Comparison of the Treatments of Obinutuzumab + Venetoclax Versus Obinutuzumab + Chlorambucil in Patients With Chronic Lymphocytic Leukemia

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ClinicalTrials.gov Identifier: NCT02242942

Recruitment Status : Active, not recruiting

First Posted : September 17, 2014

Results First Posted : October 1, 2019

Last Update Posted : March 12, 2024

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Sponsor:

Collaborators:

AbbVie

German CLL Study Group

Information provided by (Responsible Party):

Hoffmann-La Roche

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Lymphocytic Leukemia, Chronic
Interventions	Drug: Chlorambucil Drug: Venetoclax Drug: Obinutuzumab
Enrollment	445

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Obinutuzumab + Chlorambucil	Obinutuzumab + Venetoclax	Safety Run-in Obinutuzumab + Venetoclax
Arm/Group Description	Participants will receive obinutuzu...	Participants will receive obinutuzu...	Subjects received obinutuzumab for ...
Arm/Group Description	Participants will receive obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles will comprise 28 days.	Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.	Subjects received obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles comprised of 28 days.
Period Title: Overall Study
Started	216	216	13
Treated	214	212	13
Completed	0	0	0
Not Completed	216	216	13
Reason Not Completed
Death	17	20	2
Physician Decision	1	0	0
Withdrawal by Subject	8	10	0
On-going in Study	190	186	11

Baseline Characteristics

Arm/Group Title		Obinutuzumab + Chlorambucil	Obinutuzumab + Venetoclax	Safety Run-in Obinutuzumab + Venetoclax	Total
Arm/Group Description		Participants will receive obinutuzu...	Participants will receive obinutuzu...	Subjects received obinutuzumab for ...	Total of all reporting groups
Arm/Group Description		Participants will receive obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles will comprise 28 days.	Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.	Subjects received obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles comprised of 28 days.	Total of all reporting groups
Overall Number of Baseline Participants		216	216	13	445
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	216 participants	216 participants	13 participants	445 participants
		71.1 (8.0)	71.1 (8.2)	75.4 (7.8)	71.1 (8.1)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	216 participants	216 participants	13 participants	445 participants
	Female	73 33.8%	70 32.4%	5 38.5%	148 33.3%
	Male	143 66.2%	146 67.6%	8 61.5%	297 66.7%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	216 participants	216 participants	13 participants	445 participants
	Hispanic or Latino	20 9.3%	22 10.2%	1 7.7%	43 9.7%
	Not Hispanic or Latino	172 79.6%	165 76.4%	12 92.3%	349 78.4%
	Not Stated	19 8.8%	22 10.2%	0 0.0%	41 9.2%
	Unknown	5 2.3%	7 3.2%	0 0.0%	12 2.7%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	216 participants	216 participants	13 participants	445 participants
	American Indian or Alaska Native	1 0.5%	0 0.0%	0 0.0%	1 0.2%
	Black or African American	3 1.4%	1 0.5%	0 0.0%	4 0.9%
	Native Hawaiian or other Pacific Islande	0 0.0%	3 1.4%	0 0.0%	3 0.7%
	Unknown	18 8.3%	20 9.3%	0 0.0%	38 8.5%
	White	194 89.8%	192 88.9%	13 100.0%	399 89.7%

Outcome Measures

1.Primary Outcome


Title	Progression Free Survival (PFS) Based on Investigator Assessment According to IWCLL Criteria
Description	PFS was determined according to IWCLL 2008 criteria and defined as the...
Description	PFS was determined according to IWCLL 2008 criteria and defined as the time from randomization to the first occurrence of PD or death from any cause. Disease progression was characterized by at least one of the following: 1) >/= 50% increase in the absolute number of circulating lymphocytes to at least 5*10^9/L, 2) Appearance of new palpable lymph nodes (> 15 mm in longest diameter) or any new extra-nodal lesion; 3) >/= 50% increase in the longest diameter of any previous site of lymphadenopathy; 4) >/= 50% increase in the enlargement of the liver and/or spleen; 5) Transformation to a more aggressive histology.
Time Frame	Baseline until disease progression or death up to approximately 3.75 years

Outcome Measure Data

Analysis Population Description

ITT population was defined as all randomized participants.


Arm/Group Title	Obinutuzumab + Chlorambucil	Obinutuzumab + Venetoclax
Arm/Group Description:	Participants received obinutuzumab ...	Participants received obinutuzumab ...
Arm/Group Description:	Participants received obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles comprised 28 days.	Participants received obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles comprised 28 days.
Overall Number of Participants Analyzed	216	216
Median (95% Confidence Interval) Unit of Measure: months
	NA ^[1] (31.1 to NA)	NA ^[1] (NA to NA)

[1]

Insufficient number of participants with events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Obinutuzumab + Chlorambucil, Obinutuzumab + Venetoclax
	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	0.35
	Confidence Interval	(2-Sided) 95% 0.23 to 0.53
	Estimation Comments	Hazard Ratios were estimated by Cox regression model. Stratification factors: Binet and Geographic region.

2.Secondary Outcome


Title	Progression Free Survival (PFS) Based on Institutional Review Committee (IRC)-Assessments According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria
Description	PFS was determined according to IWCLL 2008 criteria and defined as the...
Description	PFS was determined according to IWCLL 2008 criteria and defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause. Disease progression was characterized by at least one of the following: 1) >/= 50% increase in the absolute number of circulating lymphocytes to at least 5*10^9/L, 2) Appearance of new palpable lymph nodes (> 15 mm in longest diameter) or any new extra-nodal lesion; 3) >/= 50% increase in the longest diameter of any previous site of lymphadenopathy; 4) >/= 50% increase in the enlargement of the liver and/or spleen; 5) Transformation to a more aggressive histology.
Time Frame	Baseline until disease progression or death up to approximately 3.75 years

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population was defined as all randomized participants.


Arm/Group Title	Obinutuzumab + Chlorambucil	Obinutuzumab + Venetoclax
Arm/Group Description:	Participants received obinutuzumab ...	Participants received obinutuzumab ...
Arm/Group Description:	Participants received obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles comprised 28 days.	Participants received obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles comprised 28 days.
Overall Number of Participants Analyzed	216	216
Median (95% Confidence Interval) Unit of Measure: months
	NA ^[1] (31.1 to NA)	NA ^[1] (NA to NA)

[1]

Insufficient number of participants with events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Obinutuzumab + Chlorambucil, Obinutuzumab + Venetoclax
	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	0.33
	Confidence Interval	(2-Sided) 95% 0.22 to 0.51
	Estimation Comments	Hazard ratios were estimated by Cox regression model. Stratification factors: Binet and Geographic region.

