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A Study of the Combination of Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for the First-line Treatment of Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (GLOW)

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ClinicalTrials.gov Identifier: NCT03462719
Recruitment Status : Active, not recruiting
First Posted : March 12, 2018
Results First Posted : March 28, 2022
Last Update Posted : October 7, 2022
Sponsor:
Collaborator:
Pharmacyclics LLC.
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukemia, Lymphocytic, Chronic, B-Cell
Interventions Drug: Ibrutinib
Drug: Venetoclax
Drug: Chlorambucil
Drug: Obinutuzumab
Drug: Ibrutinib (as Subsequent Therapy)
Enrollment 211
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Hide Arm/Group Description Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity. Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Period Title: Overall Study
Started 106 105
Completed 11 11
Not Completed 95 94
Reason Not Completed
Withdrawal by Subject             2             3
Ongoing             93             91
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab) Total
Hide Arm/Group Description Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity. Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity. Total of all reporting groups
Overall Number of Baseline Participants 106 105 211
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 106 participants 105 participants 211 participants
71  (8.02) 72  (6.16) 71.5  (7.01)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 105 participants 211 participants
Female
47
  44.3%
42
  40.0%
89
  42.2%
Male
59
  55.7%
63
  60.0%
122
  57.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 105 participants 211 participants
Hispanic or Latino
1
   0.9%
3
   2.9%
4
   1.9%
Not Hispanic or Latino
101
  95.3%
99
  94.3%
200
  94.8%
Unknown or Not Reported
4
   3.8%
3
   2.9%
7
   3.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 105 participants 211 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   1.0%
1
   0.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
101
  95.3%
101
  96.2%
202
  95.7%
More than one race
1
   0.9%
0
   0.0%
1
   0.5%
Unknown or Not Reported
4
   3.8%
3
   2.9%
7
   3.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 105 participants 211 participants
BELGIUM
7
   6.6%
2
   1.9%
9
   4.3%
CANADA
7
   6.6%
10
   9.5%
17
   8.1%
CZECH REPUBLIC
9
   8.5%
13
  12.4%
22
  10.4%
DENMARK
7
   6.6%
5
   4.8%
12
   5.7%
FRANCE
4
   3.8%
3
   2.9%
7
   3.3%
ISRAEL
6
   5.7%
12
  11.4%
18
   8.5%
NETHERLANDS
1
   0.9%
6
   5.7%
7
   3.3%
POLAND
12
  11.3%
10
   9.5%
22
  10.4%
RUSSIAN FEDERATION
23
  21.7%
16
  15.2%
39
  18.5%
SPAIN
10
   9.4%
9
   8.6%
19
   9.0%
SWEDEN
2
   1.9%
0
   0.0%
2
   0.9%
TURKEY
8
   7.5%
13
  12.4%
21
  10.0%
UNITED KINGDOM
8
   7.5%
4
   3.8%
12
   5.7%
UNITED STATES
2
   1.9%
2
   1.9%
4
   1.9%
1.Primary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS: time between date of randomization and date of disease progression, as assessed by IRC, or date of death due to any cause, whichever occurs first, regardless of use of subsequent anti-cancer therapy prior to PD or death using iWCLL2008 criteria : New enlarged lymph nodes >15 mm, new hepatomegaly or splenomegaly, or other organ infiltrates, bone lesion, ascites or pleural effusion due to CLL; >=50% increase in longest diameter (LDi) from nadir in existing lymph node (LDi >15 mm) or >=50% increase from nadir in sum of diameters of multiple nodes (and at least 1 node with LDi >15 mm); >=50% increase from nadir in enlargement of liver/spleen; >=50% increase from baseline in lymphocyte count (ALC; to >=5*10^9/L); or >=50% increase from nadir in ALC in >=2 serial assessments if ALC is >=30000*10^9/L and lymphocyte doubling time is rapid unless considered treatment-related lymphocytosis; new cytopenia attributable to CLL; transformation to more aggressive histology.
Time Frame Up to 2 years 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Hide Arm/Group Description:
Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 106 105
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(31.24 to NA)
20.96
(16.59 to 24.67)
[1]
Here "NA" indicates that median and upper limit of 95% CI was not estimable due to insufficient number of events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment Arm A (Ibrutinib + Venetoclax), Treatment Arm B (Chlorambucil + Obinutuzumab)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.216
Confidence Interval (2-Sided) 95%
0.131 to 0.357
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Minimal Residual Disease (MRD) Negative Rate
Hide Description MRD-negative rate is defined as the percentage of participants who achieved MRD-negative status (that is, less than [<] 1 chronic lymphocytic leukemia (CLL) cell per 10,000 leukocytes or <0.01 percentage [%]) in the bone marrow as assessed by next-generation sequencing (NGS). Participants with missing MRD data were considered MRD positive.
