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Clinical Trial Results:
A Phase II, Open-Label Study Evaluating the Safety and Efficacy of GDC-0199 (ABT-199) Plus Bendamustine Plus Rituximab (BR) in Comparison with BR Alone or GDC-0199 Plus Rituximab (R) in Patients with Relapsed and Refractory Follicular Non-Hodgkin’s Lymphoma

Summary
EudraCT number	2014-000576-26
Trial protocol	GB IT DE BE FR
Global end of trial date	16 Mar 2018

Results information
Results version number	v3(current)
This version publication date	23 Mar 2019
First version publication date	14 Oct 2017
Other versions	v1 , v2
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

BO29337

ISRCTN number

US NCT number

NCT02187861

WHO universal trial number (UTN)

Sponsor organisation name

Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4070

Public contact

Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com

Scientific contact

Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

16 Mar 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

16 Mar 2018

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy of venetoclax plus BR compared with BR alone and venetoclax plus rituximab in participants with relapsed and refractory follicular lymphoma, as measured by the positron emission tomography (PET) defined complete metabolic response (CMR) at the time of primary response assessment as defined by an Independent Review Committee (IRC)

Protection of trial subjects

The study was conducted in accordance with the principles of the “Declaration of Helsinki” and Good Clinical Practice (GCP) according to the applicable local regulations and policies.

Background therapy

Evidence for comparator

Actual start date of recruitment

13 Nov 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 33

Country: Number of subjects enrolled

Belgium: 4

Country: Number of subjects enrolled

Canada: 22

Country: Number of subjects enrolled

France: 13

Country: Number of subjects enrolled

United Kingdom: 18

Country: Number of subjects enrolled

Germany: 17

Country: Number of subjects enrolled

Italy: 23

Country: Number of subjects enrolled

United States: 33

Worldwide total number of subjects

163

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

The date of first patient first visit was 13 November 2014 and the date of last patient last visit (LPLV) was 16 March 2018.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)

Arm description

Participants received venetoclax no more than 600 milligrams (mg) orally once daily continuously along with rituximab 375 milligrams per square meter (mg/m^2) intravenous (IV) infusion on Day 1 of 28-day cycle and bendamustine 90 mg/m^2 IV infusion on Days 1 and 2 of the 28-day cycle. Safety run-in continued until first 9 participants completed the safety observation window of 28 days. After first 28 days of safety observation (Cycle 1), participants continued to receive venetoclax 600 mg orally once daily up to 1 year along with rituximab 375 mg/m^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.

Arm type

Experimental

Investigational medicinal product name

Venetoclax

Investigational medicinal product code

GDC-0199

Other name

ABT-199

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Venetoclax was administered as per the schedule specified under arm description.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

MabThera, Rituxan

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab was administered as per the schedule specified under arm description.

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Levact

Pharmaceutical forms

Powder for concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bendamustine was administered as per the schedule specified under arm description.

Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)

Arm description

Participants received venetoclax 800 mg orally once daily for 1 year along with rituximab 375 mg/m^2 IV infusion on Days 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycles 4, 6, 8, 10, and 12. Each cycle was of 28 days.

Arm type

Experimental

Investigational medicinal product name

Venetoclax

Investigational medicinal product code

GDC-0199

Other name

ABT-199

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Venetoclax was administered as per the schedule specified under arm description.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

MabThera, Rituxan

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab was administered as per the schedule specified under arm description.

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)

Arm description

Participants received venetoclax 800 mg orally once daily continuously for 1 year along with rituximab 375 mg/m^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.

Arm type

Experimental

Investigational medicinal product name

Venetoclax

Investigational medicinal product code

GDC-0199

Other name

ABT-199

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Venetoclax was administered as per the schedule specified under arm description.

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Levact

Pharmaceutical forms

Powder for concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bendamustine was administered as per the schedule specified under arm description.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

MabThera, Rituxan

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab was administered as per the schedule specified under arm description.

Chemotherapy-Containing Cohort: Arm C (BR)

Arm description

Participants received rituximab 375 mg/m^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.

Arm type

Active comparator

Investigational medicinal product name

Bendamustine

Investigational medicinal product code

Other name

Levact

Pharmaceutical forms

Powder for concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Bendamustine was administered as per the schedule specified under arm description.

Investigational medicinal product name

Rituximab

Investigational medicinal product code

Other name

MabThera, Rituxan

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Rituximab was administered as per the schedule specified under arm description.

Number of subjects in period 1	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Started	9	52	51	51
Treated	9	52	49	50
Completed	3	4	19	19
Not completed	6	48	32	32
Adverse event, serious fatal	-	3	1	2
Physician decision	-	1	-	3
Consent withdrawn by subject	-	-	3	3
Adverse event, non-fatal	2	1	2	1
Progressive Disease	4	42	19	22
Unspecified	-	1	7	1

Baseline characteristics

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Reporting group title

Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)

Reporting group description

Reporting group title

Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)

Reporting group description

Reporting group title

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)

Reporting group description

Reporting group title

Chemotherapy-Containing Cohort: Arm C (BR)

Reporting group description

Participants received rituximab 375 mg/m^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.

Reporting group values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)	Total
Number of subjects	9	52	51	51	163
Age categorical
Units: Subjects
In utero					0
Preterm newborn infants (gestational age < 37 wks)					0
Newborns (0-27 days)					0
Infants and toddlers (28 days-23 months)					0
Children (2-11 years)					0
Adolescents (12-17 years)					0
Adults (18-64 years)					0
From 65-84 years					0
85 years and over					0
Age Continuous
Units: years
arithmetic mean (standard deviation)	57.9 ( 12.7 )	61.9 ( 12.0 )	64.9 ( 9.8 )	61.0 ( 11.6 )	-
Gender, Male/Female
Units: Subjects
Female	5	25	16	21	67
Male	4	27	35	30	96

End points

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Reporting group title

Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)

Reporting group description

Reporting group title

Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)

Reporting group description

Reporting group title

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)

Reporting group description

Reporting group title

Chemotherapy-Containing Cohort: Arm C (BR)

Reporting group description

Participants received rituximab 375 mg/m^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.

Primary: Percentage of Participants with Complete Metabolic Response (CMR) According to Independent Review Committee (IRC) as per Lugano Classification, Using Positron Emission Tomography (PET) Scan at Primary Response Assessment (PRA)

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End point title

Percentage of Participants with Complete Metabolic Response (CMR) According to Independent Review Committee (IRC) as per Lugano Classification, Using Positron Emission Tomography (PET) Scan at Primary Response Assessment (PRA)

End point description

CMR: a score 1 (no uptake above background), 2 (uptake less than or equal to [<=] mediastinum), or 3 (uptake less than [<] mediastinum but <=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites with no new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Assessment was performed by an IRC according to Lugano classification using PET scan. 95% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method.

