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Acalabrutinib, Obinutuzumab and Chlorambucil in Treatment naïve CLL (ElevateTN)

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ClinicalTrials.gov Identifier: NCT02475681
Recruitment Status : Active, not recruiting
First Posted : June 19, 2015
Results First Posted : January 10, 2023
Last Update Posted : March 4, 2024
Sponsor:
Information provided by (Responsible Party):
Acerta Pharma BV

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Condition Chronic Lymphocytic Leukemia
Interventions Drug: Acalabrutinib
Drug: Obinutuzumab
Drug: Chlorambucil
Enrollment 535
Recruitment Details A randomized, multicenter, open-label, 3 arm phase 3 study of Obinutuzumab in combination with Chlorambucil (Chlb+Obin), Acalabrutinib in combination with Obinutuzumab (Acala+Obin), and Acalabrutinib monotherapy (Acala) in subjects with previously untreated chronic lymphocytic leukemia. A total of 535 subjects recruited from 142 sites in 18 countries were randomized (1:1:1) as follows: 179/179 /177 subjects in Acla+Obin arm / Acala arm / Chlb+Obin arm respectively.
Pre-assignment Details  
Arm/Group Title Arm A: Obinutuzumab in Combination With Chlorambucil Arm B: Acalabrutinib in Combination With Obinutuzumab Arm C: Acalabrutinib Monotherapy
Hide Arm/Group Description Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles, starting from cycle1 to cycle 6. Chlorambucil will be orally administered on Days 1 and 15 of Cycles 1 through 6. At investigator discretion, subjects randomized to this treatment arm, who had IRC-confirmed disease progression, were eligible to receive crossover treatment with single-agent acalabrutinib at 100 mg BID until disease progression or unacceptable toxicity. Acalabrutinib (ACP-196) will be orally administered starting on Cycle 1 Day 1. Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles, starting in Cycle 2 Day 1. Daily administration of Acalabrutinib (ACP-196) will continue until disease progression or unacceptable toxicity. Acalabrutinib (ACP-196) will be orally administered on Cycle 1 Day 1 until disease progression or unacceptable toxicity. Acalabrutinib
Period Title: Overall Study
Started [1] 177 179 179
Crossed Over From Arm A to Arm C 45 0 0
Completed 145 0 0
Not Completed 32 179 179
Reason Not Completed
Death             16             6             9
Physician Decision             0             3             1
Withdrawal by Subject             12             6             9
Lost to Follow-up             2             1             3
Ongoing in Study             0             163             157
Reasons other than above listed             2             0             0
[1]
Randomized
Arm/Group Title Obinutuzumab in Combination With Chlorambucil Acalabrutinib in Combination With Obinutuzumab Acalabrutinib Monotherapy Total
Hide Arm/Group Description Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles starting at Cycle 1 Day 1. Chlorambucil will be orally administered on Days 1 and 15 of Cycles 1 through 6. Obinutuzumab Chlorambucil Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles starting at Cycle 2 Day 1. Acalabrutinib (ACP-196) will be orally administered starting on Cycle 1 Day 1. Daily administration of Acalabrutinib (ACP-196) will continue until disease progression or unacceptable toxicity. Acalabrutinib Obinutuzumab Acalabrutinib will be orally administered on Cycle 1 Day 1 until disease progression or unacceptable toxicity. Acalabrutinib Total of all reporting groups
Overall Number of Baseline Participants 177 179 179 535
Hide Baseline Analysis Population Description
Analysis was performed on intent-to-treat (ITT) population, which included all randomized participants grouped according to assigned treatment.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 177 participants 179 participants 179 participants 535 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
24
  13.6%
35
  19.6%
28
  15.6%
87
  16.3%
>=65 years
153
  86.4%
144
  80.4%
151
  84.4%
448
  83.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 177 participants 179 participants 179 participants 535 participants
Female
71
  40.1%
68
  38.0%
68
  38.0%
207
  38.7%
Male
106
  59.9%
111
  62.0%
111
  62.0%
328
  61.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 177 participants 179 participants 179 participants 535 participants
Hispanic or Latino
11
   6.2%
2
   1.1%
11
   6.1%
24
   4.5%
Not Hispanic or Latino
156
  88.1%
169
  94.4%
156
  87.2%
481
  89.9%
Unknown or Not Reported
10
   5.6%
8
   4.5%
12
   6.7%
30
   5.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 177 participants 179 participants 179 participants 535 participants
American Indian or Alaska Native