Time Frame Up to 2 years 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Hide Arm/Group Description:
Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 106 105
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
55.7
(46.2 to 65.1)
21.0
(13.2 to 28.7)
3.Secondary Outcome
Title Complete Response Rate (CRR)
Hide Description Complete response rate is defined as the percentage of participants who achieved complete response or complete response with an incomplete marrow recovery (CRi) on or prior to initiation of subsequent anti-leukemic therapy per the IRC assessment. International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils >1.5*10^9/liter (L), platelets >100*10^9/L, Hgb >11 gram per deciliter (g/dL), absolute lymphocyte count <4000/microliter (mcL) and normocellular bone marrow with <30% lymphocytes and no B lymphoid nodules; CRi- CR with incomplete recovery of bone marrow.
Time Frame Up to 2 years 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Hide Arm/Group Description:
Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 106 105
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
38.7
(29.4 to 48.0)
11.4
(5.3 to 17.5)
4.Secondary Outcome
Title Overall Response Rate (ORR)
Hide Description ORR: percentage of participants who achieved best overall response of either CR, CRi, nodular PR (nPR) and partial response (PR). iWCLL 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils >1.5*10^9/liter (L), platelets >100*10^9/L, Hgb >11 g/dL and ALC <4000/mcL, normocellular bone marrow with <30% lymphocytes and no B lymphoid nodules; CRi- CR with incomplete recovery of bone marrow; nPR- participants meet criteria for CR, but bone marrow biopsy shows B-lymphoid nodules (reflecting residual disease); PR-2 of following when abnormal at baseline: >=50% decrease in ALC, >=50% decrease in sum of products of multiple nodes, >=50% decrease in enlargement of spleen or liver; and 1 of following: neutrophils >1.5*10^9/L, Platelets >100*10^9/L and Hgb>11 g/dL or >=50% improvement over baseline in any of these; 50% reduction in bone marrow infiltrates or B lymphoid nodules; no new enlarged nodes or new hepatosplenomegaly.
Time Frame Up to 2 years 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. Participants with missing post-randomization data were considered non-responders.
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Hide Arm/Group Description:
Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 106 105
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
86.8
(80.3 to 93.2)
84.8
(77.9 to 91.6)
5.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS is defined as the time from date of randomization to date of death from any cause.
Time Frame Up to 3 years 4 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Hide Arm/Group Description:
Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 11 16
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Here "NA" indicates that median and 95% CI was not estimable due to insufficient number of events.
6.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR is defined as the interval between the date of initial documentation of a response including partial response with lymphocytosis (PRL) and the date of first documented evidence of PD or death or date of censoring per the IRC assessment. iWCLL 2008 criteria for PD: New enlarged nodes >1.5 cm, new hepatomegaly or splenomegaly, or other organ infiltrates; >= 50% increase from nadir in existing lymph node or >=50% increase from nadir in sum of product of diameters of multiple nodes; >=50% increase from nadir in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (and to >=5*10^9/L) unless considered treatment-related lymphocytosis; new cytopenia (Hemoglobin b or platelets) attributable to CLL; transformation to a more aggressive histology.
Time Frame Up to 2 years 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
Population analyzed included ITT amongst who were responders (PR or better).
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Hide Arm/Group Description:
Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 92 89
Median (95% Confidence Interval)
Unit of Measure: Months
28.85 [1] 
(28.68 to NA)
21.13
(15.93 to 25.10)
[1]
Here "NA" indicates that upper limit of 95% CI was not estimable due to insufficient number of events.
7.Secondary Outcome
Title Time-to-Next Treatment
Hide Description Time-to-next treatment was measured from the date of randomization to the start date of any subsequent anti-leukemic therapy.
Time Frame Up to 2 years 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Hide Arm/Group Description:
Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 106 105
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [2] 
(31.54 to NA)
[1]
Here "NA" indicates that median and 95% CI was not estimable due to insufficient number of events.
[2]
Here "NA" indicates that median and upper limit of 95% CI was not estimable due to insufficient number of events.