End point type

Primary

End point timeframe

6-8 weeks after Cycle 6 Day 1 (PRA) (Cycle length = 28 days)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: percentage of participants
number (confidence interval 95%)	55.6 (21.20 to 86.30)	11.5 (4.35 to 23.44)	74.5 (60.37 to 85.67)	70.6 (56.17 to 82.51)

Statistical Analysis 1

Comparison groups

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) v Chemotherapy-Containing Cohort: Arm C (BR)

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference in response rates

Point estimate

3.92

Confidence interval

level

95%

sides

2-sided

lower limit

-13.38

upper limit

21.23

Secondary: Percentage of Participants with CMR According to Investigator as per Lugano Classification, Using PET Scan at PRA

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End point title

Percentage of Participants with CMR According to Investigator as per Lugano Classification, Using PET Scan at PRA

End point description

CMR: a score 1 (no uptake above background), 2 (uptake <=mediastinum), or 3 (<mediastinum but <=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites with no new lesions and no evidence of FDG-avid disease in bone marrow. Assessment was performed by Investigator according to Lugano classification using PET scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.

End point type

Secondary

End point timeframe

4-10 weeks after Cycle 6 Day 1 (Cycle length = 28 days)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: percentage of participants
number (confidence interval 95%)	55.6 (21.20 to 86.30)	15.4 (6.88 to 28.08)	70.6 (56.17 to 82.51)	68.6 (54.11 to 80.89)

Statistical Analysis 1

Comparison groups

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) v Chemotherapy-Containing Cohort: Arm C (BR)

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference in response rates

Point estimate

1.96

Confidence interval

level

95%

sides

2-sided

lower limit

-15.89

upper limit

19.81

Secondary: Percentage of Participants with CMR According to IRC as per Lugano Classification, Using PET Scan at Year 1

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End point title

Percentage of Participants with CMR According to IRC as per Lugano Classification, Using PET Scan at Year 1

End point description

CMR: a score 1 (no uptake above background), 2 (uptake <=mediastinum), or 3 (uptake <mediastinum but <=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites with no new lesions and no evidence of FDG-avid disease in bone marrow. Assessment was performed by an IRC according to Lugano classification using PET scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.

End point type

Secondary

End point timeframe

48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: percentage of participants
number (confidence interval 95%)	55.6 (21.20 to 86.30)	21.2 (11.06 to 34.70)	41.2 (27.58 to 55.83)	39.2 (25.84 to 53.89)

Statistical Analysis 1

Comparison groups

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) v Chemotherapy-Containing Cohort: Arm C (BR)

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference in response rates

Point estimate

1.96

Confidence interval

level

95%

sides

2-sided

lower limit

-17.07

upper limit

20.99

Secondary: Percentage of Participants with CMR According to Investigator as per Lugano Classification, Using PET Scan at Year 1

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End point title

Percentage of Participants with CMR According to Investigator as per Lugano Classification, Using PET Scan at Year 1

End point description

End point type

Secondary

End point timeframe

48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: percentage of participants
number (confidence interval 95%)	55.6 (21.20 to 86.30)	17.3 (8.23 to 30.33)	39.2 (25.84 to 53.89)	47.1 (32.93 to 61.54)

Statistical Analysis 1

Comparison groups

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) v Chemotherapy-Containing Cohort: Arm C (BR)

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference in response rates

Point estimate

-7.84

Confidence interval

level

95%

sides

2-sided

lower limit

-27.01

upper limit

11.32

Secondary: Percentage of Participants with Complete Response (CR) According to IRC as per Lugano Classification, Using Computed Tomography (CT) Scan

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End point title

Percentage of Participants with Complete Response (CR) According to IRC as per Lugano Classification, Using Computed Tomography (CT) Scan

End point description

CR: defined as reduction of longest transverse diameter of lesion (LDi) of target nodes/nodal masses to <=1.5 centimeters (cm), and no extralymphatic sites of disease; absence of non-measured lesions and new lesions; reduction of enlarged organs to normal; and normal/immunohistochemistry (IHC)-negative bone marrow morphology. Assessment was performed by an IRC according to Lugano classification using CT scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.

End point type

Secondary

End point timeframe

6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: percentage of participants
number (confidence interval 95%)
6−8 weeks after Cycle 6 Day 1	44.4 (13.70 to 78.80)	5.7 (1.18 to 15.66)	39.2 (25.84 to 53.89)	25.5 (14.33 to 39.63)
Year 1	55.6 (21.20 to 86.30)	13.2 (5.48 to 25.34)	27.5 (15.89 to 41.74)	23.5 (12.79 to 37.49)

Statistical Analysis 1

Statistical analysis description

At 6−8 weeks after Cycle 6 Day 1

Comparison groups

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) v Chemotherapy-Containing Cohort: Arm C (BR)

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference in response rates

Point estimate

13.73

Confidence interval

level

95%

sides

2-sided

lower limit

-4.24

upper limit

31.69

Statistical Analysis 2

Statistical analysis description

At Year 1

Comparison groups

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) v Chemotherapy-Containing Cohort: Arm C (BR)

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference in response rates

Point estimate

3.92

Confidence interval

level

95%

sides

2-sided

lower limit

-12.98

upper limit

20.82

Secondary: Percentage of Participants with CR According to Investigator as per Lugano Classification, Using CT Scan

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End point title

Percentage of Participants with CR According to Investigator as per Lugano Classification, Using CT Scan

End point description

CR: defined as reduction of LDi of target nodes/nodal masses to <=1.5 cm, and no extralymphatic sites of disease; absence of non-measured lesions and new lesions; reduction of enlarged organs to normal; and normal/IHC-negative bone marrow morphology. Assessment was performed by Investigator according to Lugano classification using CT scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.

End point type

Secondary

End point timeframe

4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: percentage of participants
number (confidence interval 95%)
4-10 weeks after Cycle 6 Day 1	22.2 (2.81 to 60.01)	5.7 (1.18 to 15.66)	15.7 (7.02 to 28.59)	31.4 (19.11 to 45.89)
Year 1	33.3 (7.49 to 70.07)	5.7 (1.18 to 15.66)	13.7 (5.70 to 26.26)	21.6 (11.29 to 35.32)

Statistical Analysis 1

Statistical analysis description

At 4-10 weeks after Cycle 6 Day 1

Comparison groups

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) v Chemotherapy-Containing Cohort: Arm C (BR)

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference in response rates

Point estimate

-15.69

Confidence interval

level

95%

sides

2-sided

lower limit

-31.87

upper limit

0.49

Statistical Analysis 2

Statistical analysis description

At Year 1

Comparison groups

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) v Chemotherapy-Containing Cohort: Arm C (BR)

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Difference in response rates

Point estimate

-7.84

Confidence interval

level

95%

sides

2-sided

lower limit

-22.56

upper limit

6.87

Secondary: Percentage of Participants with Objective Response (OR) According to IRC as per Lugano Classification, Using PET Scan

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End point title

Percentage of Participants with Objective Response (OR) According to IRC as per Lugano Classification, Using PET Scan

End point description

OR was defined as CMR or Partial Metabolic Response (PMR). CMR: a score 1 (no uptake above background), 2 (uptake <=mediastinum), or 3 (<mediastinum but <=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites with no new lesions and no evidence of FDG-avid disease in bone marrow. PMR: a score 4 (uptake moderately greater than [>] liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites with no new lesions and reduced residual uptake in bone marrow compared with baseline. Assessment was performed by an IRC according to Lugano classification using PET scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.