1
   0.6%
0
   0.0%
0
   0.0%
1
   0.2%
Asian
0
   0.0%
3
   1.7%
0
   0.0%
3
   0.6%
Native Hawaiian or Other Pacific Islander
1
   0.6%
0
   0.0%
0
   0.0%
1
   0.2%
Black or African American
4
   2.3%
5
   2.8%
4
   2.2%
13
   2.4%
White
165
  93.2%
164
  91.6%
170
  95.0%
499
  93.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
6
   3.4%
7
   3.9%
5
   2.8%
18
   3.4%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 177 participants 179 participants 179 participants 535 participants
Belgium
5
   2.8%
5
   2.8%
3
   1.7%
13
   2.4%
France
3
   1.7%
3
   1.7%
1
   0.6%
7
   1.3%
Germany
3
   1.7%
1
   0.6%
3
   1.7%
7
   1.3%
Italy
11
   6.2%
9
   5.0%
5
   2.8%
25
   4.7%
Spain
7
   4.0%
3
   1.7%
3
   1.7%
13
   2.4%
Sweden
1
   0.6%
3
   1.7%
3
   1.7%
7
   1.3%
United Kingdom
12
   6.8%
16
   8.9%
17
   9.5%
45
   8.4%
Brazil
4
   2.3%
5
   2.8%
5
   2.8%
14
   2.6%
Chile
2
   1.1%
0
   0.0%
3
   1.7%
5
   0.9%
Colombia
1
   0.6%
0
   0.0%
0
   0.0%
1
   0.2%
Canada
7
   4.0%
8
   4.5%
7
   3.9%
22
   4.1%
United States
54
  30.5%
56
  31.3%
63
  35.2%
173
  32.3%
Hungary
17
   9.6%
26
  14.5%
15
   8.4%
58
  10.8%
Lithuania
9
   5.1%
2
   1.1%
6
   3.4%
17
   3.2%
Poland
14
   7.9%
20
  11.2%
25
  14.0%
59
  11.0%
Australia
9
   5.1%
9
   5.0%
8
   4.5%
26
   4.9%
New Zealand
8
   4.5%
4
   2.2%
5
   2.8%
17
   3.2%
Israel
10
   5.6%
9
   5.0%
7
   3.9%
26
   4.9%
IXRS Randomization Stratification Factor: Presence of 17p Deletion  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 177 participants 179 participants 179 participants 535 participants
Yes
17
   9.6%
21
  11.7%
19
  10.6%
57
  10.7%
No
160
  90.4%
158
  88.3%
160
  89.4%
478
  89.3%
IXRS Randomization Stratification Factor: ECOG Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 177 participants 179 participants 179 participants 535 participants
0-1 (0=Fully Active; 1 =Restricted in Physically Strenuous Activity)
168
  94.9%
169
  94.4%
167
  93.3%
504
  94.2%
2 (2=Ambulatory and capable of all selfcare but unable to carry out any work activities)
9
   5.1%
10
   5.6%
12
   6.7%
31
   5.8%
[1]
Measure Description: Lower Grade is Better. 0=Fully active; 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2=Ambulatory and capable of all selfcare but unable to carry out any work activities;
IXRS Randomization Stratification Factor: Geographic Region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 177 participants 179 participants 179 participants 535 participants
North America and West Europe
103
  58.2%
104
  58.1%
105
  58.7%
312
  58.3%
Other
74
  41.8%
75
  41.9%
74
  41.3%
223
  41.7%
1.Primary Outcome
Title Progression-free Survival by IRC (Independent Review Committee) Assessment in Arm A Compared to Arm B
Hide Description To evaluate the efficacy of obinutuzumab in combination with chlorambucil (Arm A) compared with acalabrutinib in combination with obinutuzumab (Arm B) based on IRC assessment of progression-free survival (PFS) per International Workshop on Chronic Lymphocytic Leukemia criteria (IWCLL; Hallek et al. 2008) with incorporation of the clarification for treatment-related lymphocytosis (Cheson et al. 2012), hereafter referred to as IWCLL 2008 criteria, in subjects with previously untreated CLL. PFS, defined as the time from date of randomization to the date of first IRC-assessed disease progression or death due to any cause, whichever comes first.
Time Frame IRC assessments were done from randomization date until disease progression or death or IRC discontinuation date on 08Feb2019 (as the IA based on this data cutoff date showed the study crossing superiority boundary) whichever comes first up to 40 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT)
Arm/Group Title Arm A: Obinutuzumab in Combination With Chlorambucil Arm B: Acalabrutinib in Combination With Obinutuzumab
Hide Arm/Group Description:
Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles, starting from cycle1 to cycle 6. Chlorambucil will be orally administered on Days 1 and 15 of Cycles 1 through 6. At investigator discretion, subjects randomized to this treatment arm, who had IRC-confirmed disease progression, were eligible to receive crossover treatment with single-agent acalabrutinib at 100 mg BID until disease progression or unacceptable toxicity.
Acalabrutinib (ACP-196) will be orally administered starting on Cycle 1 Day 1. Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles, starting in Cycle 2 Day 1. Daily administration of Acalabrutinib (ACP-196) will continue until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 177 179
Median (95% Confidence Interval)
Unit of Measure: Months
22.6
(20.2 to 27.8)
NA [1] 
(NA to NA)
[1]