8.Secondary Outcome
Title Time to Worsening as Measured by Using EuroQol 5 Dimension 5 Level Questionnaire (EQ-5D-5L)
Hide Description

Time to worsening= time interval (months) from randomization to first observation of deterioration. EQ-5D-5L consists of a 5-item descriptive system and the EuroQol visual analog scale (EQ-5D VAS). EQ-5D-VAS self-rating records respondent's own assessment of his/her overall health status at time of completion, on scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Worsening is defined as a decrease of >= 7 points (on a 0-100 scale).

EQ-5D-5L descriptive system comprises 5 dimensions of health (mobility, self -care, usual activities, pain/discomfort, and anxiety/depression) to describe participant's current health state. Responses for 5 dimensions are combined into a 5-digit number describing respondents health state that can be converted into a single index value or utility score (using the United Kingdom weights), ranging from -1 to 1, where lower scores indicate a worse health status. Worsening is defined as a decrease of >=0.08 points (on a 0-1 scale).

Time Frame Up to 2 years 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Hide Arm/Group Description:
Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 106 105
Median (95% Confidence Interval)
Unit of Measure: Months
EQ-5D-5L: Visual Analogue Score
8.34 [1] 
(5.65 to NA)
24.18 [1] 
(11.27 to NA)
EQ-5D-5L: Utility Score
14.29 [1] 
(8.15 to NA)
24.11 [1] 
(8.34 to NA)
[1]
Here "NA" indicates that upper limit of 95% CI was not estimable due to insufficient number of events.
9.Secondary Outcome
Title Time to Worsening Measured by European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC QLQ)-C30)
Hide Description Time to worsening= time interval from randomization to first observation of deterioration. EORTC QLQ-C30 includes 30 separate items: 5 functional scales (physical, role, emotional, cognitive, and social Functioning), 1 global health status (GHS) and QoL scale, 3 symptom scales (fatigue, nausea/vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Each item, except GHS, is answered on 4-point scale (1=not at all to 4=very much) and GHS is measured on 1-7 scale: 1=very poor and 7=excellent. Scores derived using validated scoring algorithms as per EORTC QLQ-C30 Manual and linearly transformed in a range from 0-100. For functional and global QoL scales, higher scores=better level of functioning/QoL. For symptom-oriented scales, higher score=more severe symptoms. Worsening in functional and global health scores=decrease of >=10 points (on 0-100 scale) and in symptom scores=increase of >=10 points (on 0-100 scale).
Time Frame Up to 2 years 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Hide Arm/Group Description:
Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 106 105
Median (95% Confidence Interval)
Unit of Measure: Months
Global Health Status
14.95 [1] 
(8.38 to NA)
24.18 [1] 
(13.86 to NA)
Cognitive Functioning
11.07
(5.95 to 24.05)
14.03 [1] 
(7.16 to NA)
Emotional Functioning
NA [2] 
(17.31 to NA)
25.00 [3] 
(16.62 to NA)
Physical Functioning
NA [2] 
(19.42 to NA)
NA [2] 
(14.03 to NA)
Role Functioning
11.10
(6.28 to 14.95)
8.48
(5.62 to 16.69)
Social Functioning
11.10
(8.34 to 16.69)
17.87
(11.07 to 25.30)
Fatigue (Symptom Scale)
8.38
(5.62 to 14.95)
17.87 [1] 
(8.44 to NA)
Nausea/Vomiting (Symptom Scale)
11.07 [1] 
(8.28 to NA)
NA [2] 
(20.44 to NA)
Pain (Symptom Scale)
8.31
(5.45 to 13.90)
11.01
(5.65 to 17.87)
[1]
Here "NA" indicates that upper limit of 95% CI was not estimable due to insufficient number of events.
[2]
Here "NA" indicates that median and upper limit of 95% CI was not estimable due to insufficient number of events.
[3]
Here "NA" indicates that upper limit of 95% CI was not estimable due to insufficient number of events
10.Secondary Outcome
Title Time to Worsening and Time to Improvement as Measured by Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score
Hide Description Responses to the 13-item FACIT Fatigue Scale are reported on a 5-point categorical response scale ranging from 0 (not at all) to 4 (very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worst score) to 52 (best score). Time to Worsening is defined as time interval (months) from randomization to first observation of deterioration. Worsening is defined as a decrease >= 3 points (on a 0-52 scale). Time to improvement is defined as the time interval (months) from randomization to the first observation of improvement. Improvement is defined as an increase >=3 points (on a 0-52 scale).