End point type

Secondary

End point timeframe

6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: percentage of participants
number (confidence interval 95%)
6−8 weeks after Cycle 6 Day 1	55.6 (21.20 to 86.30)	21.2 (11.06 to 34.70)	76.5 (62.51 to 87.21)	74.5 (60.37 to 85.67)
Year 1	66.7 (29.93 to 92.51)	32.7 (20.33 to 47.11)	45.1 (31.13 to 59.66)	51.0 (36.60 to 65.25)

No statistical analyses for this end point

Secondary: Percentage of Participants with OR According to Investigator as per Lugano Classification, Using PET Scan

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End point title

Percentage of Participants with OR According to Investigator as per Lugano Classification, Using PET Scan

End point description

OR was defined as CMR or PMR. CMR: a score 1 (no uptake above background), 2 (uptake <=mediastinum), or 3 (<mediastinum but <=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites with no new lesions and no evidence of FDG-avid disease in bone marrow. PMR: a score 4 (uptake moderately >liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites with no new lesions and reduced residual uptake in bone marrow compared with baseline. Assessment was performed by Investigator according to Lugano classification using PET scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.

End point type

Secondary

End point timeframe

4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: percentage of participants
number (confidence interval 95%)
4-10 weeks after Cycle 6 Day 1	55.6 (21.20 to 86.30)	28.8 (17.13 to 43.08)	76.5 (62.51 to 87.21)	76.5 (62.51 to 87.21)
Year 1	55.6 (21.20 to 86.30)	21.2 (11.06 to 34.70)	39.2 (25.84 to 53.89)	49.0 (34.75 to 63.40)

No statistical analyses for this end point

Secondary: Percentage of Participants with OR According to IRC as per Lugano Classification, Using CT Scan

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End point title

Percentage of Participants with OR According to IRC as per Lugano Classification, Using CT Scan

End point description

OR was defined as CR or Partial Response (PR). CR: reduction of LDi of target nodes/nodal masses to <=1.5 cm, and no extralymphatic sites of disease; absence of non-measured lesions and new lesions; reduction of enlarged organs to normal; and normal/IHC-negative bone marrow morphology. PR: greater than or equal to (>=) 50 percent (%) decrease in sum of the product of the perpendicular diameters (SPD) of up to 6 target measurable nodes and extra-nodal sites; absence/reduction/no increase in size of non-measured lesions; reduction in length of spleen at least >50% beyond normal; and no new lesions. Assessment was performed by an IRC according to Lugano classification using CT scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.

End point type

Secondary

End point timeframe

6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: percentage of participants
number (confidence interval 95%)
6−8 weeks after Cycle 6 Day 1	66.7 (29.93 to 92.51)	30.2 (18.34 to 44.34)	80.4 (66.88 to 90.18)	84.3 (71.41 to 92.98)
Year 1	66.7 (29.93 to 92.51)	22.6 (12.28 to 36.21)	41.2 (27.58 to 55.83)	60.8 (46.11 to 74.16)

No statistical analyses for this end point

Secondary: Percentage of Participants with OR According to Investigator as per Lugano Classification, Using CT Scan

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End point title

Percentage of Participants with OR According to Investigator as per Lugano Classification, Using CT Scan

End point description

OR was defined as CR or PR. CR: reduction of LDi of target nodes/nodal masses to <=1.5 cm, and no extralymphatic sites of disease; absence of non-measured lesions and new lesions; reduction of enlarged organs to normal; and normal/IHC-negative bone marrow morphology. PR: >=50% decrease in SPD of up to 6 target measurable nodes and extra-nodal sites; absence/reduction/no increase in size of non-measured lesions; reduction in length of spleen at least >50% beyond normal; and no new lesions. Assessment was performed by Investigator according to Lugano classification using CT scan. 95% CI for percentage of responders was calculated using Clopper-Pearson method.

End point type

Secondary

End point timeframe

4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: percentage of participants
number (confidence interval 95%)
4-10 weeks after Cycle 6 Day 1	55.6 (21.20 to 86.30)	32.1 (19.92 to 46.32)	74.5 (60.37 to 85.67)	78.4 (64.68 to 88.71)
Year 1	55.6 (21.20 to 86.30)	28.3 (16.79 to 42.35)	47.1 (32.93 to 61.54)	49.0 (34.75 to 63.40)

No statistical analyses for this end point

Secondary: Percentage of Participants with OR According to Investigator as per Lugano Classification, Using PET or CT Scan

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End point title

Percentage of Participants with OR According to Investigator as per Lugano Classification, Using PET or CT Scan

End point description

OR was defined as CMR/CR or PMR/PR. CMR, CR, PMR, and PR have been defined in previous endpoints, and are not repeated here due to space constraint. Assessment was performed by Investigator according to Lugano classification using PET scan or CT scan (if PET is missing).

End point type

Secondary

End point timeframe

Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: percentage of participants
number (confidence interval 95%)	66.7 (29.93 to 92.51)	36.5 (23.62 to 51.04)	80.4 (66.88 to 90.18)	80.4 (66.88 to 90.18)

No statistical analyses for this end point

Secondary: Duration of Response (DOR) According to Investigator as per Lugano Classification, Using PET or CT Scan

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End point title

Duration of Response (DOR) According to Investigator as per Lugano Classification, Using PET or CT Scan

End point description

DOR was defined as time from CMR/CR or PMR/PR until progressive disease (PD) or death due to any cause. CMR, CR, PMR, and PR have been defined in previous endpoints, and are not repeated here due to space constraint. PD: a score 4 (uptake moderately >liver) or 5 (uptake markedly >liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET scan or CT scan (if PET is missing). DOR was calculated using Kaplan-Meier method. ITT population. ‘Number of subjects analysed’=those evaluable for this outcome measure. '99999' indicates that upper limit of 95% confidence interval (CI) could not be calculated due to the low number of participants with event.

End point type

Secondary

End point timeframe

From CMR or PMR until disease progression or death due to any cause (assessed up to approximately 2.5 years)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	25	47	47
Units: months
median (confidence interval 95%)	32.46 (9.46 to 32.46)	15.79 (10.15 to 23.49)	24.87 (12.45 to 99999)	15.64 (12.09 to 99999)

Statistical Analysis 1

Statistical analysis description

Stratified Analysis: Strata were disease burden and DOR of prior cancer therapy.

Comparison groups

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) v Chemotherapy-Containing Cohort: Arm C (BR)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

1.27

Statistical Analysis 2

Statistical analysis description

Unstratified Analysis

Comparison groups

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) v Chemotherapy-Containing Cohort: Arm C (BR)

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.78

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

1.4

Secondary: Percentage of Participants with Disease Progression (According to Investigator as per Lugano Classification, Using PET or CT Scan) or Death

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End point title

Percentage of Participants with Disease Progression (According to Investigator as per Lugano Classification, Using PET or CT Scan) or Death

End point description

PD: a score 4 (uptake moderately >liver) or 5 (uptake markedly >liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET or CT scan.