Median and 95% CIs for Arm B = NA (not reached) since insufficient numbers of subjects with events (Range = 0.0+ to 39.4+ months).

"+" indicates a value from a censored subject.

Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Obinutuzumab in Combination With Chlorambucil, Arm B: Acalabrutinib in Combination With Obinutuzumab
Comments The primary test to compare PFS between treatment arms was the two-sided log-rank test, stratified by randomization stratification factors. The estimate of the HR (Arm B/Arm A) and the corresponding 95% CI was computed using a Cox proportional hazards model stratified by randomization stratification factors. Randomization stratification factors were based on the data recorded in IXRS.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments Stratified by randomization stratification factors as recorded in IXRS
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
0.06 to 0.17
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Progression-free Survival by IRC Assessment Arm A Versus Arm C
Hide Description To evaluate the efficacy of obinutuzumab in combination with chlorambucil (Arm A) compared with acalabrutinib monotherapy (Arm C) based on IRC assessment of progression-free survival (PFS) per International Workshop on Chronic Lymphocytic Leukemia criteria (IWCLL; Hallek et al. 2008) with incorporation of the clarification for treatment-related lymphocytosis (Cheson et al. 2012), hereafter referred to as IWCLL 2008 criteria, in subjects with previously untreated CLL. PFS, defined as the time from date of randomization to the date of first IRC-assessed disease progression or death due to any cause, whichever comes first.
Time Frame IRC assessments were done from randomization date until disease progression or death or IRC discontinuation date on 08Feb2019 (as the IA based on this data cutoff date showed the study crossing superiority boundary) whichever comes first up to 40 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT)
Arm/Group Title Arm A: Obinutuzumab in Combination With Chlorambucil Arm C: Acalabrutinib Monotherapy
Hide Arm/Group Description:
Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles, starting from cycle1 to cycle 6. Chlorambucil will be orally administered on Days 1 and 15 of Cycles 1 through 6. At investigator discretion, subjects randomized to this treatment arm, who had IRC-confirmed disease progression, were eligible to receive crossover treatment with single-agent acalabrutinib at 100 mg BID until disease progression or unacceptable toxicity.
Acalabrutinib (ACP-196) will be orally administered on Cycle 1 Day 1 until disease progression or unacceptable toxicity. Acalabrutinib
Overall Number of Participants Analyzed 177 179
Median (95% Confidence Interval)
Unit of Measure: Months
22.6
(20.2 to 27.6)
NA [1] 
(34.2 to NA)
[1]
The median PFS for Arm C was not reached (Range = 0.0+ to 39.5+ months). "+" indicates a value from a censored subject.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Obinutuzumab in Combination With Chlorambucil, Arm C: Acalabrutinib Monotherapy
Comments The test to compare PFS between treatment Arms A and C was the two-sided log-rank test, stratified by randomization stratification factors. The estimate of the HR and the corresponding 95% CI was computed using a Cox proportional hazards model stratified by randomization stratification factors. Randomization stratification factors were based on the data recorded in IXRS.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments Stratified by randomization stratification factors as recorded in IXRS
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
0.13 to 0.30
Estimation Comments [Not Specified]
3.Secondary Outcome
Title IRC-assessed Objective Response Rate (ORR) in Arm A Versus Arm B and Arm A Versus Arm C
Hide Description ORR was defined as the proportion of subjects who achieved a best response of CR, CRi, nPR, or PR at or before initiation of subsequent anticancer therapy. ORR including PRL was defined as the proportion of subjects who achieved a best response of CR, CRi, nPR, PR or PRL at or before initiation of subsequent anticancer therapy
Time Frame IRC assessments were done from randomization date until disease progression or death or IRC discontinuation date on 08Feb2019 (as the IA based on this data cutoff date showed the study crossing superiority boundary) whichever comes first up to 40 months.
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat
Arm/Group Title Arm A: Obinutuzumab in Combination With Chlorambucil Arm B: Acalabrutinib in Combination With Obinutuzumab Arm C: Acalabrutinib Monotherapy
Hide Arm/Group Description:
Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles, starting from cycle1 to cycle 6. Chlorambucil will be orally administered on Days 1 and 15 of Cycles 1 through 6. At investigator discretion, subjects randomized to this treatment arm, who had IRC-confirmed disease progression, were eligible to receive crossover treatment with single-agent acalabrutinib at 100 mg BID until disease progression or unacceptable toxicity.
Acalabrutinib (ACP-196) will be orally administered starting on Cycle 1 Day 1. Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles, starting in Cycle 2 Day 1. Daily administration of Acalabrutinib (ACP-196) will continue until disease progression or unacceptable toxicity.
Acalabrutinib (ACP-196) will be orally administered on Cycle 1 Day 1 until disease progression or unacceptable toxicity. Acalabrutinib
Overall Number of Participants Analyzed 177 179 179
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
78.5
(71.9 to 83.9)
93.9
(89.3 to 96.5)
85.5
(79.6 to 89.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Obinutuzumab in Combination With Chlorambucil, Arm B: Acalabrutinib in Combination With Obinutuzumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenzel test with adjustment for randomization stratification factors as recorded in IXRS
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 15.3
Confidence Interval (2-Sided) 95%
8.3 to 22.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: Obinutuzumab in Combination With Chlorambucil, Arm C: Acalabrutinib Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0763
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenzel test with adjustment for randomization stratification factors as recorded in IXRS.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 6.9
Confidence Interval (2-Sided) 95%
-1.0 to 14.9
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time to Next Treatment (TTNT) in Arm A Versus Arm B and Arm A Versus Arm C
Hide Description TTNT was defined as the time from randomization to start date of non-protocol specified subsequent anticancer therapy for CLL or death due to any cause, whichever came first. TTNT was analyzed in the same fashion as that for the primary efficacy analysis
Time Frame From randomization date to start of non-protocol specified subsequent anticancer therapy for CLL or death due to any cause, whichever came first assessed up to 40 months of follow-up.
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT)
Arm/Group Title Arm A: Obinutuzumab in Combination With Chlorambucil Arm B: Acalabrutinib in Combination With Obinutuzumab Arm C: Acalabrutinib Monotherapy
Hide Arm/Group Description:
Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles, starting from cycle1 to cycle 6. Chlorambucil will be orally administered on Days 1 and 15 of Cycles 1 through 6. At investigator discretion, subjects randomized to this treatment arm, who had IRC-confirmed disease progression, were eligible to receive crossover treatment with single-agent acalabrutinib at 100 mg BID until disease progression or unacceptable toxicity.
Acalabrutinib (ACP-196) will be orally administered starting on Cycle 1 Day 1. Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles, starting in Cycle 2 Day 1. Daily administration of Acalabrutinib (ACP-196) will continue until disease progression or unacceptable toxicity.
Acalabrutinib (ACP-196) will be orally administered on Cycle 1 Day 1 until disease progression or unacceptable toxicity. Acalabrutinib
Overall Number of Participants Analyzed 177 179 179
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(28.9 to NA)
NA [2] 
(NA to NA)
NA [3] 
(NA to NA)
[1]