3.Secondary Outcome


Title	Percentage of Participants With an Overall Response (OR) at Completion of Treatment, as Determined by the Investigator According to IWCLL Criteria
Description	OR was defined as complete response (CR), CR with incomplete bone marr...
Description	OR was defined as complete response (CR), CR with incomplete bone marrow recovery (CRi), or partial response (PR) according to IWCLL 2008 criteria. CR requires all of the following: peripheral blood lymphocytes below 4x10^9/L, absence of lymphadenopathy by physical examination and computed tomography (CT) scan, no hepatomegaly or splenomegaly, absence of disease or constitutional symptoms, blood counts of neutrophils >1.510^9/L, platelets >10010^9/L and hemoglobin >110 g/L, bone marrow at least normocellular for age without clonal infiltrate (except for Cri). PR: two of the following features for at least 2 months: >/= 50% decrease in peripheral blood lymphocyte count from the pretreatment value, >/=50% reduction in lymphadenopathy, >/=50% reduction of liver and/or spleen enlargement, and at least one of the following blood counts: neutrophils >1.510^9/L, platelets >10010^9/L and hemoglobin >110 g/L.
Time Frame	At the completion of treatment assessment 3 months after treatment completion (at approximately 15 months)

Outcome Measure Data

Analysis Population Description

ITT population was defined as all randomized participants.


Arm/Group Title	Obinutuzumab + Chlorambucil	Obinutuzumab + Venetoclax
Arm/Group Description:	Participants received obinutuzumab ...	Participants received obinutuzumab ...
Arm/Group Description:	Participants received obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles comprised 28 days.	Participants received obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles comprised 28 days.
Overall Number of Participants Analyzed	216	216
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	71.3 (64.77 to 77.23)	84.7 (79.22 to 89.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Obinutuzumab + Chlorambucil, Obinutuzumab + Venetoclax
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0007
	Comments	P-value was assessed using Cochran-Mantel-Haenszel (CMH) test stratified by the IvRS randomization stratification factors.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	13.43
	Confidence Interval	(2-Sided) 95% 5.47 to 21.38
	Estimation Comments	95% Confidence Interval (CI) for difference in rates were constructed using Anderson-Hauck method.

4.Secondary Outcome


Title	Percentage of Participants With a Complete Response Rate (CRR) at the Completion of Treatment Assessment as Determined by the Investigator According to IWCLL Criteria
Description	CRR was defined as the rate of a clinical response of CR or CRi accord...
Description	CRR was defined as the rate of a clinical response of CR or CRi according to IWCLL 2008 criteria. CR requires all of the following: peripheral blood lymphocytes below 4x10^9/L, absence of lymphadenopathy by physical examination and CT scan, no hepatomegaly or splenomegaly, absence of disease or constitutional symptoms, blood counts of neutrophils >1.510^9/L, platelets >10010^9/L and hemoglobin >110 g/L, bone marrow at least normocellular for age without clonal infiltrate (except for Cri).
Time Frame	At the completion of treatment assessment 3 months after treatment completion (at approximately 15 months)

Outcome Measure Data

Analysis Population Description

ITT population was defined as all randomized participants.


Arm/Group Title	Obinutuzumab + Chlorambucil	Obinutuzumab + Venetoclax
Arm/Group Description:	Participants received obinutuzumab ...	Participants received obinutuzumab ...
Arm/Group Description:	Participants received obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles comprised 28 days.	Participants received obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles comprised 28 days.
Overall Number of Participants Analyzed	216	216
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	23.1 (17.70 to 29.35)	49.5 (42.68 to 56.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Obinutuzumab + Chlorambucil, Obinutuzumab + Venetoclax
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	P-value was assessed using CMH test stratified by the IvRS randomization stratification factors.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	26.39
	Confidence Interval	(2-Sided) 95% 17.41 to 35.36
	Estimation Comments	95% CI for difference in rates were constructed using Anderson-Hauck method.

5.Secondary Outcome


Title	Percentage of Participants With Minimal Residual Disease (MRD) Negativity in Peripheral Blood as Measured by Allele-Specific Oligonucleotide Polymerase Chain Reaction (ASO-PCR) at Completion of Treatment
Description	MRD negativity was defined as having < 1 CLL cell per 10,000 leucoc...
Description	MRD negativity was defined as having < 1 CLL cell per 10,000 leucocytes in peripheral blood.
Time Frame	At the completion of treatment assessment 3 months after treatment completion (at approximately 15 months)

Outcome Measure Data

Analysis Population Description

ITT population was defined as all randomized participants.


Arm/Group Title	Obinutuzumab + Chlorambucil	Obinutuzumab + Venetoclax
Arm/Group Description:	Participants will receive obinutuzu...	Participants will receive obinutuzu...
Arm/Group Description:	Participants will receive obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles will comprise 28 days.	Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.
Overall Number of Participants Analyzed	216	216
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	35.2 (28.83 to 41.95)	75.5 (69.17 to 81.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Obinutuzumab + Chlorambucil, Obinutuzumab + Venetoclax
	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	[Not Specified]

Method of Estimation	Estimation Parameter	Difference in MRD Negative Rates
	Estimated Value	40.28
	Confidence Interval	(2-Sided) 95% 31.45 to 49.10
	Estimation Comments	95% CI for difference in rates were constructed using Anderson-Hauck method.

6.Secondary Outcome


Title	Percentage of Participants With MRD Negativity in Bone Marrow as Measured by ASO-PCR at Completion of Treatment
Description	MRD negativity was defined as having < 1 CLL cell per 10,000 leucoc...
Description	MRD negativity was defined as having < 1 CLL cell per 10,000 leucocytes in bone marrow.
Time Frame	At the completion of treatment assessment 3 months after treatment completion (at approximately 15 months)

Outcome Measure Data

Analysis Population Description

ITT population was defined as all randomized participants.


Arm/Group Title	Obinutuzumab + Chlorambucil	Obinutuzumab + Venetoclax
Arm/Group Description:	Participants will receive obinutuzu...	Participants will receive obinutuzu...
Arm/Group Description:	Participants will receive obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles will comprise 28 days.	Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.
Overall Number of Participants Analyzed	216	216
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	17.1 (12.36 to 22.83)	56.9 (50.05 to 63.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Obinutuzumab + Chlorambucil, Obinutuzumab + Venetoclax
	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	[Not Specified]

Method of Estimation	Estimation Parameter	Difference in MRD Negative Rates
	Estimated Value	39.81
	Confidence Interval	(2-Sided) 95% 31.27 to 48.36
	Estimation Comments	95% CI for difference in rates were constructed using Anderson-Hauck method.

7.Secondary Outcome


Title	Overall Survival (OS)
Description	OS was defined as the time between the date of randomization and the d...
Description	OS was defined as the time between the date of randomization and the date of death due to any cause.
Time Frame	Baseline until death, up to approximately 10.75 years

Outcome Measure Data Not Reported

8.Secondary Outcome


Title	Percentage of Participants With MRD Negativity in Peripheral Blood as Measured by ASO-PCR at Completion of Combination Treatment Assessment
Description	MRD negativity was defined as having < 1 CLL cell per 10,000 leucoc...
Description	MRD negativity was defined as having < 1 CLL cell per 10,000 leucocytes in peripheral blood.
Time Frame	Day 1 Cycle 9 or 3 months after last IV infusion, approximately 9 months

Outcome Measure Data

Analysis Population Description

ITT population was defined as all randomized participants.