Time Frame Up to 2 years 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Hide Arm/Group Description:
Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 106 105
Median (95% Confidence Interval)
Unit of Measure: Months
Time to Worsening
8.15
(3.98 to 10.94)
14.03 [1] 
(8.61 to NA)
Time to Improvement
5.59
(3.81 to 11.20)
3.75
(2.20 to 5.75)
[1]
Here "NA" indicates that upper limit of 95% CI was not estimable due to insufficient number of events.
11.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
Hide Description An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Time Frame Up to 3 years 4 months
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set is defined as all randomized participants who received at least one dose of any one of the four study drugs (ibrutinib, venetoclax, chlorambucil, or obinutuzumab).
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Hide Arm/Group Description:
Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 106 105
Measure Type: Count of Participants
Unit of Measure: Participants
105
  99.1%
99
  94.3%
12.Secondary Outcome
Title Number of Participants With Abnormal Clinical Laboratory Findings
Hide Description Number of participants with abnormal clinical laboratory findings (hematology and serum chemistry) were reported.
Time Frame Up to 2 years 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set is defined as all randomized participants who received at least one dose of any one of the four study drugs (ibrutinib, venetoclax, chlorambucil, or obinutuzumab).
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Hide Arm/Group Description:
Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 106 105
Measure Type: Count of Participants
Unit of Measure: Participants
Hematology: Absolute Neutrophils Counts (Decrease)
81
  76.4%
95
  90.5%
Hematology: Hemoglobin (Decrease)
38
  35.8%
42
  40.0%
Hematology: Platelets (Decrease)
52
  49.1%
78
  74.3%
Hematology: Any hemoglobin, platelet, or ANC decrease
94
  88.7%
103
  98.1%
Chemistry: Alanine Transaminase (ALT) (Increase)
22
  20.8%
26
  24.8%
Chemistry: Aspartate Aminotransferase (AST) (Increase)
23
  21.7%
30
  28.6%
Chemistry: Alkaline Phosphatase (Increase)
19
  17.9%
21
  20.0%
Chemistry: Bilirubin (Increase)
36
  34.0%
25
  23.8%
Chemistry: Creatinine (Increase)
33
  31.1%
17
  16.2%
Chemistry: Creatinine Clearance (Decrease)
40
  37.7%
17
  16.2%
Chemistry: Hypercalcemia
13
  12.3%
3
   2.9%
Chemistry: Hypoalbuminemia
36
  34.0%
20
  19.0%
Chemistry: Hypocalcemia
27
  25.5%
30
  28.6%
Chemistry: Phosphate (Decrease)
16
  15.1%
6
   5.7%
Chemistry: Potassium (Decrease)
25
  23.6%
9
   8.6%
Chemistry: Potassium (Increase)
31
  29.2%
22
  21.0%
Chemistry: Sodium (Decrease)
25
  23.6%
26
  24.8%
Chemistry: Sodium (Increase)
12
  11.3%
8
   7.6%
Chemistry: Uric Acid (Increase)
37
  34.9%
19
  18.1%
13.Secondary Outcome
Title Percentage of Participants With Sustained Hemoglobin Improvement
Hide Description Sustained hemoglobin improvement is defined as the percentage of participants who achieved an increase in hemoglobin levels from baseline by >= 2 grams per deciliter (g/dL) and lasts for at least 56 days without blood transfusion or growth factors.
Time Frame Up to 2 years 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Hide Arm/Group Description:
Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 106 105
Measure Type: Number
Unit of Measure: Percentage of Participants
44.3 50.5
14.Secondary Outcome
Title Percentage of Participants With Sustained Platelet Improvement
Hide Description Sustained platelet improvement is defined as the percentage of participants who achieved an increase in platelet levels from baseline by >= 50% and lasts for at least 56 days without blood transfusion or growth factors.
Time Frame Up to 2 years 10 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT analysis set included all randomized participants who were analyzed according to assigned treatment group, regardless of the actual treatment received.
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Hide Arm/Group Description:
Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 106 105
Measure Type: Number
Unit of Measure: Percentage of Participants
24.5 29.5
15.Secondary Outcome
Title Plasma Concentration of Ibrutinib and Venetoclax
Hide Description Plasma concentrations of ibrutinib and venetoclax were determined by validated liquid chromatography-tandem mass spectrometry.