The median TTNT was not reached for obinutuzumab+chlorambucil (range: 0.0+ to 39.6+ months).

"+" indicates a value from a censored subject.

[2]

The median TTNT was not reached for acalabrutinib+obinutuzumab (range: 1.3-40.3+ months).

"+" indicates a value from a censored subject.

[3]

The median TTNT was not reached for acalabrutinib monotherapy (range: 0.1+ to 40.1+ months).

"+" indicates a value from a censored subject.

Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Obinutuzumab in Combination With Chlorambucil, Arm B: Acalabrutinib in Combination With Obinutuzumab
Comments The test to compare TTNT between treatment Arms A versus B and Arms A versus C was the two-sided log-rank test, stratified by randomization stratification factors. The estimate of the HR and the corresponding 95% CI was computed using a Cox proportional hazards model stratified by randomization stratification factors. Randomization stratification factors were based on the data recorded in IXRS.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments Stratified by randomization stratification factors as recorded in IXRS
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
0.08 to 0.26
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: Obinutuzumab in Combination With Chlorambucil, Arm C: Acalabrutinib Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value based on stratified by randomization stratification factors as recorded in IXRS
Method Log Rank
Comments Stratified by randomization stratification factors as recorded in IXRS
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
0.15 to 0.40
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Overall Survival (OS) in Arm A Versus Arm B and Arm A Versus Arm C
Hide Description OS was defined as the time from the date of randomization to death due to any cause.
Time Frame From randomization date until death, withdrawal by subject, lost to follow-up, or by analysis data cut off date on 08Feb2019 whichever comes first up to 40 months of follow-up.
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT)
Arm/Group Title Arm A: Obinutuzumab in Combination With Chlorambucil Arm B: Acalabrutinib in Combination With Obinutuzumab Arm C: Acalabrutinib Monotherapy
Hide Arm/Group Description:
Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles, starting from cycle1 to cycle 6. Chlorambucil will be orally administered on Days 1 and 15 of Cycles 1 through 6. At investigator discretion, subjects randomized to this treatment arm, who had IRC-confirmed disease progression, were eligible to receive crossover treatment with single-agent acalabrutinib at 100 mg BID until disease progression or unacceptable toxicity.
Acalabrutinib (ACP-196) will be orally administered starting on Cycle 1 Day 1. Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles, starting in Cycle 2 Day 1. Daily administration of Acalabrutinib (ACP-196) will continue until disease progression or unacceptable toxicity.
Acalabrutinib (ACP-196) will be orally administered on Cycle 1 Day 1 until disease progression or unacceptable toxicity. Acalabrutinib
Overall Number of Participants Analyzed 177 179 179
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [2] 
(NA to NA)
NA [3] 
(NA to NA)
[1]

The median and corresponding 95% CI for the OS in Arm A was not reached due to insufficient subjects with events (Range of OS =1.7 to 40.4+ months).

"+" indicates a value from a censored subject.

[2]

The median and corresponding 95% CI for the OS in Arm B was not reached due to insufficient subjects with events (Range of OS =0.1+ to 40.8+ months).

"+" indicates a value from a censored subject.

[3]
The median and corresponding 95% CI for the OS in Arm C was not reached due to insufficient subjects with events. (Range of OS = 0.0+ to 40.7+ months) "+" indicates a value from a censored subject.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Obinutuzumab in Combination With Chlorambucil, Arm B: Acalabrutinib in Combination With Obinutuzumab
Comments The test to compare overall survival between treatment Arms A versus B and Arms A versus C was the two-sided log-rank test, stratified by randomization stratification factors. The estimate of the HR and the corresponding 95% CI was computed using a Cox proportional hazards model stratified by randomization stratification factors. Randomization stratification factors were based on the data recorded in IXRS.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0577
Comments [Not Specified]
Method Log Rank
Comments Stratified by randomization stratification factors as recorded in IXRS
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.21 to 1.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A: Obinutuzumab in Combination With Chlorambucil, Arm C: Acalabrutinib Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1556
Comments [Not Specified]
Method Log Rank
Comments Stratified by randomization stratification factors as recorded in IXRS
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.28 to 1.27
Estimation Comments [Not Specified]
Time Frame All adverse events were reported from randomization date until 30 days after the last dose of study drug or the start of new anticancer therapy (whichever comes first) up to 61 months. After this period, investigators reported SAEs or other AEs of concern that are believed to be related to prior treatment with study drug up to 5 years.
Adverse Event Reporting Description Data presented under All-Cause Mortality table are based on ITT Population (all randomized) as those presented in Participant Flow. Data presented under SAE and AE Tables are based on Safety Population (Subjects received at least one dose of study drug).
 