Arm/Group Title	Obinutuzumab + Chlorambucil	Obinutuzumab + Venetoclax
Arm/Group Description:	Participants will receive obinutuzu...	Participants will receive obinutuzu...
Arm/Group Description:	Participants will receive obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles will comprise 28 days.	Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.
Overall Number of Participants Analyzed	216	216
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	38.4 (31.91 to 45.27)	71.3 (64.77 to 77.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Obinutuzumab + Chlorambucil, Obinutuzumab + Venetoclax
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference in MRD Negative Rates
	Estimated Value	32.87
	Confidence Interval	(2-Sided) 95% 23.76 to 41.98
	Estimation Comments	95% CI for difference in rates were constructed using Anderson-Hauck method.

9.Secondary Outcome


Title	Percentage of Participants With MRD Negativity in Bone Marrow as Measured by ASO-PCR at Completion of Combination Treatment Assessment
Description	MRD negativity was defined as having < 1 CLL cell per 10,000 leucoc...
Description	MRD negativity was defined as having < 1 CLL cell per 10,000 leucocytes in bone marrow.
Time Frame	Day 1 Cycle 9 or 3 months after last IV infusion at approximately 9 months

Outcome Measure Data

Analysis Population Description

ITT population was defined as all randomized participants.


Arm/Group Title	Obinutuzumab + Chlorambucil	Obinutuzumab + Venetoclax
Arm/Group Description:	Participants will receive obinutuzu...	Participants will receive obinutuzu...
Arm/Group Description:	Participants will receive obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles will comprise 28 days.	Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.
Overall Number of Participants Analyzed	216	216
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	13.0 (8.79 to 18.19)	51.4 (44.51 to 58.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Obinutuzumab + Chlorambucil, Obinutuzumab + Venetoclax
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference in MRD Negative Rates
	Estimated Value	38.43
	Confidence Interval	(2-Sided) 95% 30.15 to 46.71
	Estimation Comments	95% CI for difference in rates were constructed using Anderson-Hauck method.

10.Secondary Outcome


Title	Percentage of Participants With OR at Completion of Combination Treatment Response Assessment
Description	OR was defined as CR, CRi or PR according to IWCLL 2008 criteria. CR r...
Description	OR was defined as CR, CRi or PR according to IWCLL 2008 criteria. CR required all of the following: peripheral blood lymphocytes below 4x10^9/L, absence of lymphadenopathy by physical examination, no hepatomegaly or splenomegaly, absence of disease or constitutional symptoms, blood counts of neutrophils >1.510^9/L, platelets >10010^9/L and hemoglobin >110 g/L. PR: two of the following features for at least 2 months: >/= 50% decrease in peripheral blood lymphocyte count from the pretreatment value, >/=50% reduction in lymphadenopathy, >/=50% reduction of liver and/or spleen enlargement, and at least one of the following blood counts: neutrophils >1.510^9/L, platelets >10010^9/L and hemoglobin >110 g/L.
Time Frame	Day 1 Cycle 7 or 28 days after last IV infusion, approximately 6 months

Outcome Measure Data

Analysis Population Description

ITT population was defined as all randomized participants.


Arm/Group Title	Obinutuzumab + Chlorambucil	Obinutuzumab + Venetoclax
Arm/Group Description:	Participants will receive obinutuzu...	Participants will receive obinutuzu...
Arm/Group Description:	Participants will receive obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles will comprise 28 days.	Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.
Overall Number of Participants Analyzed	216	216
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	86.6 (81.29 to 90.82)	88.4 (83.39 to 92.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Obinutuzumab + Chlorambucil, Obinutuzumab + Venetoclax
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.5612
	Comments	P-value was assessed using Cochran-Mantel-Haenszel (CMH) test stratified by the IvRS randomization stratification factors.
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	1.85
	Confidence Interval	(2-Sided) 95% -4.63 to 8.33
	Estimation Comments	95% Confidence Interval (CI) for difference in rates were constructed using Anderson-Hauck method.

11.Secondary Outcome


Title	Duration of Objective Response (DOR)
Description	PD was defined as lymphadenopathy, >=50% increase in liver or splee...
Description	PD was defined as lymphadenopathy, >=50% increase in liver or spleen size, >=50% increase in lymphocyte count, transformation to a more aggressive histology or occurrence of cytopenia.
Time Frame	Time from the first occurrence of a documented objective response to the time of PD as determined by the investigator or death from any cause, up to approximately 10.75 years

Outcome Measure Data Not Reported

12.Secondary Outcome


Title	Percentage of Participants By Best Response Achieved (CR, CRi, PR, Stable Disease (SD), or PD)
Description	CR: peripheral blood lymphocytes below 4x10^9/L, absence of lymphadeno...
Description	CR: peripheral blood lymphocytes below 4x10^9/L, absence of lymphadenopathy by physical examination and CT scan, no hepatomegaly or splenomegaly, absence of disease or constitutional symptoms, blood counts of neutrophils >1.510^9/L, platelets >10010^9/L and hemoglobin >110 g/L, bone marrow at least normocellular for age without clonal infiltrate (except for Cri). PR: any two for at least 2 months: >/= 50% decrease in peripheral blood lymphocyte count from the pretreatment value, >/=50% reduction in lymphadenopathy, >/=50% reduction of liver and/or spleen enlargement, and at least one of the following blood counts: neutrophils >1.510^9/L, platelets >10010^9/L and hemoglobin >110 g/L. PD: lymphadenopathy, >=50% increase in liver or spleen size, >=50% increase in lymphocyte count, transformation to a more aggressive histology or occurrence of cytopenia. SD: a non-response and used to characterize participants who did not achieve a CR or a PR, and who have not exhibited PD.
Time Frame	Baseline up to the completion of treatment assessment 3 months after treatment completion (up to approximately 15 months)

Outcome Measure Data

Analysis Population Description

ITT population was defined as all randomized participants.


Arm/Group Title	Obinutuzumab + Chlorambucil	Obinutuzumab + Venetoclax
Arm/Group Description:	Participants will receive obinutuzu...	Participants will receive obinutuzu...
Arm/Group Description:	Participants will receive obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles will comprise 28 days.	Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.
Overall Number of Participants Analyzed	216	216
Measure Type: Number Unit of Measure: percentage of participants
CR	56.0	70.4
CRi	5.6	7.9
PR	29.2	13.4
SD	1.9	0.5
PD	0.5	0.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Obinutuzumab + Chlorambucil, Obinutuzumab + Venetoclax
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.7169
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	P-value was assessed using CMH test stratified by the IvRS randomization stratification factors.

Method of Estimation	Estimation Parameter	Difference in Response Rates
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95% -4.66 to 6.51
	Estimation Comments	95% CI for difference in rates were constructed using Anderson-Hauck method.