Time Frame Ibrutinib: Pre-dose-Day 1 of Cycles 2, 3, 5 and 6 (each cycle is defined as 28 days), Venetoclax: Pre-dose-Day 1 of Cycles 5 and 6
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetics (PK) analysis set is defined as all randomized participants in Treatment Arm A who received at least one dose of ibrutinib and/or venetoclax and had at least one valid blood sample drawn for PK analysis. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this endpoint. Here, "n (number analyzed)" is defined as number of participants analyzed for specified category.
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax)
Hide Arm/Group Description:
Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 79
Mean (Standard Deviation)
Unit of Measure: Nanograms per milliliter (ng/mL)
Ibrutinib: Pre-dose Day 1 Cycle 2 (Ibrutinib Alone) Number Analyzed 63 participants
5.70  (5.58)
Ibrutinib: Pre-dose Day 1 Cycle 3 (Ibrutinib Alone) Number Analyzed 59 participants
6.20  (7.78)
Ibrutinib: Pre-dose Day 1 Cycle 5 (Ibrutinib and Venetoclax) Number Analyzed 65 participants
6.37  (6.71)
Ibrutinib: Pre-dose Day 1 Cycle 6 (Ibrutinib and Venetoclax) Number Analyzed 60 participants
5.90  (6.74)
Venetoclax: Pre-dose Day 1 Cycle 5 (Ibrutinib + Venetoclax) Number Analyzed 79 participants
1139  (959)
Venetoclax: Pre-dose Day 1 Cycle 6 (Ibrutinib + Venetoclax) Number Analyzed 65 participants
1765  (1573)
Time Frame Up to 3 years 4 months
Adverse Event Reporting Description The safety analysis set is defined as all randomized participants who received at least one dose of any one of the four study drugs (ibrutinib, venetoclax, chlorambucil, or obinutuzumab).
 
Arm/Group Title Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Hide Arm/Group Description Participants received ibrutinib 420 milligrams (mg) orally once daily for 3 cycles (each cycle is of 28 days) followed by the combination of ibrutinib 420 mg and venetoclax 400 mg orally once daily for 12 cycles (including a 5-week venetoclax dose ramp up starting in cycle 4). Participants who subsequently developed independent review committee (IRC)-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity. Participants received chlorambucil 0.5 milligrams per kilogram (mg/kg) body weight orally once daily on Days 1 and 15 of Cycles 1 to 6 in combination with obinutuzumab 1000 mgs intravenously (IV) once daily on Days 1, 8, and 15 of Cycle 1 and Day 1 of Cycles 2 to 6 (each cycle is of 28 days). Participants who subsequently developed IRC-confirmed progressive disease (PD) and had active disease requiring treatment were eligible to participate in the Subsequent Therapy Phase and received single-agent ibrutinib until disease progression or unacceptable toxicity.
All-Cause Mortality
Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Affected / at Risk (%) Affected / at Risk (%)
Total   11/106 (10.38%)   16/105 (15.24%) 
Hide Serious Adverse Events
Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Affected / at Risk (%) Affected / at Risk (%)
Total   49/106 (46.23%)   30/105 (28.57%) 
Blood and lymphatic system disorders     
Anaemia * 1  3/106 (2.83%)  2/105 (1.90%) 
Febrile Neutropenia * 1  1/106 (0.94%)  3/105 (2.86%) 
Neutropenia * 1  2/106 (1.89%)  1/105 (0.95%) 