End point type

Secondary

End point timeframe

Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: percentage of participants
number (not applicable)	44.4	86.5	41.2	52.9

No statistical analyses for this end point

Secondary: Progression-Free Survival (PFS) According to Investigator as per Lugano Classification, Using PET or CT Scan

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End point title

Progression-Free Survival (PFS) According to Investigator as per Lugano Classification, Using PET or CT Scan

End point description

PFS was defined as the period from the date of treatment initiation (Safety Run-in and Arm A) or randomization date (Arms B and C) until the date of disease progression, or death due to any cause. PD: a score 4 (uptake moderately >liver) or 5 (uptake markedly >liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET or CT scan. PFS was calculated using Kaplan-Meier method. ITT population. '99999' indicates that upper limit of 95% CI could not be calculated due to the low number of participants with event.

End point type

Secondary

End point timeframe

Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: months
median (confidence interval 95%)	35.09 (12.78 to 35.09)	6.57 (6.18 to 12.25)	27.63 (16.07 to 99999)	18.43 (16.92 to 99999)

Statistical Analysis 1

Statistical analysis description

Stratified Analysis: Strata were disease burden and PFS of prior cancer therapy.

Comparison groups

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) v Chemotherapy-Containing Cohort: Arm C (BR)

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

1.24

Statistical Analysis 2

Statistical analysis description

Unstratified Analysis

Comparison groups

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) v Chemotherapy-Containing Cohort: Arm C (BR)

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

1.36

Secondary: Percentage of Participants with Disease Progression (According to Investigator as per Lugano Classification, Using PET or CT Scan), Death, or Start of a New Anti-lymphoma Therapy

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End point title

Percentage of Participants with Disease Progression (According to Investigator as per Lugano Classification, Using PET or CT Scan), Death, or Start of a New Anti-lymphoma Therapy

End point description

End point type

Secondary

End point timeframe

Baseline until disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first (assessed up to approximately 2.5 years)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: percentage of participants
number (not applicable)	44.4	86.5	41.2	52.9

No statistical analyses for this end point

Secondary: Event-Free Survival (EFS) According to Investigator as per Lugano Classification, Using PET or CT Scan

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End point title

Event-Free Survival (EFS) According to Investigator as per Lugano Classification, Using PET or CT Scan

End point description

EFS was defined as the period from the date of treatment initiation (Safety Run-in and Arm A) or randomization date (Arms B and C) to the date of disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first. PD: a score 4 (uptake moderately >liver) or 5 (uptake markedly >liver and/or new lesions) with increase in intensity of uptake from baseline on PET 5-PS for individual target nodes/nodal lesions; new FDG-avid foci for extranodal lesions; new FDG-avid foci consistent with lymphoma for new lesions; or new or recurrent FDG-avid foci for bone marrow. Assessment was performed by Investigator according to Lugano classification using PET or CT scan. EFS was calculated using Kaplan-Meier method. ITT population. '99999' indicates that upper limit of 95% CI could not be calculated due to the low number of participants with event.

End point type

Secondary

End point timeframe

Baseline until disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first (assessed up to approximately 2.5 years)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: months
median (confidence interval 95%)	35.09 (12.78 to 35.09)	6.57 (6.18 to 12.25)	27.63 (16.07 to 99999)	18.43 (16.92 to 99999)

Statistical Analysis 1

Statistical analysis description

Stratified Analysis: Strata were disease burden and EFS of prior cancer therapy.

Comparison groups

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) v Chemotherapy-Containing Cohort: Arm C (BR)

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.69

Confidence interval

level

95%

sides

2-sided

lower limit

0.38

upper limit

1.24

Statistical Analysis 2

Statistical analysis description

Unstratified Analysis

Comparison groups

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) v Chemotherapy-Containing Cohort: Arm C (BR)

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.77

Confidence interval

level

95%

sides

2-sided

lower limit

0.43

upper limit

1.36

Secondary: Percentage of Participants who Died Due to Any Cause

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End point title

Percentage of Participants who Died Due to Any Cause

End point description

End point type

Secondary

End point timeframe

Baseline until death due to any cause (assessed up to approximately 2.5 years

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: percentage of participants
number (not applicable)	0	5.8	2.0	3.9

No statistical analyses for this end point

Secondary: Overall Survival (OS)

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End point title

Overall Survival (OS)

End point description

OS was defined as the period from the date of treatment initiation (Safety Run-in and Arm A) or randomization date (Arms B and C) to death due to any cause. For participants who are alive, OS was censored at the last contact. OS was calculated using Kaplan-Meier method. ITT population. '9999' indicates that median and corresponding 95% CI could not be estimated due to higher number of censored participants.

End point type

Secondary

End point timeframe

Baseline until death due to any cause (assessed up to approximately 2.5 years)

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Number of subjects analysed	9	52	51	51
Units: months
median (confidence interval 95%)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)

Statistical Analysis 1

Statistical analysis description

Stratified Analysis: Strata were disease burden and OS of prior cancer therapy.

Comparison groups

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) v Chemotherapy-Containing Cohort: Arm C (BR)

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.48

Confidence interval

level

95%

sides

2-sided

lower limit

0.04

upper limit

5.37

Statistical Analysis 2

Statistical analysis description

Unstratified Analysis

Comparison groups

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR) v Chemotherapy-Containing Cohort: Arm C (BR)

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Hazard ratio (HR)

Point estimate

0.51

Confidence interval

level

95%

sides

2-sided

lower limit

0.05

upper limit

5.63

Secondary: Apparent Clearance (CL) of Venetoclax

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End point title

Apparent Clearance (CL) of Venetoclax ^[1]

End point description

CL is a quantitative measure of the rate at which a drug substance is removed from the body.

End point type

Secondary

End point timeframe

Pre-dose (within 30 minutes), and 2, 4, 6, 8 hours post-dose on Cycle 1 Day 1; pre-dose (within 30 minutes) on Cycle 1 Days 8, 15, 22; pre-dose (within 30 minutes) and 4 hours post-dose on Day 1 of Cycles 4 and 6 (Cycle length = 28 days)

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only applicable for the arms containing venetoclax treatment

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)
Number of subjects analysed	0 ^[2]	0 ^[3]	0 ^[4]
Units: milliliters per hour (mL/hour)
arithmetic mean (standard deviation)	( )	( )	( )

Notes
[2] - Pharmacokinetics timepoints and daily dosing of venetoclax did not permit an assessment of CL.
[3] - Pharmacokinetics timepoints and daily dosing of venetoclax did not permit an assessment of CL.
[4] - Pharmacokinetics timepoints and daily dosing of venetoclax did not permit an assessment of CL.

No statistical analyses for this end point

Secondary: Apparent Volume of Distribution (Vd) of Venetoclax

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End point title

Apparent Volume of Distribution (Vd) of Venetoclax ^[5]

End point description

Vd was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

End point type

Secondary

End point timeframe

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only applicable for the arms containing venetoclax treatment

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)
Number of subjects analysed	0 ^[6]	0 ^[7]	0 ^[8]
Units: milliliters (mL)
arithmetic mean (standard deviation)	( )	( )	( )

Notes
[6] - Pharmacokinetics timepoints and daily dosing of venetoclax did not permit an assessment of Vd.
[7] - Pharmacokinetics timepoints and daily dosing of venetoclax did not permit an assessment of Vd.
[8] - Pharmacokinetics timepoints and daily dosing of venetoclax did not permit an assessment of Vd.