13.Secondary Outcome


Title	Event-Free Survival
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Time between date of randomization and the date of disease progression/relapse on the basis of investigator-assessment, death, or start of a new anti-leukemic therapy, up to 10.75 years

Outcome Measure Data Not Reported

14.Secondary Outcome


Title	Time to Next Anti-Leukemic Treatment
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Time between the date of randomization and the date of first intake of new anti-leukemic therapy, up to 10.75 years

Outcome Measure Data Not Reported

15.Secondary Outcome


Title	Number of Participants With Adverse Events (AEs)
Description	An AE is any untoward medical occurrence in a participant administered...
Description	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs.
Time Frame	Up to approximately 10.75 years

Outcome Measure Data Not Reported

16.Secondary Outcome


Title	Percentage of Participants With CD19 + /CD5+ B Cells or CD14+ Monocytes
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline up to approximately 10.75 years

Outcome Measure Data Not Reported

17.Secondary Outcome


Title	Percentage of Participants With Human-Anti-Human Antibodies
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline up to approximately 10.75 years

Outcome Measure Data Not Reported

18.Secondary Outcome


Title	Percentage of Participants Recorded as Premature Study Withdrawals
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Up to approximately 10.75 years

Outcome Measure Data Not Reported

19.Secondary Outcome


Title	Plasma Concentrations of Venetoclax
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Pre-venetoclax dose (0 hour) and 4 hours post- venetoclax dose on Day 1 Cycle 4

Outcome Measure Data

Analysis Population Description

Analysis population consisted of subjects from whom one or more plasma samples were collected and who had received at least one 400 mg dose of venetoclax. Pre-dose and post-dose data may not come from the same participants. Total number analyzed is therefore higher than the number analyzed for each time point.


Arm/Group Title		Obinutuzumab + Venetoclax
Arm/Group Description:		Participants will receive obinutuzu...
Arm/Group Description:		Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.
Overall Number of Participants Analyzed		184
Mean (Standard Deviation) Unit of Measure: μg/mL
Pre-Dose	Number Analyzed	129 participants
Pre-Dose		0.578 (0.533)
4 hours Post-Dose	Number Analyzed	142 participants
4 hours Post-Dose		1.21 (0.765)

20.Secondary Outcome


Title	Serum Concentrations of Obinutuzumab
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Pre-obinutuzumab infusion (0 hour) and end of obinutuzumab infusion on Day 1 Cycle 4

Outcome Measure Data

Analysis Population Description

Analysis population consisted of subjects from whom one or more serum samples were collected and who had received at least one dose of obinutuzumab and one dose of 400 mg venetoclax. Pre-dose and post-dose data may not come from the same participants. Total number analyzed is therefore higher than the number analyzed for each time point.


Arm/Group Title		Obinutuzumab + Venetoclax
Arm/Group Description:		Participants will receive obinutuzu...
Arm/Group Description:		Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.
Overall Number of Participants Analyzed		184
Mean (Standard Deviation) Unit of Measure: μg/mL
Pre-Dose	Number Analyzed	133 participants
Pre-Dose		258 (140)
4 hours Post-Dose	Number Analyzed	133 participants
4 hours Post-Dose		568 (187)

21.Secondary Outcome


Title	Change From Baseline in M.D. Anderson Symptom Inventory-CLL (MDASI-CLL) Score
Description	The MDASI-CLL is a questionnaire of 25 items related to CLL specific s...
Description	The MDASI-CLL is a questionnaire of 25 items related to CLL specific symptoms that a participant may have experienced in the past 24 hours. Participants were asked to rate the severity of 13 symptoms called mean core symptom severity (i.e., pain, fatigue, nausea, disturbed sleep, distressed, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, sadness, vomiting, and numbness or tingling), 6 disease-specific symptoms called mean module symptom severity (night sweats, fevers and chills, lymph node swelling, diarrhea, easy bruising or bleeding, and constipation) and 6 mean interference on life questions (i.e., general activity, walking, work, mood, relations with other people, and enjoyment of life) on a scale from 0 to 10 with 0 indicating that the symptom is "not present" or "did not interfere" with the participant's activities and 10 indicating "as bad as you can imagine" or "interfered completely". Scores were averaged (range 0 to 10) for each of three parts.
Time Frame	Baseline up to approximately 10.75 years

Outcome Measure Data Not Reported

22.Secondary Outcome


Title	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQC30)
Description	The EORTC QLQ-C30 is a validated and reliable self-report measure cons...
Description	The EORTC QLQ-C30 is a validated and reliable self-report measure consisting of 30 questions incorporated into five functional scales (physical, role, cognitive, emotional, and social scales), three symptom scales (fatigue, pain, nausea, and vomiting scales), and a global health status/global quality-of-life scale. The remaining single items (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) assess the additional symptoms experienced by patients with cancer and the perceived financial burden of treatment. The 28 function and symptom items were scored on a 4-point scale that ranged from "not at all" to "very much," and the 2 global health status/global quality-of-life items were scored on a 7-point scale that ranged from "very poor" to "excellent." Raw average scale scores were linearly transformed to range 0-100 with higher scores indicating higher response levels (i.e., higher functioning, higher symptom severity).
Time Frame	Baseline up to approximately 10.75 years

Outcome Measure Data Not Reported

23.Secondary Outcome


Title	Change From Baseline in EuroQol 5 Dimension Questionnaire (EQ-5D-3L)
Description	The EQ-5D-3L questionnaire is a generic, preference based health utili...
Description	The EQ-5D-3L questionnaire is a generic, preference based health utility measure that assesses 5 health states (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and is used to build a composite of the patient's health status. The EQ-5D-3L was employed in this study to calculate health utilities for economic modeling, which ranged 0-1. The EQ-5D-3L also contained a visual analog scale (VAS) to assess the participant's overall health, which ranged from 0-100 with a higher score indicating a worse health status.
Time Frame	Baseline up to approximately 10.75 years

Outcome Measure Data Not Reported

Adverse Events

Time Frame	All AEs from first dose until 28 days after the last dose up to 1 year. Grade 3-4 AEs: for 6 months after last dose (up to 1.5 years). Major infections (Grade 3-4): for 2 years after the last dose (up to 3 years) irrespective of causality unless disease progressed and participant received leukemic treatment. Before disease progression, SAEs were reported during follow-up (up to 3.75 years). After disease progression, only related SAEs and second primary malignancies were reported.
Adverse Event Reporting Description	All-cause mortality was based on the ITT population defined as all randomized participants. Reporting of serious and non-serious adverse events was based on the safety population defined as all participants who received at least one dose of any study medication (i.e., obinutuzumab, venetoclax, or chlorambucil).