Cardiac disorders     
Acute Myocardial Infarction * 1  2/106 (1.89%)  1/105 (0.95%) 
Angina Unstable * 1  1/106 (0.94%)  0/105 (0.00%) 
Atrial Fibrillation * 1  7/106 (6.60%)  0/105 (0.00%) 
Cardiac Arrest * 1  1/106 (0.94%)  0/105 (0.00%) 
Cardiac Failure * 1  3/106 (2.83%)  0/105 (0.00%) 
Cardiac Failure Congestive * 1  0/106 (0.00%)  1/105 (0.95%) 
Myocardial Infarction * 1  1/106 (0.94%)  0/105 (0.00%) 
Sinus Node Dysfunction * 1  2/106 (1.89%)  0/105 (0.00%) 
Supraventricular Tachycardia * 1  0/106 (0.00%)  1/105 (0.95%) 
Gastrointestinal disorders     
Diarrhoea * 1  3/106 (2.83%)  1/105 (0.95%) 
Gastritis * 1  1/106 (0.94%)  0/105 (0.00%) 
Mesenteric Artery Thrombosis * 1  1/106 (0.94%)  0/105 (0.00%) 
Oesophagitis * 1  0/106 (0.00%)  1/105 (0.95%) 
General disorders     
Asthenia * 1  1/106 (0.94%)  0/105 (0.00%) 
Oedema Peripheral * 1  2/106 (1.89%)  0/105 (0.00%) 
Pyrexia * 1  1/106 (0.94%)  2/105 (1.90%) 
Sudden Death * 1  2/106 (1.89%)  0/105 (0.00%) 
Hepatobiliary disorders     
Cholecystitis Acute * 1  1/106 (0.94%)  0/105 (0.00%) 
Cholecystitis Chronic * 1  1/106 (0.94%)  0/105 (0.00%) 
Cholestasis * 1  0/106 (0.00%)  1/105 (0.95%) 
Gallbladder Rupture * 1  0/106 (0.00%)  1/105 (0.95%) 
Immune system disorders     
Cytokine Release Syndrome * 1  0/106 (0.00%)  1/105 (0.95%) 
Infections and infestations     
Bronchitis * 1  1/106 (0.94%)  0/105 (0.00%) 
Bronchopulmonary Aspergillosis * 1  1/106 (0.94%)  0/105 (0.00%) 
Cellulitis * 1  1/106 (0.94%)  0/105 (0.00%) 
Clostridium Colitis * 1  1/106 (0.94%)  0/105 (0.00%) 
Covid-19 Pneumonia * 1  0/106 (0.00%)  0/105 (0.00%) 
Erysipelas * 1  1/106 (0.94%)  0/105 (0.00%) 
Escherichia Urinary Tract Infection * 1  0/106 (0.00%)  1/105 (0.95%) 
Gastroenteritis * 1  1/106 (0.94%)  0/105 (0.00%) 
Gastrointestinal Infection * 1  1/106 (0.94%)  0/105 (0.00%) 
Infection * 1  1/106 (0.94%)  0/105 (0.00%) 
Influenza * 1  1/106 (0.94%)  0/105 (0.00%) 
Pneumococcal Sepsis * 1  0/106 (0.00%)  1/105 (0.95%) 
Pneumonia * 1  6/106 (5.66%)  6/105 (5.71%) 
Pneumonia Cytomegaloviral * 1  1/106 (0.94%)  0/105 (0.00%) 
Respiratory Tract Infection * 1  0/106 (0.00%)  1/105 (0.95%) 
Septic Shock * 1  1/106 (0.94%)  0/105 (0.00%) 
Tonsillitis * 1  1/106 (0.94%)  0/105 (0.00%) 
Urinary Tract Infection * 1  0/106 (0.00%)  1/105 (0.95%) 
Injury, poisoning and procedural complications     
Fall * 1  1/106 (0.94%)  0/105 (0.00%) 
Femoral Neck Fracture * 1  1/106 (0.94%)  0/105 (0.00%) 
Hip Fracture * 1  1/106 (0.94%)  1/105 (0.95%) 
Infusion Related Reaction * 1  0/106 (0.00%)  3/105 (2.86%) 
Multiple Injuries * 1  0/106 (0.00%)  1/105 (0.95%) 
Overdose * 1  0/106 (0.00%)  2/105 (1.90%) 
Spinal Compression Fracture * 1  1/106 (0.94%)  0/105 (0.00%) 
Wound Necrosis * 1  1/106 (0.94%)  0/105 (0.00%) 
Investigations     
Alanine Aminotransferase Increased * 1  0/106 (0.00%)  2/105 (1.90%) 
Aspartate Aminotransferase Increased * 1  0/106 (0.00%)  1/105 (0.95%) 
Blood Phosphorus Increased * 1  0/106 (0.00%)  1/105 (0.95%) 
Neutrophil Count Decreased * 1  1/106 (0.94%)  0/105 (0.00%) 
Metabolism and nutrition disorders     
Hyperkalaemia * 1  1/106 (0.94%)  0/105 (0.00%) 
Hyperphosphataemia * 1  2/106 (1.89%)  0/105 (0.00%) 
