  0/40 (0.00%)  3/153 (1.96%)  3/42 (7.14%)  0/22 (0.00%) 
NASOPHARYNGITIS † 1  13/236 (5.51%)  2/40 (5.00%)  5/153 (3.27%)  0/42 (0.00%)  2/22 (9.09%) 
ORAL CANDIDIASIS † 1  16/236 (6.78%)  4/40 (10.00%)  4/153 (2.61%)  3/42 (7.14%)  0/22 (0.00%) 
ORAL HERPES † 1  15/236 (6.36%)  2/40 (5.00%)  8/153 (5.23%)  6/42 (14.29%)  0/22 (0.00%) 
PHARYNGITIS † 1  9/236 (3.81%)  1/40 (2.50%)  5/153 (3.27%)  1/42 (2.38%)  2/22 (9.09%) 
PNEUMONIA † 1  16/236 (6.78%)  0/40 (0.00%)  12/153 (7.84%)  4/42 (9.52%)  4/22 (18.18%) 
RESPIRATORY TRACT INFECTION † 1  5/236 (2.12%)  2/40 (5.00%)  4/153 (2.61%)  0/42 (0.00%)  0/22 (0.00%) 
SKIN INFECTION † 1  5/236 (2.12%)  0/40 (0.00%)  0/153 (0.00%)  1/42 (2.38%)  2/22 (9.09%) 
UPPER RESPIRATORY TRACT INFECTION † 1  18/236 (7.63%)  1/40 (2.50%)  5/153 (3.27%)  1/42 (2.38%)  1/22 (4.55%) 
URINARY TRACT INFECTION † 1  16/236 (6.78%)  3/40 (7.50%)  14/153 (9.15%)  0/42 (0.00%)  2/22 (9.09%) 
Injury, poisoning and procedural complications           
CONTUSION † 1  16/236 (6.78%)  3/40 (7.50%)  7/153 (4.58%)  2/42 (4.76%)  2/22 (9.09%) 
FALL † 1  14/236 (5.93%)  2/40 (5.00%)  7/153 (4.58%)  1/42 (2.38%)  1/22 (4.55%) 
LACERATION † 1  3/236 (1.27%)  0/40 (0.00%)  2/153 (1.31%)  0/42 (0.00%)  2/22 (9.09%) 
Investigations           
WEIGHT DECREASED † 1  30/236 (12.71%)  3/40 (7.50%)  2/153 (1.31%)  1/42 (2.38%)  1/22 (4.55%) 
Metabolism and nutrition disorders           
DECREASED APPETITE † 1  61/236 (25.85%)  8/40 (20.00%)  33/153 (21.57%)  7/42 (16.67%)  2/22 (9.09%) 
DEHYDRATION † 1  11/236 (4.66%)  2/40 (5.00%)  4/153 (2.61%)  1/42 (2.38%)  0/22 (0.00%) 
FLUID OVERLOAD † 1  8/236 (3.39%)  2/40 (5.00%)  0/153 (0.00%)  3/42 (7.14%)  0/22 (0.00%) 
FLUID RETENTION † 1  5/236 (2.12%)  0/40 (0.00%)  0/153 (0.00%)  3/42 (7.14%)  0/22 (0.00%) 
HYPOALBUMINAEMIA † 1  11/236 (4.66%)  1/40 (2.50%)  11/153 (7.19%)  7/42 (16.67%)  1/22 (4.55%) 
HYPOCALCAEMIA † 1  16/236 (6.78%)  0/40 (0.00%)  6/153 (3.92%)  3/42 (7.14%)  1/22 (4.55%) 
HYPOKALAEMIA † 1  54/236 (22.88%)  6/40 (15.00%)  45/153 (29.41%)  16/42 (38.10%)  3/22 (13.64%) 
HYPOMAGNESAEMIA † 1  21/236 (8.90%)  2/40 (5.00%)  9/153 (5.88%)  6/42 (14.29%)  1/22 (4.55%) 
HYPONATRAEMIA † 1  9/236 (3.81%)  0/40 (0.00%)  12/153 (7.84%)  3/42 (7.14%)  1/22 (4.55%) 
HYPOPHOSPHATAEMIA † 1  19/236 (8.05%)  2/40 (5.00%)  8/153 (5.23%)  6/42 (14.29%)  1/22 (4.55%) 
Musculoskeletal and connective tissue disorders           
ARTHRALGIA † 1  33/236 (13.98%)  2/40 (5.00%)  11/153 (7.19%)  3/42 (7.14%)  2/22 (9.09%) 
BACK PAIN † 1  36/236 (15.25%)  5/40 (12.50%)  22/153 (14.38%)  2/42 (4.76%)  1/22 (4.55%) 
BONE PAIN † 1  12/236 (5.08%)  2/40 (5.00%)  4/153 (2.61%)  0/42 (0.00%)  0/22 (0.00%) 
MUSCULOSKELETAL PAIN † 1  21/236 (8.90%)  2/40 (5.00%)  3/153 (1.96%)  1/42 (2.38%)  2/22 (9.09%) 
PAIN IN EXTREMITY † 1  26/236 (11.02%)  2/40 (5.00%)  11/153 (7.19%)  2/42 (4.76%)  2/22 (9.09%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
ACUTE MYELOID LEUKAEMIA † 1  27/236 (11.44%)  2/40 (5.00%)  21/153 (13.73%)  1/42 (2.38%)  0/22 (0.00%) 
Nervous system disorders           
DIZZINESS † 1  42/236 (17.80%)  3/40 (7.50%)  15/153 (9.80%)  4/42 (9.52%)  1/22 (4.55%) 
HEADACHE † 1  31/236 (13.14%)  1/40 (2.50%)  19/153 (12.42%)  6/42 (14.29%)  3/22 (13.64%) 
SCIATICA † 1  4/236 (1.69%)  2/40 (5.00%)  2/153 (1.31%)  0/42 (0.00%)  0/22 (0.00%) 
Psychiatric disorders           
AGITATION † 1  6/236 (2.54%)  3/40 (7.50%)  3/153 (1.96%)  0/42 (0.00%)  1/22 (4.55%) 
ANXIETY † 1  15/236 (6.36%)  4/40 (10.00%)  6/153 (3.92%)  2/42 (4.76%)  2/22 (9.09%) 