No statistical analyses for this end point

Secondary: Time to Maximum Plasma Concentration (Tmax) of Venetoclax

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End point title

Time to Maximum Plasma Concentration (Tmax) of Venetoclax ^[9]

End point description

End point type

Secondary

End point timeframe

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only applicable for the arms containing venetoclax treatment

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)
Number of subjects analysed	9	51	46
Units: hours
median (full range (min-max))	8.00 (4.00 to 8.08)	6.00 (1.95 to 8.18)	6.21 (1.98 to 9.22)

No statistical analyses for this end point

Secondary: Maximum Plasma Concentration (Cmax) of Venetoclax

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End point title

Maximum Plasma Concentration (Cmax) of Venetoclax ^[10]

End point description

End point type

Secondary

End point timeframe

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only applicable for the arms containing venetoclax treatment

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)
Number of subjects analysed	9	51	46
Units: nanograms per milliliter (ng/mL)
arithmetic mean (standard deviation)	1350 ( 427 )	1220 ( 478 )	1340 ( 460 )

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration-Time Curve from Time 0 to Last Observed Concentration (AUClast) of Venetoclax

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End point title

Area Under the Plasma Concentration-Time Curve from Time 0 to Last Observed Concentration (AUClast) of Venetoclax ^[11]

End point description

Area under the plasma concentration versus time curve from zero to the last measured concentration (AUClast).

End point type

Secondary

End point timeframe

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only applicable for the arms containing venetoclax treatment

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)
Number of subjects analysed	9	51	46
Units: hours*ng/mL
arithmetic mean (standard deviation)	5310 ( 1730 )	4950 ( 1950 )	5500 ( 2270 )

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration-Time Curve from Time 0 to 8 Hours Post Dose (AUC0-8h) of Venetoclax

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End point title

Area Under the Plasma Concentration-Time Curve from Time 0 to 8 Hours Post Dose (AUC0-8h) of Venetoclax ^[12]

End point description

Area under the plasma concentration versus time curve from time 0 (pre-dose) to 8 hours post dose (AUC0-8h).

End point type

Secondary

End point timeframe

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was only applicable for the arms containing venetoclax treatment

End point values	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)
Number of subjects analysed	6	30	23
Units: hours*ng/mL
arithmetic mean (standard deviation)	5240 ( 1860 )	4820 ( 1980 )	5330 ( 2270 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Baseline up to approximately 2.5 years

Adverse event reporting additional description

Safety-evaluable population included participants who received at least one dose of any study treatment.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

21.0

Reporting group title

Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)

Reporting group description

Reporting group title

Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)

Reporting group description

Reporting group title

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)

Reporting group description

Reporting group title

Chemotherapy-Containing Cohort: Arm C (BR)

Reporting group description

Participants received rituximab 375 mg/m^2 IV infusion on Day 1 of each 28-day cycle and bendamustine 90 mg/m^2 IV infusion on Days 1 and 2 of each 28-day cycle, for 6 cycles.