Iron Deficiency * 1  0/106 (0.00%)  1/105 (0.95%) 
Tumour Lysis Syndrome * 1  0/106 (0.00%)  3/105 (2.86%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal Chest Pain * 1  1/106 (0.94%)  0/105 (0.00%) 
Polyarthritis * 1  1/106 (0.94%)  0/105 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma Gastric * 1  0/106 (0.00%)  1/105 (0.95%) 
Hepatocellular Carcinoma * 1  1/106 (0.94%)  0/105 (0.00%) 
Lung Neoplasm Malignant * 1  1/106 (0.94%)  0/105 (0.00%) 
Myelodysplastic Syndrome * 1  0/106 (0.00%)  1/105 (0.95%) 
Myeloproliferative Neoplasm * 1  0/106 (0.00%)  1/105 (0.95%) 
Neoplasm Malignant * 1  1/106 (0.94%)  0/105 (0.00%) 
Uterine Leiomyoma * 1  1/106 (0.94%)  0/105 (0.00%) 
Nervous system disorders     
Cerebral Haemorrhage * 1  1/106 (0.94%)  0/105 (0.00%) 
Dizziness * 1  1/106 (0.94%)  0/105 (0.00%) 
Ischaemic Stroke * 1  2/106 (1.89%)  0/105 (0.00%) 
Spinal Cord Compression * 1  1/106 (0.94%)  0/105 (0.00%) 
Toxic Encephalopathy * 1  1/106 (0.94%)  0/105 (0.00%) 
Psychiatric disorders     
Depression * 1  1/106 (0.94%)  0/105 (0.00%) 
Major Depression * 1  1/106 (0.94%)  0/105 (0.00%) 
Mental Disorder * 1  1/106 (0.94%)  0/105 (0.00%) 
Renal and urinary disorders     
Acute Kidney Injury * 1  1/106 (0.94%)  0/105 (0.00%) 
Chronic Kidney Disease * 1  1/106 (0.94%)  0/105 (0.00%) 
Haematuria * 1  2/106 (1.89%)  0/105 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Chronic Obstructive Pulmonary Disease * 1  1/106 (0.94%)  0/105 (0.00%) 
Dyspnoea * 1  1/106 (0.94%)  1/105 (0.95%) 
Dyspnoea Exertional * 1  1/106 (0.94%)  0/105 (0.00%) 
Haemoptysis * 1  1/106 (0.94%)  0/105 (0.00%) 
Pneumothorax * 1  1/106 (0.94%)  0/105 (0.00%) 
Pulmonary Congestion * 1  1/106 (0.94%)  0/105 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis Bullous * 1  1/106 (0.94%)  0/105 (0.00%) 
Ecchymosis * 1  1/106 (0.94%)  0/105 (0.00%) 
Pyoderma Gangrenosum * 1  1/106 (0.94%)  0/105 (0.00%) 
Rash * 1  1/106 (0.94%)  0/105 (0.00%) 
Urticaria * 1  1/106 (0.94%)  0/105 (0.00%) 
Vascular disorders     
Hypertension * 1  1/106 (0.94%)  0/105 (0.00%) 
Hypertensive Urgency * 1  1/106 (0.94%)  0/105 (0.00%) 
Hypotension * 1  1/106 (0.94%)  0/105 (0.00%) 
Venous Thrombosis * 1  1/106 (0.94%)  0/105 (0.00%) 
1
Term from vocabulary, MedDRA Version 23.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment Arm A (Ibrutinib + Venetoclax) Treatment Arm B (Chlorambucil + Obinutuzumab)
Affected / at Risk (%) Affected / at Risk (%)
Total   98/106 (92.45%)   98/105 (93.33%) 
Blood and lymphatic system disorders     
Anaemia * 1  17/106 (16.04%)  18/105 (17.14%) 
Leukopenia * 1  1/106 (0.94%)  6/105 (5.71%) 
Neutropenia * 1  36/106 (33.96%)  56/105 (53.33%) 
Thrombocytopenia * 1  12/106 (11.32%)  28/105 (26.67%) 
Cardiac disorders     
Atrial Fibrillation * 1  12/106 (11.32%)  2/105 (1.90%) 
Palpitations * 1  6/106 (5.66%)  3/105 (2.86%) 
Ear and labyrinth disorders     
Vertigo * 1  8/106 (7.55%)  0/105 (0.00%) 
Gastrointestinal disorders     
Abdominal Pain * 1  2/106 (1.89%)  5/105 (4.76%) 
Constipation * 1  11/106 (10.38%)  7/105 (6.67%) 
Diarrhoea * 1  53/106 (50.00%)  13/105 (12.38%) 
Dyspepsia * 1  10/106 (9.43%)  3/105 (2.86%) 
Mouth Ulceration * 1  8/106 (7.55%)  0/105 (0.00%) 
Nausea * 1  28/106 (26.42%)  27/105 (25.71%) 