CONFUSIONAL STATE † 1  14/236 (5.93%)  3/40 (7.50%)  8/153 (5.23%)  3/42 (7.14%)  1/22 (4.55%) 
INSOMNIA † 1  36/236 (15.25%)  2/40 (5.00%)  11/153 (7.19%)  4/42 (9.52%)  1/22 (4.55%) 
Renal and urinary disorders           
HAEMATURIA † 1  5/236 (2.12%)  3/40 (7.50%)  8/153 (5.23%)  1/42 (2.38%)  0/22 (0.00%) 
RENAL FAILURE † 1  7/236 (2.97%)  2/40 (5.00%)  3/153 (1.96%)  3/42 (7.14%)  0/22 (0.00%) 
RENAL FAILURE ACUTE † 1  4/236 (1.69%)  2/40 (5.00%)  3/153 (1.96%)  1/42 (2.38%)  0/22 (0.00%) 
URINARY INCONTINENCE † 1  5/236 (2.12%)  2/40 (5.00%)  1/153 (0.65%)  2/42 (4.76%)  1/22 (4.55%) 
Respiratory, thoracic and mediastinal disorders           
COUGH † 1  54/236 (22.88%)  6/40 (15.00%)  36/153 (23.53%)  6/42 (14.29%)  5/22 (22.73%) 
DYSPNOEA † 1  41/236 (17.37%)  6/40 (15.00%)  35/153 (22.88%)  4/42 (9.52%)  1/22 (4.55%) 
DYSPNOEA EXERTIONAL † 1  10/236 (4.24%)  2/40 (5.00%)  6/153 (3.92%)  0/42 (0.00%)  0/22 (0.00%) 
EPISTAXIS † 1  29/236 (12.29%)  5/40 (12.50%)  21/153 (13.73%)  2/42 (4.76%)  4/22 (18.18%) 
HAEMOPTYSIS † 1  9/236 (3.81%)  2/40 (5.00%)  4/153 (2.61%)  2/42 (4.76%)  0/22 (0.00%) 
HICCUPS † 1  0/236 (0.00%)  1/40 (2.50%)  0/153 (0.00%)  3/42 (7.14%)  1/22 (4.55%) 
OROPHARYNGEAL PAIN † 1  16/236 (6.78%)  2/40 (5.00%)  11/153 (7.19%)  4/42 (9.52%)  1/22 (4.55%) 
PLEURAL EFFUSION † 1  12/236 (5.08%)  1/40 (2.50%)  2/153 (1.31%)  1/42 (2.38%)  2/22 (9.09%) 
PRODUCTIVE COUGH † 1  9/236 (3.81%)  0/40 (0.00%)  10/153 (6.54%)  3/42 (7.14%)  1/22 (4.55%) 
Skin and subcutaneous tissue disorders           
ERYTHEMA † 1  18/236 (7.63%)  0/40 (0.00%)  6/153 (3.92%)  3/42 (7.14%)  0/22 (0.00%) 
PETECHIAE † 1  12/236 (5.08%)  0/40 (0.00%)  16/153 (10.46%)  1/42 (2.38%)  0/22 (0.00%) 
PRURITUS † 1  25/236 (10.59%)  1/40 (2.50%)  10/153 (6.54%)  6/42 (14.29%)  0/22 (0.00%) 
RASH † 1  26/236 (11.02%)  0/40 (0.00%)  14/153 (9.15%)  8/42 (19.05%)  1/22 (4.55%) 
SKIN LESION † 1  4/236 (1.69%)  2/40 (5.00%)  5/153 (3.27%)  0/42 (0.00%)  1/22 (4.55%) 
SKIN ULCER † 1  7/236 (2.97%)  2/40 (5.00%)  2/153 (1.31%)  1/42 (2.38%)  0/22 (0.00%) 
Vascular disorders           
HAEMATOMA † 1  16/236 (6.78%)  2/40 (5.00%)  7/153 (4.58%)  1/42 (2.38%)  2/22 (9.09%) 
HYPERTENSION † 1  16/236 (6.78%)  1/40 (2.50%)  13/153 (8.50%)  4/42 (9.52%)  2/22 (9.09%) 
HYPOTENSION † 1  19/236 (8.05%)  3/40 (7.50%)  14/153 (9.15%)  1/42 (2.38%)  1/22 (4.55%) 
PHLEBITIS † 1  7/236 (2.97%)  2/40 (5.00%)  4/153 (2.61%)  2/42 (4.76%)  1/22 (4.55%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
[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.
The investigator shall have the right to publish and/or present study data provided that the investigator shall (i) furnish the sponsor a copy of any proposed publication or presentation 60 days in advance of the submission and (ii) delete any confidential information of the sponsor and (iii) delay submission for up to 90 days to permit the preparation and filing of intellectual property applications or until sponsor gives its consent in a timely manner.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Anne McClain, Senior Manager Clinical Trial Disclosure
Organization: Celgene
Phone: 888-260-1599
EMail: ClinicalTrialDisclosure@celgene.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT01074047    
Other Study ID Numbers: AZA-AML-001
First Submitted: February 16, 2010
First Posted: February 24, 2010
Results First Submitted: January 22, 2015
Results First Posted: February 26, 2015
Last Update Posted: August 29, 2017