Arm/Group Title Arm A: Obinutuzumab in Combination With Chlorambucil Arm B: Acalabrutinib in Combination With Obinutuzumab Arm C: Acalabrutinib Monotherapy Arm A Cross-over: Obinutuzumab+Chlorambucil Crossover to Acalabrutinib Monotherapy
Hide Arm/Group Description Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles, starting from cycle1 to cycle 6. Chlorambucil will be orally administered on Days 1 and 15 of Cycles 1 through 6. At investigator discretion, subjects randomized to this treatment arm, who had IRC-confirmed disease progression, were eligible to receive crossover treatment with single-agent acalabrutinib at 100 mg BID until disease progression or unacceptable toxicity. Acalabrutinib (ACP-196) will be orally administered starting on Cycle 1 Day 1. Obinutuzumab IV infusions will be administered over a total of 6 treatment cycles, starting in Cycle 2 Day 1. Daily administration of Acalabrutinib (ACP-196) will continue until disease progression or unacceptable toxicity. Acalabrutinib will be orally administered on Cycle 1 Day 1 until disease progression or unacceptable toxicity. Acalabrutinib Obinutuzumab + Chlorambucil Crossover to Acalabrutinib 100 mg twice daily monotherapy
All-Cause Mortality
Arm A: Obinutuzumab in Combination With Chlorambucil Arm B: Acalabrutinib in Combination With Obinutuzumab Arm C: Acalabrutinib Monotherapy Arm A Cross-over: Obinutuzumab+Chlorambucil Crossover to Acalabrutinib Monotherapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   17/177 (9.60%)   9/179 (5.03%)   11/179 (6.15%)   2/45 (4.44%) 
Hide Serious Adverse Events
Arm A: Obinutuzumab in Combination With Chlorambucil Arm B: Acalabrutinib in Combination With Obinutuzumab Arm C: Acalabrutinib Monotherapy Arm A Cross-over: Obinutuzumab+Chlorambucil Crossover to Acalabrutinib Monotherapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   37/169 (21.89%)   69/178 (38.76%)   57/179 (31.84%)   6/45 (13.33%) 
Blood and lymphatic system disorders         
Anaemia †  0/169 (0.00%)  3/178 (1.69%)  4/179 (2.23%)  0/45 (0.00%) 
Febrile neutropenia †  7/169 (4.14%)  3/178 (1.69%)  2/179 (1.12%)  1/45 (2.22%) 
Autoimmune haemolytic anaemia †  0/169 (0.00%)  0/178 (0.00%)  2/179 (1.12%)  0/45 (0.00%) 
Haemolysis †  1/169 (0.59%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Iron deficiency anaemia †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Neutropenia †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Thrombocytopenia †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Cardiac disorders         
Acute coronary syndrome †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Acute myocardial infarction †  1/169 (0.59%)  1/178 (0.56%)  3/179 (1.68%)  1/45 (2.22%) 
Angina unstable †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Atrial fibrillation †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Atrial flutter †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Atrioventricular block complete †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Hypertensive heart disease †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Myocardial infarction †  0/169 (0.00%)  1/178 (0.56%)  1/179 (0.56%)  0/45 (0.00%) 
Myocardial ischaemia †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Pericardial effusion †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Pericarditis †  1/169 (0.59%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Aortic valve disease †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Bradycardia †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Cardiac arrest †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Cardiac failure †  0/169 (0.00%)  0/178 (0.00%)  2/179 (1.12%)  0/45 (0.00%) 
Cardiac failure congestive †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Cardiac tamponade †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Palpitations †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Pericarditis constrictive †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Endocrine disorders         
Goitre †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Eye disorders         
Macular oedema †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Retinal haemorrhage †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Gastrointestinal disorders         
Abdominal pain lower †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Ascites †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Diarrhoea †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Diverticulum †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Duodenal ulcer †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Gastric volvulus †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Gastrointestinal haemorrhage †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Haematemesis †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Hiatus hernia †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Obstructive pancreatitis †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Pancreatitis †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Abdominal pain †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Intestinal perforation †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Large intestine polyp †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Odynophagia †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Nausea †  0/169 (0.00%)  0/178 (0.00%)  0/179 (0.00%)  1/45 (2.22%) 