Vomiting * 1  15/106 (14.15%)  14/105 (13.33%) 
General disorders     
Asthenia * 1  9/106 (8.49%)  7/105 (6.67%) 
Chills * 1  2/106 (1.89%)  12/105 (11.43%) 
Fatigue * 1  16/106 (15.09%)  10/105 (9.52%) 
Oedema Peripheral * 1  15/106 (14.15%)  3/105 (2.86%) 
Pyrexia * 1  6/106 (5.66%)  18/105 (17.14%) 
Infections and infestations     
Bronchitis * 1  7/106 (6.60%)  7/105 (6.67%) 
Conjunctivitis * 1  7/106 (6.60%)  2/105 (1.90%) 
Nasopharyngitis * 1  4/106 (3.77%)  7/105 (6.67%) 
Pharyngitis * 1  6/106 (5.66%)  1/105 (0.95%) 
Pneumonia * 1  5/106 (4.72%)  6/105 (5.71%) 
Upper Respiratory Tract Infection * 1  13/106 (12.26%)  14/105 (13.33%) 
Urinary Tract Infection * 1  17/106 (16.04%)  4/105 (3.81%) 
Injury, poisoning and procedural complications     
Contusion * 1  5/106 (4.72%)  0/105 (0.00%) 
Infusion Related Reaction * 1  0/106 (0.00%)  28/105 (26.67%) 
Investigations     
Alanine Aminotransferase Increased * 1  3/106 (2.83%)  5/105 (4.76%) 
Aspartate Aminotransferase Increased * 1  3/106 (2.83%)  6/105 (5.71%) 
Neutrophil Count Decreased * 1  10/106 (9.43%)  9/105 (8.57%) 
Weight Decreased * 1  8/106 (7.55%)  1/105 (0.95%) 
Metabolism and nutrition disorders     
Decreased Appetite * 1  14/106 (13.21%)  6/105 (5.71%) 
Hyperkalaemia * 1  8/106 (7.55%)  5/105 (4.76%) 
Hyperphosphataemia * 1  9/106 (8.49%)  0/105 (0.00%) 
Hyperuricaemia * 1  6/106 (5.66%)  3/105 (2.86%) 
Hyponatraemia * 1  6/106 (5.66%)  1/105 (0.95%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  12/106 (11.32%)  7/105 (6.67%) 
Back Pain * 1  10/106 (9.43%)  7/105 (6.67%) 
Muscle Spasms * 1  9/106 (8.49%)  2/105 (1.90%) 
Myalgia * 1  7/106 (6.60%)  1/105 (0.95%) 
Pain in Extremity * 1  6/106 (5.66%)  8/105 (7.62%) 
Nervous system disorders     
Dizziness Postural * 1  4/106 (3.77%)  6/105 (5.71%) 
Headache * 1  7/106 (6.60%)  5/105 (4.76%) 
Psychiatric disorders     
Insomnia * 1  9/106 (8.49%)  5/105 (4.76%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  9/106 (8.49%)  11/105 (10.48%) 
Dyspnoea * 1  6/106 (5.66%)  8/105 (7.62%) 
Epistaxis * 1  12/106 (11.32%)  3/105 (2.86%) 
Skin and subcutaneous tissue disorders     
Hyperhidrosis * 1  1/106 (0.94%)  6/105 (5.71%) 
Onychoclasis * 1  7/106 (6.60%)  0/105 (0.00%) 
Pruritus * 1  8/106 (7.55%)  5/105 (4.76%) 
Rash * 1  17/106 (16.04%)  7/105 (6.67%) 
Vascular disorders     
Haematoma * 1  8/106 (7.55%)  2/105 (1.90%) 
Hypertension * 1  13/106 (12.26%)  5/105 (4.76%) 
Hypotension * 1  3/106 (2.83%)  10/105 (9.52%) 
1
Term from vocabulary, MedDRA Version 23.0
*
Indicates events were collected by non-systematic assessment
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.
If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: EXECUTIVE MEDICAL DIRECTOR
Organization: Janssen Research & Development, LLC
Phone: 844-434-4210
EMail: ClinicalTrialDisclosure@its.jnj.com
Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03462719    
Other Study ID Numbers: CR108428
2017-004699-77 ( EudraCT Number )
54179060CLL3011 ( Other Identifier: Janssen Research & Development, LLC )
First Submitted: March 6, 2018
First Posted: March 12, 2018
Results First Submitted: February 25, 2022
Results First Posted: March 28, 2022
Last Update Posted: October 7, 2022