Arm/Group Title	Obinutuzumab + Chlorambucil		Obinutuzumab + Venetoclax		Safety Run-in Obinutuzumab + Venetoclax
Arm/Group Description	Participants will receive obinutuzu...		Participants will receive obinutuzu...		Subjects received obinutuzumab for ...
Arm/Group Description	Participants will receive obinutuzumab for 6 cycles and chlorambucil for 12 cycles. Cycles will comprise 28 days.		Participants will receive obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles will comprise 28 days.		Subjects received obinutuzumab for 6 cycles and venetoclax for 12 cycles. Cycles comprised of 28 days.
All-Cause Mortality
	Obinutuzumab + Chlorambucil		Obinutuzumab + Venetoclax		Safety Run-in Obinutuzumab + Venetoclax
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	17/216 (7.87%)		20/216 (9.26%)		2/13 (15.38%)
Serious Adverse Events Serious Adverse Events
	Obinutuzumab + Chlorambucil		Obinutuzumab + Venetoclax		Safety Run-in Obinutuzumab + Venetoclax
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	90/214 (42.06%)		104/212 (49.06%)		10/13 (76.92%)
Blood and lymphatic system disorders
Anaemia ^† 1	1/214 (0.47%)	1	2/212 (0.94%)	3	0/13 (0.00%)	0
Autoimmune haemolytic anaemia ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Coombs negative haemolytic anaemia ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Disseminated intravascular coagulation ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Febrile neutropenia ^† 1	8/214 (3.74%)	10	11/212 (5.19%)	12	3/13 (23.08%)	3
Immune thrombocytopenic purpura ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Neutropenia ^† 1	1/214 (0.47%)	1	3/212 (1.42%)	3	0/13 (0.00%)	0
Pancytopenia ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Splenic infarction ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Splenomegaly ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Thrombocytopenia ^† 1	5/214 (2.34%)	5	2/212 (0.94%)	2	1/13 (7.69%)	1
Cardiac disorders
Acute myocardial infarction ^† 1	0/214 (0.00%)	0	2/212 (0.94%)	2	0/13 (0.00%)	0
Atrial fibrillation ^† 1	3/214 (1.40%)	3	1/212 (0.47%)	1	0/13 (0.00%)	0
Atrial flutter ^† 1	2/214 (0.93%)	3	0/212 (0.00%)	0	0/13 (0.00%)	0
Bradycardia ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Cardiac arrest ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	1	0/13 (0.00%)	0
Cardiac failure ^† 1	1/214 (0.47%)	1	3/212 (1.42%)	3	0/13 (0.00%)	0
Mitral valve incompetence ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Myocardial infarction ^† 1	3/214 (1.40%)	4	1/212 (0.47%)	1	1/13 (7.69%)	1
Myocardial ischaemia ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Supraventricular tachycardia ^† 1	2/214 (0.93%)	2	0/212 (0.00%)	0	0/13 (0.00%)	0
Tachycardia ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Ventricular fibrillation ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Congenital, familial and genetic disorders
Gilbert's syndrome ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Ear and labyrinth disorders
Vertigo ^† 1	0/214 (0.00%)	0	2/212 (0.94%)	2	0/13 (0.00%)	0
Eye disorders
Amaurosis fugax ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Eye inflammation ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Keratitis ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Gastrointestinal disorders
Colitis ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Diarrhoea ^† 1	0/214 (0.00%)	0	2/212 (0.94%)	2	1/13 (7.69%)	1
Duodenal ulcer haemorrhage ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Enteritis ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Faecaloma ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Gastric ulcer perforation ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Inguinal hernia ^† 1	1/214 (0.47%)	2	2/212 (0.94%)	2	0/13 (0.00%)	0
Large intestine polyp ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Upper gastrointestinal haemorrhage ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
General disorders
Adverse drug reaction ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Asthenia ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Chest pain ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Chills ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Device related thrombosis ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	1	0/13 (0.00%)	0
Fatigue ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	1	0/13 (0.00%)	0
General physical health deterioration ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	1/13 (7.69%)	1
Pyrexia ^† 1	7/214 (3.27%)	8	8/212 (3.77%)	8	2/13 (15.38%)	2
Hepatobiliary disorders
Cholecystitis acute ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Cholelithiasis ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Immune system disorders
Anaphylactic reaction ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Infections and infestations
Atypical pneumonia ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	1	0/13 (0.00%)	0
Bronchiolitis ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Bronchitis ^† 1	2/214 (0.93%)	2	2/212 (0.94%)	2	0/13 (0.00%)	0
Bronchopulmonary aspergillosis ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Candida infection ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Cellulitis ^† 1	0/214 (0.00%)	0	3/212 (1.42%)	3	0/13 (0.00%)	0
Cholecystitis infective ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Chronic sinusitis ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Cytomegalovirus infection ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Device related infection ^† 1	0/214 (0.00%)	0	2/212 (0.94%)	2	0/13 (0.00%)	0
Eczema infected ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Endocarditis ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	2	0/13 (0.00%)	0
Erysipelas ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Gastroenteritis ^† 1	2/214 (0.93%)	2	0/212 (0.00%)	0	0/13 (0.00%)	0
Gastroenteritis viral ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Gastrointestinal infection ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Hepatitis E ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Herpes zoster ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Infection ^† 1	2/214 (0.93%)	2	2/212 (0.94%)	4	0/13 (0.00%)	0
Infectious pleural effusion ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	1	0/13 (0.00%)	0
Infective exacerbation of chronic obstructive airways disease ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Influenza ^† 1	2/214 (0.93%)	2	1/212 (0.47%)	1	1/13 (7.69%)	1
Listeriosis ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Lower respiratory tract infection ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Lung infection ^† 1	2/214 (0.93%)	2	0/212 (0.00%)	0	0/13 (0.00%)	0
Muscle abscess ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Neutropenic infection ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Ophthalmic herpes zoster ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Pneumocystis jirovecii pneumonia ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	1	1/13 (7.69%)	1
Pneumonia ^† 1	9/214 (4.21%)	11	10/212 (4.72%)	10	1/13 (7.69%)	1
Pneumonia fungal ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Pneumonia haemophilus ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Pneumonia respiratory syncytial viral ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Pseudomembranous colitis ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Pyelonephritis ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	1	0/13 (0.00%)	0
Respiratory tract infection ^† 1	1/214 (0.47%)	1	2/212 (0.94%)	2	0/13 (0.00%)	0
Sepsis ^† 1	2/214 (0.93%)	2	6/212 (2.83%)	7	1/13 (7.69%)	2
Septic shock ^† 1	2/214 (0.93%)	2	1/212 (0.47%)	1	1/13 (7.69%)	1
Sinusitis aspergillus ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Soft tissue infection ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Staphylococcal infection ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Urinary tract infection ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	1	0/13 (0.00%)	0
Urosepsis ^† 1	1/214 (0.47%)	2	2/212 (0.94%)	2	0/13 (0.00%)	0
Varicella zoster virus infection ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Wound infection fungal ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Injury, poisoning and procedural complications