Serious adverse events	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Total subjects affected by serious adverse events
subjects affected / exposed	4 / 9 (44.44%)	16 / 52 (30.77%)	26 / 49 (53.06%)	12 / 50 (24.00%)
number of deaths (all causes)	0	3	1	2
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myelodysplastic syndrome
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	3 / 49 (6.12%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
LUNG ADENOCARCINOMA
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	0 / 49 (0.00%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
METASTATIC MALIGNANT MELANOMA
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	0 / 49 (0.00%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Embolism
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhage
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Renal stone removal
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Cytokine release syndrome
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	0 / 49 (0.00%)	2 / 50 (4.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Pleuritic pain
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	0 / 49 (0.00%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary haemorrhage
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 9 (0.00%)	2 / 52 (3.85%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute left ventricular failure
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
ACUTE CORONARY SYNDROME
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
LEFT VENTRICULAR FAILURE
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
ATRIAL FIBRILLATION
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	0 / 49 (0.00%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	1 / 49 (2.04%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aplastic anaemia
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	6 / 49 (12.24%)	3 / 50 (6.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	6 / 6	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
NEUTROPENIA
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Diplopia
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Erosive oesophagitis
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis chronic
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	0 / 49 (0.00%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Urticaria
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal colic
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Acute sinusitis
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atypical pneumonia
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	0 / 49 (0.00%)	2 / 50 (4.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cystitis
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cytomegalovirus infection
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	0 / 49 (0.00%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Herpes zoster disseminated
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lung infection
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	2 / 49 (4.08%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal candidiasis
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumocystis jirovecii pneumonia
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	3 / 49 (6.12%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 9 (0.00%)	2 / 52 (3.85%)	3 / 49 (6.12%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 0	1 / 2	3 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia pseudomonal
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	0 / 49 (0.00%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin infection
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
HERPES SIMPLEX
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tumour lysis syndrome
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	1 / 49 (2.04%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)	Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)	Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)	Chemotherapy-Containing Cohort: Arm C (BR)
Total subjects affected by non serious adverse events
subjects affected / exposed	9 / 9 (100.00%)	49 / 52 (94.23%)	49 / 49 (100.00%)	48 / 50 (96.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	1 / 49 (2.04%)	3 / 50 (6.00%)
occurrences all number	0	4	1	4
COLON ADENOMA
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Vascular disorders
Flushing
subjects affected / exposed	1 / 9 (11.11%)	1 / 52 (1.92%)	0 / 49 (0.00%)	2 / 50 (4.00%)
occurrences all number	1	1	0	2
Hypertension
subjects affected / exposed	1 / 9 (11.11%)	3 / 52 (5.77%)	1 / 49 (2.04%)	2 / 50 (4.00%)
occurrences all number	1	3	1	2
Hypotension
subjects affected / exposed	2 / 9 (22.22%)	2 / 52 (3.85%)	3 / 49 (6.12%)	2 / 50 (4.00%)
occurrences all number	3	2	5	2
Orthostatic hypotension
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 9 (11.11%)	4 / 52 (7.69%)	5 / 49 (10.20%)	4 / 50 (8.00%)
occurrences all number	1	4	8	5
Catheter site pain
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Chills
subjects affected / exposed	1 / 9 (11.11%)	5 / 52 (9.62%)	3 / 49 (6.12%)	2 / 50 (4.00%)
occurrences all number	1	6	3	3
Fatigue
subjects affected / exposed	3 / 9 (33.33%)	13 / 52 (25.00%)	21 / 49 (42.86%)	15 / 50 (30.00%)
occurrences all number	6	14	29	22
Influenza like illness
subjects affected / exposed	2 / 9 (22.22%)	1 / 52 (1.92%)	2 / 49 (4.08%)	2 / 50 (4.00%)
occurrences all number	2	1	3	2
Malaise
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	3 / 49 (6.12%)	0 / 50 (0.00%)
occurrences all number	0	1	4	0
Mass
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	1 / 50 (2.00%)
occurrences all number	1	0	0	1
Peripheral swelling
subjects affected / exposed	1 / 9 (11.11%)	1 / 52 (1.92%)	2 / 49 (4.08%)	0 / 50 (0.00%)
occurrences all number	3	1	2	0
Pyrexia
subjects affected / exposed	1 / 9 (11.11%)	5 / 52 (9.62%)	10 / 49 (20.41%)	9 / 50 (18.00%)
occurrences all number	1	6	15	16
OEDEMA PERIPHERAL
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	1 / 49 (2.04%)	3 / 50 (6.00%)
occurrences all number	0	1	2	3
Immune system disorders
HYPOGAMMAGLOBULINAEMIA
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	4 / 49 (8.16%)	2 / 50 (4.00%)
occurrences all number	0	0	4	2
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	3 / 9 (33.33%)	6 / 52 (11.54%)	12 / 49 (24.49%)	12 / 50 (24.00%)
occurrences all number	4	6	14	15
Dyspnoea
subjects affected / exposed	1 / 9 (11.11%)	1 / 52 (1.92%)	6 / 49 (12.24%)	2 / 50 (4.00%)
occurrences all number	1	1	8	3
Lung consolidation
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Nasal congestion
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	2 / 49 (4.08%)	3 / 50 (6.00%)
occurrences all number	0	1	2	3
Oropharyngeal pain
subjects affected / exposed	1 / 9 (11.11%)	1 / 52 (1.92%)	2 / 49 (4.08%)	1 / 50 (2.00%)
occurrences all number	1	1	2	1
Productive cough
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	2 / 49 (4.08%)	5 / 50 (10.00%)
occurrences all number	0	1	3	10
Rhinorrhoea
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	4 / 50 (8.00%)
occurrences all number	0	0	1	5
Throat irritation
subjects affected / exposed	1 / 9 (11.11%)	1 / 52 (1.92%)	0 / 49 (0.00%)	1 / 50 (2.00%)
occurrences all number	1	1	0	1
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 9 (11.11%)	2 / 52 (3.85%)	2 / 49 (4.08%)	0 / 50 (0.00%)
occurrences all number	1	2	2	0
Hallucination
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Insomnia
subjects affected / exposed	3 / 9 (33.33%)	1 / 52 (1.92%)	7 / 49 (14.29%)	2 / 50 (4.00%)
occurrences all number	3	1	7	2
Investigations
Aspartate aminotransferase increased
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	5 / 49 (10.20%)	2 / 50 (4.00%)
occurrences all number	0	0	5	3
Blood alkaline phosphatase increased
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	2 / 49 (4.08%)	3 / 50 (6.00%)
occurrences all number	2	0	2	5
Blood creatinine increased
subjects affected / exposed	0 / 9 (0.00%)	3 / 52 (5.77%)	2 / 49 (4.08%)	0 / 50 (0.00%)
occurrences all number	0	3	2	0
Gamma−glutamyltransferase increased
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	0 / 49 (0.00%)	5 / 50 (10.00%)
occurrences all number	0	0	0	8
Weight decreased
subjects affected / exposed	1 / 9 (11.11%)	4 / 52 (7.69%)	8 / 49 (16.33%)	0 / 50 (0.00%)
occurrences all number	1	4	8	0
Weight increased
subjects affected / exposed	0 / 9 (0.00%)	3 / 52 (5.77%)	2 / 49 (4.08%)	0 / 50 (0.00%)
occurrences all number	0	3	2	0