General disorders         
Asthenia †  2/169 (1.18%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Non-cardiac chest pain †  0/169 (0.00%)  1/178 (0.56%)  1/179 (0.56%)  0/45 (0.00%) 
Pyrexia †  2/169 (1.18%)  1/178 (0.56%)  1/179 (0.56%)  0/45 (0.00%) 
Chest pain †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Swelling †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Hepatobiliary disorders         
Cholangitis acute †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Cholecystitis acute †  0/169 (0.00%)  1/178 (0.56%)  1/179 (0.56%)  0/45 (0.00%) 
Cholelithiasis †  0/169 (0.00%)  1/178 (0.56%)  1/179 (0.56%)  0/45 (0.00%) 
Hepatitis toxic †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Biliary colic †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Immune system disorders         
Anaphylactic reaction †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Haemophagocytic lymphohistiocytosis †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Infections and infestations         
Pneumonia †  3/169 (1.78%)  12/178 (6.74%)  5/179 (2.79%)  0/45 (0.00%) 
Urosepsis †  0/169 (0.00%)  3/178 (1.69%)  0/179 (0.00%)  0/45 (0.00%) 
Cellulitis †  0/169 (0.00%)  2/178 (1.12%)  2/179 (1.12%)  0/45 (0.00%) 
Herpes zoster †  0/169 (0.00%)  2/178 (1.12%)  0/179 (0.00%)  0/45 (0.00%) 
Lower respiratory tract infection †  0/169 (0.00%)  2/178 (1.12%)  0/179 (0.00%)  0/45 (0.00%) 
Rhinovirus infection †  0/169 (0.00%)  2/178 (1.12%)  0/179 (0.00%)  0/45 (0.00%) 
Sepsis †  2/169 (1.18%)  2/178 (1.12%)  0/179 (0.00%)  0/45 (0.00%) 
Urinary tract infection †  0/169 (0.00%)  2/178 (1.12%)  3/179 (1.68%)  0/45 (0.00%) 
Bacterial sepsis †  1/169 (0.59%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Bronchitis †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Clostridium difficile infection †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Conjunctivitis viral †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Encephalitis †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Escherichia sepsis †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Nasopharyngitis †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Neutropenic sepsis †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Pneumonia streptococcal †  0/169 (0.00%)  1/178 (0.56%)  1/179 (0.56%)  0/45 (0.00%) 
Progressive multifocal leukoencephalopathy †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Pseudomonal sepsis †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Respiratory syncytial virus infection †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Respiratory tract infection †  1/169 (0.59%)  1/178 (0.56%)  2/179 (1.12%)  0/45 (0.00%) 
Soft tissue infection †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Streptococcal bacteraemia †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Vascular access site infection †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Viral infection †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Wound infection †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Aspergillus infection †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Bacteraemia †  1/169 (0.59%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Bronchopulmonary aspergillosis †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Bursitis infective †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Dacryocystitis †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Disseminated cryptococcosis †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Diverticulitis †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Gastroenteritis †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Kidney infection †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Klebsiella sepsis †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Lung infection †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Otitis externa †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Parainfluenzae virus infection †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Pneumonia bacterial †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Septic shock †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Upper respiratory tract infection †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  1/45 (2.22%) 
Vestibular neuronitis †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Injury, poisoning and procedural complications         
Infusion related reaction †  2/169 (1.18%)  4/178 (2.25%)  0/179 (0.00%)  0/45 (0.00%) 
Fall †  1/169 (0.59%)  2/178 (1.12%)  2/179 (1.12%)  0/45 (0.00%) 
Femoral neck fracture †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Post procedural haemorrhage †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Subdural haemorrhage †  1/169 (0.59%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Urinary retention postoperative †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Costal cartilage fracture †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Femur fracture †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Joint dislocation †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Lumbar vertebral fracture †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Post-traumatic neck syndrome †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Upper limb fracture †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Investigations         