Chillblains ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Clavicle fracture ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Femoral neck fracture ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Femur fracture ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Head injury ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Infusion related reaction ^† 1	13/214 (6.07%)	13	9/212 (4.25%)	9	1/13 (7.69%)	1
Limb injury ^† 1	2/214 (0.93%)	2	0/212 (0.00%)	0	0/13 (0.00%)	0
Lumbar vertebral fracture ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Overdose ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Pelvic fracture ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Rib fracture ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Subcutaneous haematoma ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Subdural haematoma ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Thoracic vertebral fracture ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Toxicity to various agents ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Transfusion reaction ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Traumatic haemothorax ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Vasoplegia syndrome ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Wound evisceration ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Investigations
Alanine aminotransferase increased ^† 1	3/214 (1.40%)	3	0/212 (0.00%)	0	0/13 (0.00%)	0
Aspartate aminotransferase increased ^† 1	4/214 (1.87%)	4	0/212 (0.00%)	0	0/13 (0.00%)	0
Blood urea increased ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Hepatic enzyme increased ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Prothrombin time prolonged ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Transaminases increased ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	1/13 (7.69%)	1
White blood cell count decreased ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Dehydration ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Hypercalcaemia ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Hyperglycaemia ^† 1	2/214 (0.93%)	2	1/212 (0.47%)	1	0/13 (0.00%)	0
Hyperkalaemia ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Hypoglycaemia ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Hyponatraemia ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	1	0/13 (0.00%)	0
Tumour lysis syndrome ^† 1	4/214 (1.87%)	4	1/212 (0.47%)	1	0/13 (0.00%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion ^† 1	2/214 (0.93%)	2	0/212 (0.00%)	0	0/13 (0.00%)	0
Lumbar spinal stenosis ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Musculoskeletal pain ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Spondylitis ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Anal squamous cell carcinoma ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Basal cell carcinoma ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Bladder cancer ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Bladder cancer recurrent ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Bladder neoplasm ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Invasive breast carcinoma ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Invasive ductal breast carcinoma ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Lung adenocarcinoma ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Lung adenocarcinoma stage IV ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Malignant melanoma ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	1	0/13 (0.00%)	0
Metastatic malignant melanoma ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Myelodysplastic syndrome ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Pancreatic carcinoma metastatic ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Penile cancer ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Prostate cancer ^† 1	0/214 (0.00%)	0	2/212 (0.94%)	2	0/13 (0.00%)	0
Prostate cancer metastatic ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Salivary gland adenoma ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Sarcoma of skin ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Skin squamous cell carcinoma metastatic ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Squamous cell carcinoma of skin ^† 1	3/214 (1.40%)	3	2/212 (0.94%)	2	0/13 (0.00%)	0
T-cell lymphoma ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Nervous system disorders
Cerebral haemorrhage ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Cerebral infarction ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Cerebral ischaemia ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Cerebrovascular accident ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Generalised tonic-clonic seizure ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Headache ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Ischaemic stroke ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Presyncope ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	1/13 (7.69%)	1
Radiculopathy ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Seizure ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Syncope ^† 1	2/214 (0.93%)	2	1/212 (0.47%)	1	0/13 (0.00%)	0
Transient ischaemic attack ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	2	1/13 (7.69%)	1
Vertebrobasilar insufficiency ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Psychiatric disorders
Confusional state ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Delirium ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Depression ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Renal and urinary disorders
Nephrolithiasis ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Reproductive system and breast disorders
Cystocele ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Bronchitis chronic ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Bronchopneumopathy ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Bronchospasm ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Chronic obstructive pulmonary disease ^† 1	2/214 (0.93%)	2	3/212 (1.42%)	10	0/13 (0.00%)	0
Cough ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	1	0/13 (0.00%)	0
Dyspnoea ^† 1	0/214 (0.00%)	0	2/212 (0.94%)	2	0/13 (0.00%)	0
Hypoxia ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Lung disorder ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	1	0/13 (0.00%)	0
Pleural effusion ^† 1	2/214 (0.93%)	3	1/212 (0.47%)	1	0/13 (0.00%)	0
Pneumonia aspiration ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Pneumonitis ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Pulmonary embolism ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Pulmonary oedema ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Skin and subcutaneous tissue disorders
Blister ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Diabetic foot ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Rash ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Urticaria ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Surgical and medical procedures
Aortic valve replacement ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Medical device removal ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Vascular disorders
Aortic stenosis ^† 1	0/214 (0.00%)	0	2/212 (0.94%)	2	0/13 (0.00%)	0
Deep vein thrombosis ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Hypertension ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
Hypotension ^† 1	2/214 (0.93%)	2	0/212 (0.00%)	0	0/13 (0.00%)	0
Peripheral arterial occlusive disease ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	0/13 (0.00%)	0
Thrombophlebitis superficial ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	0/13 (0.00%)	0
1 Term from vocabulary, MedDRA, version 21.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Obinutuzumab + Chlorambucil		Obinutuzumab + Venetoclax		Safety Run-in Obinutuzumab + Venetoclax
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	205/214 (95.79%)		193/212 (91.04%)		12/13 (92.31%)
Blood and lymphatic system disorders
Anaemia ^† 1	39/214 (18.22%)	55	33/212 (15.57%)	53	2/13 (15.38%)	2
Leukopenia ^† 1	13/214 (6.07%)	19	12/212 (5.66%)	23	1/13 (7.69%)	1
Neutropenia ^† 1	122/214 (57.01%)	294	121/212 (57.08%)	370	8/13 (61.54%)	12
Thrombocytopenia ^† 1	49/214 (22.90%)	76	49/212 (23.11%)	86	2/13 (15.38%)	5
Cardiac disorders
Coronary artery disease ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Tachycardia ^† 1	1/214 (0.47%)	1	5/212 (2.36%)	5	1/13 (7.69%)	1
Ventricular extrasystoles ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	1	1/13 (7.69%)	1
Ear and labyrinth disorders