White blood cell count decreased
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	4 / 49 (8.16%)	1 / 50 (2.00%)
occurrences all number	0	0	5	9
Injury, poisoning and procedural complications
Infusion related reaction
subjects affected / exposed	2 / 9 (22.22%)	18 / 52 (34.62%)	10 / 49 (20.41%)	7 / 50 (14.00%)
occurrences all number	2	19	13	8
Laceration
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences all number	1	0	1	0
Limb injury
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	1 / 9 (11.11%)	2 / 52 (3.85%)	2 / 49 (4.08%)	0 / 50 (0.00%)
occurrences all number	1	2	6	0
Palpitations
subjects affected / exposed	2 / 9 (22.22%)	0 / 52 (0.00%)	0 / 49 (0.00%)	1 / 50 (2.00%)
occurrences all number	2	0	0	1
Sinus tachycardia
subjects affected / exposed	0 / 9 (0.00%)	2 / 52 (3.85%)	3 / 49 (6.12%)	1 / 50 (2.00%)
occurrences all number	0	2	4	1
Tachycardia
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	3 / 49 (6.12%)	0 / 50 (0.00%)
occurrences all number	0	1	3	0
Nervous system disorders
Burning sensation
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Dizziness
subjects affected / exposed	1 / 9 (11.11%)	4 / 52 (7.69%)	8 / 49 (16.33%)	3 / 50 (6.00%)
occurrences all number	1	5	8	3
Dysgeusia
subjects affected / exposed	0 / 9 (0.00%)	3 / 52 (5.77%)	3 / 49 (6.12%)	4 / 50 (8.00%)
occurrences all number	0	3	3	4
Peripheral sensory neuropathy
subjects affected / exposed	1 / 9 (11.11%)	1 / 52 (1.92%)	0 / 49 (0.00%)	1 / 50 (2.00%)
occurrences all number	1	1	0	1
Presyncope
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Headache
subjects affected / exposed	3 / 9 (33.33%)	5 / 52 (9.62%)	8 / 49 (16.33%)	6 / 50 (12.00%)
occurrences all number	4	7	11	9
COGNITIVE DISORDER
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 9 (22.22%)	3 / 52 (5.77%)	19 / 49 (38.78%)	8 / 50 (16.00%)
occurrences all number	2	3	26	8
Leukopenia
subjects affected / exposed	2 / 9 (22.22%)	5 / 52 (9.62%)	6 / 49 (12.24%)	3 / 50 (6.00%)
occurrences all number	2	7	10	3
Neutropenia
subjects affected / exposed	5 / 9 (55.56%)	14 / 52 (26.92%)	30 / 49 (61.22%)	17 / 50 (34.00%)
occurrences all number	13	36	96	58
Thrombocytopenia
subjects affected / exposed	3 / 9 (33.33%)	7 / 52 (13.46%)	28 / 49 (57.14%)	8 / 50 (16.00%)
occurrences all number	15	9	72	15
Eye disorders
Vision blurred
subjects affected / exposed	1 / 9 (11.11%)	1 / 52 (1.92%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences all number	1	1	1	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences all number	1	0	1	0
Abdominal distension
subjects affected / exposed	0 / 9 (0.00%)	5 / 52 (9.62%)	0 / 49 (0.00%)	1 / 50 (2.00%)
occurrences all number	0	5	0	1
Abdominal pain
subjects affected / exposed	2 / 9 (22.22%)	6 / 52 (11.54%)	6 / 49 (12.24%)	5 / 50 (10.00%)
occurrences all number	3	7	8	5
Abdominal pain upper
subjects affected / exposed	1 / 9 (11.11%)	2 / 52 (3.85%)	3 / 49 (6.12%)	3 / 50 (6.00%)
occurrences all number	1	2	3	3
Constipation
subjects affected / exposed	3 / 9 (33.33%)	5 / 52 (9.62%)	10 / 49 (20.41%)	17 / 50 (34.00%)
occurrences all number	4	5	10	19
Diarrhoea
subjects affected / exposed	5 / 9 (55.56%)	21 / 52 (40.38%)	24 / 49 (48.98%)	14 / 50 (28.00%)
occurrences all number	14	28	47	21
Dyspepsia
subjects affected / exposed	2 / 9 (22.22%)	3 / 52 (5.77%)	0 / 49 (0.00%)	2 / 50 (4.00%)
occurrences all number	2	3	0	2
Dysphagia
subjects affected / exposed	1 / 9 (11.11%)	3 / 52 (5.77%)	1 / 49 (2.04%)	1 / 50 (2.00%)
occurrences all number	1	3	1	1
Large intestine polyp
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Mouth ulceration
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	3 / 49 (6.12%)	2 / 50 (4.00%)
occurrences all number	1	0	4	2
Nausea
subjects affected / exposed	7 / 9 (77.78%)	14 / 52 (26.92%)	32 / 49 (65.31%)	23 / 50 (46.00%)
occurrences all number	12	16	58	35
Stomatitis
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	5 / 49 (10.20%)	1 / 50 (2.00%)
occurrences all number	0	0	5	1
Vomiting
subjects affected / exposed	4 / 9 (44.44%)	7 / 52 (13.46%)	23 / 49 (46.94%)	13 / 50 (26.00%)
occurrences all number	7	12	43	18
Skin and subcutaneous tissue disorders
Erythema
subjects affected / exposed	1 / 9 (11.11%)	1 / 52 (1.92%)	3 / 49 (6.12%)	2 / 50 (4.00%)
occurrences all number	1	1	3	2
Pruritus
subjects affected / exposed	1 / 9 (11.11%)	3 / 52 (5.77%)	1 / 49 (2.04%)	4 / 50 (8.00%)
occurrences all number	2	3	1	6
Psoriasis
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	2	0	0	0
Yellow skin
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	2 / 9 (22.22%)	0 / 52 (0.00%)	1 / 49 (2.04%)	2 / 50 (4.00%)
occurrences all number	2	0	1	2
Renal colic
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 9 (11.11%)	3 / 52 (5.77%)	5 / 49 (10.20%)	2 / 50 (4.00%)
occurrences all number	1	3	5	3
Back pain
subjects affected / exposed	3 / 9 (33.33%)	2 / 52 (3.85%)	0 / 49 (0.00%)	7 / 50 (14.00%)
occurrences all number	3	2	0	8
Joint swelling
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Musculoskeletal pain
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Musculoskeletal stiffness
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	3	0	0	0
Myalgia
subjects affected / exposed	0 / 9 (0.00%)	2 / 52 (3.85%)	4 / 49 (8.16%)	1 / 50 (2.00%)
occurrences all number	0	2	6	1
Periarthritis
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Infections and infestations
Aspergillus infection
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Bronchitis
subjects affected / exposed	0 / 9 (0.00%)	2 / 52 (3.85%)	6 / 49 (12.24%)	1 / 50 (2.00%)
occurrences all number	0	2	8	1
Cellulitis
subjects affected / exposed	1 / 9 (11.11%)	1 / 52 (1.92%)	0 / 49 (0.00%)	2 / 50 (4.00%)
occurrences all number	1	2	0	2
Conjunctivitis
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	0 / 49 (0.00%)	4 / 50 (8.00%)
occurrences all number	0	0	0	5
Herpes zoster
subjects affected / exposed	1 / 9 (11.11%)	1 / 52 (1.92%)	2 / 49 (4.08%)	1 / 50 (2.00%)
occurrences all number	1	1	2	1
Lower respiratory tract infection
subjects affected / exposed	0 / 9 (0.00%)	2 / 52 (3.85%)	3 / 49 (6.12%)	0 / 50 (0.00%)
occurrences all number	0	2	3	0
Lung infection
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	4 / 49 (8.16%)	0 / 50 (0.00%)
occurrences all number	0	0	4	0
Mycobacterium kansasii infection
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Nasopharyngitis
subjects affected / exposed	3 / 9 (33.33%)	4 / 52 (7.69%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences all number	3	4	3	0
Oral candidiasis
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	4 / 49 (8.16%)	2 / 50 (4.00%)
occurrences all number	1	0	6	2
Oral herpes
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	3 / 49 (6.12%)	1 / 50 (2.00%)
occurrences all number	0	0	6	2
Perineal abscess
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	0 / 49 (0.00%)	0 / 50 (0.00%)
occurrences all number	1	0	0	0
Rhinitis
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	1 / 49 (2.04%)	4 / 50 (8.00%)
occurrences all number	0	0	1	5
Sinusitis
subjects affected / exposed	1 / 9 (11.11%)	3 / 52 (5.77%)	3 / 49 (6.12%)	4 / 50 (8.00%)
occurrences all number	1	3	5	4
Upper respiratory tract infection
subjects affected / exposed	2 / 9 (22.22%)	6 / 52 (11.54%)	6 / 49 (12.24%)	4 / 50 (8.00%)
occurrences all number	3	9	8	4
Urinary tract infection
subjects affected / exposed	1 / 9 (11.11%)	4 / 52 (7.69%)	5 / 49 (10.20%)	2 / 50 (4.00%)
occurrences all number	1	4	10	4
SUBCUTANEOUS ABSCESS
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	1 / 49 (2.04%)	0 / 50 (0.00%)
occurrences all number	1	0	1	0
PNEUMONIA
subjects affected / exposed	1 / 9 (11.11%)	0 / 52 (0.00%)	4 / 49 (8.16%)	2 / 50 (4.00%)
occurrences all number	1	0	5	3
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 9 (0.00%)	5 / 52 (9.62%)	10 / 49 (20.41%)	7 / 50 (14.00%)
occurrences all number	0	6	13	7
Hyperglycaemia
subjects affected / exposed	0 / 9 (0.00%)	2 / 52 (3.85%)	3 / 49 (6.12%)	1 / 50 (2.00%)
occurrences all number	0	3	3	1
Hypokalaemia
subjects affected / exposed	1 / 9 (11.11%)	6 / 52 (11.54%)	13 / 49 (26.53%)	4 / 50 (8.00%)
occurrences all number	2	7	18	4
Hypomagnesaemia
subjects affected / exposed	0 / 9 (0.00%)	1 / 52 (1.92%)	6 / 49 (12.24%)	0 / 50 (0.00%)
occurrences all number	0	1	7	0
Hyponatraemia
subjects affected / exposed	0 / 9 (0.00%)	0 / 52 (0.00%)	3 / 49 (6.12%)	0 / 50 (0.00%)
occurrences all number	0	0	3	0
Hypophosphataemia
subjects affected / exposed	0 / 9 (0.00%)	3 / 52 (5.77%)	5 / 49 (10.20%)	1 / 50 (2.00%)
occurrences all number	0	4	6	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