Haemoglobin decreased †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Blood bilirubin increased †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Metabolism and nutrition disorders         
Pseudohyperkalaemia †  0/169 (0.00%)  1/178 (0.56%)  1/179 (0.56%)  0/45 (0.00%) 
Tumour lysis syndrome †  8/169 (4.73%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Fluid overload †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Hyperkalaemia †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Hyponatraemia †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Musculoskeletal and connective tissue disorders         
Osteoarthritis †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  1/45 (2.22%) 
Back pain †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Costochondritis †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Haemarthrosis †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Muscle spasms †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Myositis †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Basal cell carcinoma †  0/169 (0.00%)  2/178 (1.12%)  1/179 (0.56%)  0/45 (0.00%) 
Squamous cell carcinoma †  0/169 (0.00%)  2/178 (1.12%)  0/179 (0.00%)  0/45 (0.00%) 
Gastric cancer stage IV †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Metastases to bone †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Non-small cell lung cancer †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Prostate cancer †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Renal cell carcinoma †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Squamous cell carcinoma of skin †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Acute myelomonocytic leukaemia †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Adenoma benign †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Brain neoplasm †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Glioblastoma †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Lung adenocarcinoma †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Tumour ulceration †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Malignant melanoma †  0/169 (0.00%)  0/178 (0.00%)  0/179 (0.00%)  1/45 (2.22%) 
Nodular melanoma †  0/169 (0.00%)  0/178 (0.00%)  0/179 (0.00%)  1/45 (2.22%) 
Nervous system disorders         
Ischaemic stroke †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Presyncope †  1/169 (0.59%)  1/178 (0.56%)  1/179 (0.56%)  0/45 (0.00%) 
Syncope †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Transient ischaemic attack †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Brain injury †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Cerebral ischaemia †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Ischaemic cerebral infarction †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Parkinson's disease †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Haemorrhage intracranial †  0/169 (0.00%)  0/178 (0.00%)  0/179 (0.00%)  1/45 (2.22%) 
Psychiatric disorders         
Delirium †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Renal and urinary disorders         
Acute kidney injury †  1/169 (0.59%)  2/178 (1.12%)  0/179 (0.00%)  0/45 (0.00%) 
Calculus urinary †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Renal colic †  0/169 (0.00%)  1/178 (0.56%)  1/179 (0.56%)  0/45 (0.00%) 
Hydronephrosis †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Ureterolithiasis †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Reproductive system and breast disorders         
Benign prostatic hyperplasia †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Chronic obstructive pulmonary disease †  0/169 (0.00%)  2/178 (1.12%)  0/179 (0.00%)  0/45 (0.00%) 
Pulmonary embolism †  1/169 (0.59%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Tonsillar cyst †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Acute respiratory failure †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Asthma †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Dyspnoea †  0/169 (0.00%)  0/178 (0.00%)  3/179 (1.68%)  0/45 (0.00%) 
Haemoptysis †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Hypoxia †  2/169 (1.18%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Interstitial lung disease †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Pleural effusion †  2/169 (1.18%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Pulmonary oedema †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Skin and subcutaneous tissue disorders         
Skin ulcer †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Vascular disorders         
Deep vein thrombosis †  0/169 (0.00%)  1/178 (0.56%)  0/179 (0.00%)  0/45 (0.00%) 
Aortic stenosis †  1/169 (0.59%)  0/178 (0.00%)  0/179 (0.00%)  0/45 (0.00%) 
Hypertension †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
Hypotension †  0/169 (0.00%)  0/178 (0.00%)  1/179 (0.56%)  0/45 (0.00%) 
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A: Obinutuzumab in Combination With Chlorambucil Arm B: Acalabrutinib in Combination With Obinutuzumab Arm C: Acalabrutinib Monotherapy Arm A Cross-over: Obinutuzumab+Chlorambucil Crossover to Acalabrutinib Monotherapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   167/169 (98.82%)   171/178 (96.07%)   170/179 (94.97%)   37/45 (82.22%) 
Blood and lymphatic system disorders         