Excessive cerumen production ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	1/13 (7.69%)	1
Gastrointestinal disorders
Abdominal pain ^† 1	10/214 (4.67%)	11	11/212 (5.19%)	15	2/13 (15.38%)	2
Abdominal pain upper ^† 1	4/214 (1.87%)	4	7/212 (3.30%)	7	1/13 (7.69%)	1
Constipation ^† 1	19/214 (8.88%)	23	28/212 (13.21%)	32	5/13 (38.46%)	6
Diarrhoea ^† 1	32/214 (14.95%)	42	59/212 (27.83%)	99	5/13 (38.46%)	8
Dry mouth ^† 1	4/214 (1.87%)	4	0/212 (0.00%)	0	1/13 (7.69%)	1
Dyspepsia ^† 1	3/214 (1.40%)	3	7/212 (3.30%)	7	1/13 (7.69%)	1
Epigastric discomfort ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Haemorrhoids ^† 1	0/214 (0.00%)	0	2/212 (0.94%)	2	1/13 (7.69%)	1
Nausea ^† 1	46/214 (21.50%)	62	40/212 (18.87%)	61	4/13 (30.77%)	7
Stomatitis ^† 1	2/214 (0.93%)	2	1/212 (0.47%)	1	1/13 (7.69%)	2
Vomiting ^† 1	18/214 (8.41%)	22	21/212 (9.91%)	27	3/13 (23.08%)	3
General disorders
Adverse drug reaction ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Asthenia ^† 1	17/214 (7.94%)	20	14/212 (6.60%)	20	0/13 (0.00%)	0
Chills ^† 1	10/214 (4.67%)	13	12/212 (5.66%)	14	1/13 (7.69%)	1
Extravasation ^† 1	2/214 (0.93%)	2	0/212 (0.00%)	0	1/13 (7.69%)	1
Fatigue ^† 1	29/214 (13.55%)	36	32/212 (15.09%)	40	3/13 (23.08%)	6
Influenza like illness ^† 1	3/214 (1.40%)	3	4/212 (1.89%)	4	1/13 (7.69%)	1
Oedema ^† 1	7/214 (3.27%)	7	3/212 (1.42%)	3	1/13 (7.69%)	1
Oedema peripheral ^† 1	16/214 (7.48%)	18	17/212 (8.02%)	20	1/13 (7.69%)	2
Pyrexia ^† 1	26/214 (12.15%)	28	40/212 (18.87%)	53	3/13 (23.08%)	4
Sensation of foreign body ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Infections and infestations
Bronchitis ^† 1	5/214 (2.34%)	6	11/212 (5.19%)	14	1/13 (7.69%)	2
Cystitis ^† 1	2/214 (0.93%)	2	1/212 (0.47%)	1	1/13 (7.69%)	1
Ear infection ^† 1	0/214 (0.00%)	0	2/212 (0.94%)	2	1/13 (7.69%)	1
Eye infection ^† 1	1/214 (0.47%)	1	0/212 (0.00%)	0	1/13 (7.69%)	3
Herpes zoster ^† 1	6/214 (2.80%)	7	9/212 (4.25%)	9	1/13 (7.69%)	1
Influenza ^† 1	4/214 (1.87%)	4	3/212 (1.42%)	3	1/13 (7.69%)	1
Localised infection ^† 1	3/214 (1.40%)	3	1/212 (0.47%)	1	1/13 (7.69%)	1
Nasopharyngitis ^† 1	14/214 (6.54%)	16	16/212 (7.55%)	16	0/13 (0.00%)	0
Oral herpes ^† 1	4/214 (1.87%)	5	5/212 (2.36%)	7	1/13 (7.69%)	4
Paronychia ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Pneumonia ^† 1	3/214 (1.40%)	3	6/212 (2.83%)	9	1/13 (7.69%)	1
Respiratory tract infection ^† 1	6/214 (2.80%)	7	10/212 (4.72%)	14	1/13 (7.69%)	3
Rhinitis ^† 1	5/214 (2.34%)	6	2/212 (0.94%)	3	1/13 (7.69%)	1
Sinusitis ^† 1	6/214 (2.80%)	6	8/212 (3.77%)	8	1/13 (7.69%)	1
Upper respiratory tract infection ^† 1	15/214 (7.01%)	17	16/212 (7.55%)	19	2/13 (15.38%)	4
Urinary tract infection ^† 1	9/214 (4.21%)	10	10/212 (4.72%)	13	1/13 (7.69%)	1
Viral skin infection ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Injury, poisoning and procedural complications
Arthropod bite ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	1/13 (7.69%)	1
Eye contusion ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	1/13 (7.69%)	1
Fall ^† 1	8/214 (3.74%)	11	5/212 (2.36%)	7	1/13 (7.69%)	1
Head injury ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Infusion related reaction ^† 1	103/214 (48.13%)	131	89/212 (41.98%)	122	9/13 (69.23%)	10
Limb injury ^† 1	4/214 (1.87%)	4	0/212 (0.00%)	0	1/13 (7.69%)	1
Skin abrasion ^† 1	0/214 (0.00%)	0	2/212 (0.94%)	2	1/13 (7.69%)	1
Investigations
Alanine aminotransferase increased ^† 1	13/214 (6.07%)	15	11/212 (5.19%)	15	0/13 (0.00%)	0
Aspartate aminotransferase increased ^† 1	17/214 (7.94%)	20	12/212 (5.66%)	14	0/13 (0.00%)	0
Blood albumin decreased ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Blood creatinine increased ^† 1	6/214 (2.80%)	6	7/212 (3.30%)	9	1/13 (7.69%)	2
Blood glucose increased ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	1	1/13 (7.69%)	1
Blood lactate dehydrogenase increased ^† 1	2/214 (0.93%)	2	2/212 (0.94%)	2	2/13 (15.38%)	2
Blood magnesium decreased ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	1/13 (7.69%)	1
Blood phosphorus increased ^† 1	1/214 (0.47%)	1	2/212 (0.94%)	4	1/13 (7.69%)	1
C-reactive protein increased ^† 1	2/214 (0.93%)	2	4/212 (1.89%)	4	1/13 (7.69%)	1
Neutrophil count decreased ^† 1	11/214 (5.14%)	32	10/212 (4.72%)	27	0/13 (0.00%)	0
Procalcitonin increased ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Protein total decreased ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Transaminases increased ^† 1	2/214 (0.93%)	2	0/212 (0.00%)	0	1/13 (7.69%)	1
Weight decreased ^† 1	5/214 (2.34%)	5	5/212 (2.36%)	5	1/13 (7.69%)	1
Metabolism and nutrition disorders
Decreased appetite ^† 1	6/214 (2.80%)	8	10/212 (4.72%)	10	1/13 (7.69%)	1
Gout ^† 1	1/214 (0.47%)	2	3/212 (1.42%)	4	1/13 (7.69%)	1
Hyperglycaemia ^† 1	7/214 (3.27%)	7	14/212 (6.60%)	16	2/13 (15.38%)	4
Hyperkalaemia ^† 1	5/214 (2.34%)	6	4/212 (1.89%)	13	5/13 (38.46%)	7
Hyperphosphataemia ^† 1	3/214 (1.40%)	3	4/212 (1.89%)	5	1/13 (7.69%)	1
Tumour lysis syndrome ^† 1	1/214 (0.47%)	1	2/212 (0.94%)	2	2/13 (15.38%)	2
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	18/214 (8.41%)	23	16/212 (7.55%)	19	1/13 (7.69%)	1
Back pain ^† 1	20/214 (9.35%)	21	21/212 (9.91%)	24	2/13 (15.38%)	2
Groin pain ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Intervertebral disc protrusion ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Muscle spasms ^† 1	11/214 (5.14%)	11	10/212 (4.72%)	11	1/13 (7.69%)	1
Musculoskeletal chest pain ^† 1	0/214 (0.00%)	0	2/212 (0.94%)	4	2/13 (15.38%)	2
Musculoskeletal pain ^† 1	4/214 (1.87%)	4	7/212 (3.30%)	8	1/13 (7.69%)	2
Pain in extremity ^† 1	13/214 (6.07%)	14	10/212 (4.72%)	11	1/13 (7.69%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma ^† 1	5/214 (2.34%)	6	6/212 (2.83%)	6	1/13 (7.69%)	1
Benign breast neoplasm ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Seborrhoeic keratosis ^† 1	0/214 (0.00%)	0	2/212 (0.94%)	2	1/13 (7.69%)	1
Skin papilloma ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	1/13 (7.69%)	1
Nervous system disorders
Dizziness ^† 1	17/214 (7.94%)	20	16/212 (7.55%)	18	4/13 (30.77%)	5
Headache ^† 1	21/214 (9.81%)	24	23/212 (10.85%)	29	3/13 (23.08%)	3
Paraesthesia ^† 1	1/214 (0.47%)	1	4/212 (1.89%)	4	1/13 (7.69%)	1
Presyncope ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	1	2/13 (15.38%)	3
Somnolence ^† 1	0/214 (0.00%)	0	1/212 (0.47%)	1	1/13 (7.69%)	1
Syncope ^† 1	4/214 (1.87%)	4	5/212 (2.36%)	5	2/13 (15.38%)	2
Tremor ^† 1	3/214 (1.40%)	4	6/212 (2.83%)	6	1/13 (7.69%)	1
Psychiatric disorders
Depression ^† 1	1/214 (0.47%)	1	8/212 (3.77%)	8	1/13 (7.69%)	1
Renal and urinary disorders
Dysuria ^† 1	2/214 (0.93%)	2	1/212 (0.47%)	1	1/13 (7.69%)	1
Renal failure ^† 1	1/214 (0.47%)	1	1/212 (0.47%)	1	1/13 (7.69%)	3
Renal impairment ^† 1	0/214 (0.00%)	0	2/212 (0.94%)	2	1/13 (7.69%)	1
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	24/214 (11.21%)	27	33/212 (15.57%)	37	6/13 (46.15%)	6
Dyspnoea ^† 1	11/214 (5.14%)	12	11/212 (5.19%)	12	1/13 (7.69%)	2
Epistaxis ^† 1	4/214 (1.87%)	5	3/212 (1.42%)	3	1/13 (7.69%)	1
Pharyngeal paraesthesia ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Productive cough ^† 1	3/214 (1.40%)	3	6/212 (2.83%)	6	1/13 (7.69%)	2
Rhinorrhoea ^† 1	3/214 (1.40%)	3	3/212 (1.42%)	3	1/13 (7.69%)	1
Throat irritation ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
Skin and subcutaneous tissue disorders
Dry skin ^† 1	6/214 (2.80%)	7	4/212 (1.89%)	4	2/13 (15.38%)	2
Erythema ^† 1	4/214 (1.87%)	4	2/212 (0.94%)	2	2/13 (15.38%)	2
Pruritus ^† 1	9/214 (4.21%)	9	18/212 (8.49%)	20	6/13 (46.15%)	6
Rash ^† 1	12/214 (5.61%)	13	12/212 (5.66%)	12	2/13 (15.38%)	3
Urticaria ^† 1	5/214 (2.34%)	5	0/212 (0.00%)	0	1/13 (7.69%)	1
Vascular disorders
Flushing ^† 1	3/214 (1.40%)	3	2/212 (0.94%)	2	2/13 (15.38%)	2
Hypertension ^† 1	11/214 (5.14%)	12	12/212 (5.66%)	17	0/13 (0.00%)	0
Hypotension ^† 1	8/214 (3.74%)	10	11/212 (5.19%)	15	2/13 (15.38%)	2
Thrombophlebitis ^† 1	0/214 (0.00%)	0	0/212 (0.00%)	0	1/13 (7.69%)	1
1 Term from vocabulary, MedDRA, version 21.0 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Medical Communications
Organization:	Hoffmann-La Roche
Phone:	800 821-8590
EMail:	genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Badawi M, Chen X, Marroum P, Suleiman AA, Mensing S, Koenigsdorfer A, Schiele JT, Palenski T, Samineni D, Hoffman D, Menon R, Salem AH. Bioavailability Evaluation of Venetoclax Lower-Strength Tablets and Oral Powder Formulations to Establish Interchangeability with the 100 mg Tablet. Clin Drug Investig. 2022 Aug;42(8):657-668. doi: 10.1007/s40261-022-01172-4. Epub 2022 Jul 13.