24 Mar 2014

The protocol was amended to clarify instructions for detection and reporting of liver function abnormalities; and for addition of EudraCT number 2014-000576-26.

25 Apr 2014

The protocol was amended to allow investigator’s choice of a Chemotherapy Free Cohort or a Chemotherapy-Containing Regimen. Participants assigned to the Chemotherapy-Containing Cohort were subsequently randomized to standard chemo-immunotherapy (bendamustine + rituximab, BR) versus BR + venetoclax. This change was made in response to concerns that participants who required a rapid response to treatment should not be randomized to an unproven Chemotherapy Free regimen; Rituximab dosing regimen in Arm A (Chemotherapy-Free cohort) was modified to align more closely with published data. The revised regimen was: Rituximab 375 mg/m^2 on Cycle 1 on Days 1, 8, 15, and 22, followed by 5 additional doses of rituximab administered every 8 weeks on Day 1 of Cycles 4, 6, 8, 10, and 12.

06 Jan 2015

The standard lymphoma response criteria were updated; Participants with prior exposure to hepatitis B, as manifest by hepatitis B virus (HBV) serologies showing hepatitis B core antibody−positive and hepatitis B surface antigen−negative were previously excluded from the study; It was clarified that non-vasectomized males must practice birth control and refrain from sperm donation for 6 months after the last dose of rituximab; The rationale for sample size determination was clarified; It was clarified how the tissue punch was to be obtained for tissue microarrays; The Year 1 assessment could now be performed up to 4 weeks, instead of 2 weeks, to allow flexibility on the timing.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase II, Open-Label Study Evaluating the Safety and Efficacy of GDC-0199 (ABT-199) Plus Bendamustine Plus Rituximab (BR) in Comparison with BR Alone or GDC-0199 Plus Rituximab (R) in Patients with Relapsed and Refractory Follicular Non-Hodgkin’s Lymphoma

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants with Complete Metabolic Response (CMR) According to Independent Review Committee (IRC) as per Lugano Classification, Using Positron Emission Tomography (PET) Scan at Primary Response Assessment (PRA)

Primary: Percentage of Participants with Complete Metabolic Response (CMR) According to Independent Review Committee (IRC) as per Lugano Classification, Using Positron Emission Tomography (PET) Scan at Primary Response Assessment (PRA)

Secondary: Percentage of Participants with CMR According to Investigator as per Lugano Classification, Using PET Scan at PRA

Secondary: Percentage of Participants with CMR According to Investigator as per Lugano Classification, Using PET Scan at PRA

Secondary: Percentage of Participants with CMR According to IRC as per Lugano Classification, Using PET Scan at Year 1

Secondary: Percentage of Participants with CMR According to IRC as per Lugano Classification, Using PET Scan at Year 1

Secondary: Percentage of Participants with CMR According to Investigator as per Lugano Classification, Using PET Scan at Year 1

Secondary: Percentage of Participants with CMR According to Investigator as per Lugano Classification, Using PET Scan at Year 1

Secondary: Percentage of Participants with Complete Response (CR) According to IRC as per Lugano Classification, Using Computed Tomography (CT) Scan

Secondary: Percentage of Participants with Complete Response (CR) According to IRC as per Lugano Classification, Using Computed Tomography (CT) Scan

Secondary: Percentage of Participants with CR According to Investigator as per Lugano Classification, Using CT Scan

Secondary: Percentage of Participants with CR According to Investigator as per Lugano Classification, Using CT Scan

Secondary: Percentage of Participants with Objective Response (OR) According to IRC as per Lugano Classification, Using PET Scan

Secondary: Percentage of Participants with Objective Response (OR) According to IRC as per Lugano Classification, Using PET Scan

Secondary: Percentage of Participants with OR According to Investigator as per Lugano Classification, Using PET Scan

Secondary: Percentage of Participants with OR According to Investigator as per Lugano Classification, Using PET Scan

Secondary: Percentage of Participants with OR According to IRC as per Lugano Classification, Using CT Scan

Secondary: Percentage of Participants with OR According to IRC as per Lugano Classification, Using CT Scan

Secondary: Percentage of Participants with OR According to Investigator as per Lugano Classification, Using CT Scan

Secondary: Percentage of Participants with OR According to Investigator as per Lugano Classification, Using CT Scan

Secondary: Percentage of Participants with OR According to Investigator as per Lugano Classification, Using PET or CT Scan

Secondary: Percentage of Participants with OR According to Investigator as per Lugano Classification, Using PET or CT Scan

Secondary: Duration of Response (DOR) According to Investigator as per Lugano Classification, Using PET or CT Scan

Secondary: Duration of Response (DOR) According to Investigator as per Lugano Classification, Using PET or CT Scan

Secondary: Percentage of Participants with Disease Progression (According to Investigator as per Lugano Classification, Using PET or CT Scan) or Death

Secondary: Percentage of Participants with Disease Progression (According to Investigator as per Lugano Classification, Using PET or CT Scan) or Death

Secondary: Progression-Free Survival (PFS) According to Investigator as per Lugano Classification, Using PET or CT Scan

Secondary: Progression-Free Survival (PFS) According to Investigator as per Lugano Classification, Using PET or CT Scan

Secondary: Percentage of Participants with Disease Progression (According to Investigator as per Lugano Classification, Using PET or CT Scan), Death, or Start of a New Anti-lymphoma Therapy

Secondary: Percentage of Participants with Disease Progression (According to Investigator as per Lugano Classification, Using PET or CT Scan), Death, or Start of a New Anti-lymphoma Therapy

Secondary: Event-Free Survival (EFS) According to Investigator as per Lugano Classification, Using PET or CT Scan

Secondary: Event-Free Survival (EFS) According to Investigator as per Lugano Classification, Using PET or CT Scan

Secondary: Percentage of Participants who Died Due to Any Cause

Secondary: Percentage of Participants who Died Due to Any Cause

Secondary: Overall Survival (OS)

Secondary: Overall Survival (OS)

Secondary: Apparent Clearance (CL) of Venetoclax

Secondary: Apparent Clearance (CL) of Venetoclax

Secondary: Apparent Volume of Distribution (Vd) of Venetoclax

Secondary: Apparent Volume of Distribution (Vd) of Venetoclax

Secondary: Time to Maximum Plasma Concentration (Tmax) of Venetoclax

Secondary: Time to Maximum Plasma Concentration (Tmax) of Venetoclax

Secondary: Maximum Plasma Concentration (Cmax) of Venetoclax

Secondary: Maximum Plasma Concentration (Cmax) of Venetoclax

Secondary: Area Under the Plasma Concentration-Time Curve from Time 0 to Last Observed Concentration (AUClast) of Venetoclax

Secondary: Area Under the Plasma Concentration-Time Curve from Time 0 to Last Observed Concentration (AUClast) of Venetoclax

Secondary: Area Under the Plasma Concentration-Time Curve from Time 0 to 8 Hours Post Dose (AUC0-8h) of Venetoclax

Secondary: Area Under the Plasma Concentration-Time Curve from Time 0 to 8 Hours Post Dose (AUC0-8h) of Venetoclax

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase II, Open-Label Study Evaluating the Safety and Efficacy of GDC-0199 (ABT-199) Plus Bendamustine Plus Rituximab (BR) in Comparison with BR Alone or GDC-0199 Plus Rituximab (R) in Patients with Relapsed and Refractory Follicular Non-Hodgkin’s Lymphoma