Neutropenia †  76/169 (44.97%)  56/178 (31.46%)  19/179 (10.61%)  1/45 (2.22%) 
Thrombocytopenia †  24/169 (14.20%)  23/178 (12.92%)  13/179 (7.26%)  3/45 (6.67%) 
Anaemia †  20/169 (11.83%)  21/178 (11.80%)  25/179 (13.97%)  0/45 (0.00%) 
Gastrointestinal disorders         
Diarrhoea †  36/169 (21.30%)  69/178 (38.76%)  62/179 (34.64%)  8/45 (17.78%) 
Nausea †  53/169 (31.36%)  36/178 (20.22%)  40/179 (22.35%)  9/45 (20.00%) 
Constipation †  17/169 (10.06%)  25/178 (14.04%)  20/179 (11.17%)  5/45 (11.11%) 
Vomiting †  19/169 (11.24%)  24/178 (13.48%)  22/179 (12.29%)  2/45 (4.44%) 
Abdominal pain †  12/169 (7.10%)  11/178 (6.18%)  9/179 (5.03%)  3/45 (6.67%) 
Abdominal pain upper †  4/169 (2.37%)  11/178 (6.18%)  8/179 (4.47%)  1/45 (2.22%) 
Dyspepsia †  8/169 (4.73%)  9/178 (5.06%)  14/179 (7.82%)  2/45 (4.44%) 
Gastrooesophageal reflux disease †  6/169 (3.55%)  3/178 (1.69%)  11/179 (6.15%)  2/45 (4.44%) 
General disorders         
Fatigue †  29/169 (17.16%)  50/178 (28.09%)  33/179 (18.44%)  6/45 (13.33%) 
Pyrexia †  35/169 (20.71%)  23/178 (12.92%)  12/179 (6.70%)  5/45 (11.11%) 
Oedema peripheral †  12/169 (7.10%)  22/178 (12.36%)  16/179 (8.94%)  3/45 (6.67%) 
Chills †  14/169 (8.28%)  20/178 (11.24%)  8/179 (4.47%)  0/45 (0.00%) 
Asthenia †  10/169 (5.92%)  17/178 (9.55%)  9/179 (5.03%)  1/45 (2.22%) 
Peripheral swelling †  4/169 (2.37%)  9/178 (5.06%)  9/179 (5.03%)  2/45 (4.44%) 
Influenza like illness †  4/169 (2.37%)  8/178 (4.49%)  12/179 (6.70%)  1/45 (2.22%) 
Infections and infestations         
Upper respiratory tract infection †  14/169 (8.28%)  38/178 (21.35%)  33/179 (18.44%)  6/45 (13.33%) 
Urinary tract infection †  8/169 (4.73%)  22/178 (12.36%)  22/179 (12.29%)  3/45 (6.67%) 
Nasopharyngitis †  7/169 (4.14%)  20/178 (11.24%)  17/179 (9.50%)  4/45 (8.89%) 
Sinusitis †  6/169 (3.55%)  16/178 (8.99%)  12/179 (6.70%)  0/45 (0.00%) 
Bronchitis †  5/169 (2.96%)  15/178 (8.43%)  14/179 (7.82%)  2/45 (4.44%) 
Pneumonia †  5/169 (2.96%)  19/178 (10.67%)  13/179 (7.26%)  1/45 (2.22%) 
Herpes zoster †  4/169 (2.37%)  11/178 (6.18%)  5/179 (2.79%)  1/45 (2.22%) 
Injury, poisoning and procedural complications         
Contusion †  7/169 (4.14%)  42/178 (23.60%)  27/179 (15.08%)  5/45 (11.11%) 
Infusion related reaction †  67/169 (39.64%)  24/178 (13.48%)  0/179 (0.00%)  1/45 (2.22%) 
Fall †  4/169 (2.37%)  14/178 (7.87%)  11/179 (6.15%)  0/45 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite †  13/169 (7.69%)  18/178 (10.11%)  10/179 (5.59%)  2/45 (4.44%) 
Hypokalaemia †  2/169 (1.18%)  12/178 (6.74%)  2/179 (1.12%)  0/45 (0.00%) 
Hyperglycaemia †  5/169 (2.96%)  9/178 (5.06%)  2/179 (1.12%)  0/45 (0.00%) 
Hyperuricaemia †  9/169 (5.33%)  8/178 (4.49%)  4/179 (2.23%)  1/45 (2.22%) 
Musculoskeletal and connective tissue disorders         
Arthralgia †  8/169 (4.73%)  39/178 (21.91%)  28/179 (15.64%)  3/45 (6.67%) 
Back pain †  14/169 (8.28%)  25/178 (14.04%)  25/179 (13.97%)  4/45 (8.89%) 
Pain in extremity †  7/169 (4.14%)  22/178 (12.36%)  11/179 (6.15%)  3/45 (6.67%) 
Myalgia †  4/169 (2.37%)  14/178 (7.87%)  15/179 (8.38%)  0/45 (0.00%) 
Musculoskeletal pain †  3/169 (1.78%)  13/178 (7.30%)  10/179 (5.59%)  2/45 (4.44%) 
Neck pain †  2/169 (1.18%)  9/178 (5.06%)  10/179 (5.59%)  1/45 (2.22%) 
Nervous system disorders         
Headache †  20/169 (11.83%)  71/178 (39.89%)  66/179 (36.87%)  10/45 (22.22%) 
Dizziness †  10/169 (5.92%)  32/178 (17.98%)  21/179 (11.73%)  4/45 (8.89%) 
Paraesthesia †  4/169 (2.37%)  10/178 (5.62%)  5/179 (2.79%)  0/45 (0.00%) 
Psychiatric disorders         
Insomnia †  16/169 (9.47%)  16/178 (8.99%)  15/179 (8.38%)  3/45 (6.67%) 
Anxiety †  5/169 (2.96%)  9/178 (5.06%)  4/179 (2.23%)  0/45 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough †  15/169 (8.88%)  39/178 (21.91%)  33/179 (18.44%)  7/45 (15.56%) 
Dyspnoea †  17/169 (10.06%)  15/178 (8.43%)  12/179 (6.70%)  2/45 (4.44%) 
Epistaxis †  2/169 (1.18%)  13/178 (7.30%)  10/179 (5.59%)  1/45 (2.22%) 
Oropharyngeal pain †  2/169 (1.18%)  13/178 (7.30%)  8/179 (4.47%)  0/45 (0.00%) 
Productive cough †  4/169 (2.37%)  5/178 (2.81%)  12/179 (6.70%)  1/45 (2.22%) 
Skin and subcutaneous tissue disorders         
Rash †  8/169 (4.73%)  21/178 (11.80%)  25/179 (13.97%)  4/45 (8.89%) 
Petechiae †  0/169 (0.00%)  14/178 (7.87%)  16/179 (8.94%)  1/45 (2.22%) 
Pruritus †  6/169 (3.55%)  11/178 (6.18%)  15/179 (8.38%)  1/45 (2.22%) 
Erythema †  2/169 (1.18%)  7/178 (3.93%)  9/179 (5.03%)  0/45 (0.00%) 
Vascular disorders         
Hypotension †  5/169 (2.96%)  14/178 (7.87%)  6/179 (3.35%)  1/45 (2.22%) 
Hypertension †  6/169 (3.55%)  11/178 (6.18%)  8/179 (4.47%)  1/45 (2.22%) 
Haematoma †  1/169 (0.59%)  9/178 (5.06%)  7/179 (3.91%)  2/45 (4.44%) 
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Institution/Investigator will not publish or publicly present any study results without prior approval or prior to 12 months following completion of the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Acerta Clinical Trials
Phone: 18882929613
EMail: acertamc@dlss.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Acerta Pharma BV
ClinicalTrials.gov Identifier: NCT02475681    
Other Study ID Numbers: ACE-CL-007
2014-005582-73 ( EudraCT Number )
First Submitted: June 12, 2015
First Posted: June 19, 2015
Results First Submitted: February 28, 2020
Results First Posted: January 10, 2023
Last Update Posted: March 4, 2024