Samineni D, Gibiansky L, Wang B, Vadhavkar S, Rajwanshi R, Tandon M, Sinha A, Al-Sawaf O, Fischer K, Hallek M, Salem AH, Li C, Miles D. Pharmacokinetics and Exposure-Response Analysis of Venetoclax + Obinutuzumab in Chronic Lymphocytic Leukemia: Phase 1b Study and Phase 3 CLL14 Trial. Adv Ther. 2022 Aug;39(8):3635-3653. doi: 10.1007/s12325-022-02170-w. Epub 2022 Jun 16.

Al-Sawaf O, Zhang C, Lu T, Liao MZ, Panchal A, Robrecht S, Ching T, Tandon M, Fink AM, Tausch E, Schneider C, Ritgen M, Bottcher S, Kreuzer KA, Chyla B, Miles D, Wendtner CM, Eichhorst B, Stilgenbauer S, Jiang Y, Hallek M, Fischer K. Minimal Residual Disease Dynamics after Venetoclax-Obinutuzumab Treatment: Extended Off-Treatment Follow-up From the Randomized CLL14 Study. J Clin Oncol. 2021 Dec 20;39(36):4049-4060. doi: 10.1200/JCO.21.01181. Epub 2021 Oct 28.

Al-Sawaf O, Zhang C, Tandon M, Sinha A, Fink AM, Robrecht S, Samoylova O, Liberati AM, Pinilla-Ibarz J, Opat S, Sivcheva L, Le Du K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S, Kipps TJ, Tausch E, Schary W, Ritgen M, Wendtner CM, Kreuzer KA, Eichhorst B, Stilgenbauer S, Hallek M, Fischer K. Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1188-1200. doi: 10.1016/S1470-2045(20)30443-5.

Fischer K, Al-Sawaf O, Bahlo J, Fink AM, Tandon M, Dixon M, Robrecht S, Warburton S, Humphrey K, Samoylova O, Liberati AM, Pinilla-Ibarz J, Opat S, Sivcheva L, Le Du K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S, Kipps TJ, Boettcher S, Tausch E, Humerickhouse R, Eichhorst B, Wendtner CM, Langerak AW, Kreuzer KA, Ritgen M, Goede V, Stilgenbauer S, Mobasher M, Hallek M. Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. N Engl J Med. 2019 Jun 6;380(23):2225-2236. doi: 10.1056/NEJMoa1815281. Epub 2019 Jun 4.

Layout table for additonal information

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT02242942
Other Study ID Numbers:	BO25323 2014-001810-24 ( EudraCT Number ) CLL14
First Submitted:	September 16, 2014
First Posted:	September 17, 2014
Results First Submitted:	August 15, 2019
Results First Posted:	October 1, 2019
Last Update Posted:	March 12, 2024

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