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A Study Evaluating the Safety and Efficacy of Venetoclax (GDC-0199) Plus Bendamustine + Rituximab (BR) in Comparison With BR or Venetoclax Plus Rituximab in Participants With Relapsed and Refractory Follicular Non-Hodgkin's Lymphoma (fNHL)

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT02187861
Collaborator
AbbVie (Industry)
163
Enrollment
71
Locations
4
Arms
39.5
Actual Duration (Months)
2.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This open-label, international, multicenter study will investigate the safety and efficacy of venetoclax (GDC-0199) in combination with bendamustine plus rituximab (venetoclax + BR) compared with BR alone in participants with relapsed and refractory fNHL, comparing two chemotherapy-containing regimens (Chemotherapy-Containing Cohort). In addition, an exploratory analysis of the safety and efficacy of venetoclax in combination with rituximab (venetoclax + rituximab), a chemotherapy-free regimen, will be performed (Chemotherapy-Free Cohort). Assignment to the Chemotherapy-Containing or Chemotherapy-Free Cohort will be decided at the discretion of the Investigator, unless one of the cohorts is not open to enrollment; in which case, participants may be enrolled only to the open cohort. The first 6 participants enrolled in the Chemotherapy-Containing Cohort (or more if required) will comprise the Safety Run-In group for Treatment Arm B, dosing venetoclax at 600 milligrams (mg) in combination with BR. Once a dose has been chosen from the Safety Run-In Period, randomization to the two treatment arms of the Chemotherapy-Containing Cohort (Arms B and C) will begin.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
163 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Dec 1, 2014
Actual Primary Completion Date :
Sep 27, 2016
Actual Study Completion Date :
Mar 16, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)

Participants will receive 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 will continue until first 9 participants complete the safety observation window of 28 days. Participants will continue receiving the same treatment as decided for Arm B.

Drug: Venetoclax
Venetoclax will be administered as per the schedule specified under arm description.
Other Names:
  • GDC-0199
  • ABT-199

    • Drug: Bendamustine
    Bendamustine will be administered as per the schedule specified under arm description.
    Other Names:
  • Levact

    • Drug: Rituximab
    Rituximab will be administered as per the schedule specified under arm description.
    Other Names:
  • MabThera
  • Rituxan

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

    Participants will receive 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 will be of 28 days.

    Drug: Venetoclax
    Venetoclax will be administered as per the schedule specified under arm description.
    Other Names:
  • GDC-0199
  • ABT-199

    • Drug: Rituximab
    Rituximab will be administered as per the schedule specified under arm description.
    Other Names:
  • MabThera
  • Rituxan

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

    Participants will receive venetoclax at doses decided from safety run-in 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.

    Drug: Venetoclax
    Venetoclax will be administered as per the schedule specified under arm description.
    Other Names:
  • GDC-0199
  • ABT-199

    • Drug: Bendamustine
    Bendamustine will be administered as per the schedule specified under arm description.
    Other Names:
  • Levact

    • Drug: Rituximab
    Rituximab will be administered as per the schedule specified under arm description.
    Other Names:
  • MabThera
  • Rituxan

    		•
    Active Comparator: Chemotherapy-Containing Cohort: Arm C (BR)

    Participants will receive 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.

    Drug: Bendamustine
    Bendamustine will be administered as per the schedule specified under arm description.
    Other Names:
  • Levact

    • Drug: Rituximab
    Rituximab will be administered as per the schedule specified under arm description.
    Other Names:
  • MabThera
  • Rituxan

    		•

    Outcome Measures

    Primary Outcome Measures

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

      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.

    Secondary Outcome Measures

    1. Percentage of Participants With CMR According to Investigator as Per Lugano Classification, Using PET Scan at PRA [4-10 weeks after Cycle 6 Day 1 (Cycle length = 28 days)]

      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.

    2. Percentage of Participants With CMR According to IRC as Per Lugano Classification, Using PET Scan at Year 1 [48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)]

      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.

    3. Percentage of Participants With CMR According to Investigator as Per Lugano Classification, Using PET Scan at Year 1 [48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)]

      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.

    4. Percentage of Participants With Complete Response (CR) According to IRC as Per Lugano Classification, Using Computed Tomography (CT) Scan [6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)]

      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.

    5. Percentage of Participants With CR According to Investigator as Per Lugano Classification, Using CT Scan [4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)]

      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.

    6. Percentage of Participants With Objective Response (OR) According to IRC as Per Lugano Classification, Using PET Scan [6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)]

      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.

    7. Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using PET Scan [4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)]

      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.

    8. Percentage of Participants With OR According to IRC as Per Lugano Classification, Using CT Scan [6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)]

      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.

    9. Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using CT Scan [4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)]

      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.

    10. Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using PET or CT Scan [Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)]

      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).

    11. Duration of Response (DOR) According to Investigator as Per Lugano Classification, Using PET or CT Scan [From CMR or PMR until disease progression or death due to any cause (assessed up to approximately 2.5 years)]

      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.

    12. Percentage of Participants With Disease Progression (According to Investigator as Per Lugano Classification, Using PET or CT Scan) or Death [Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)]

      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.

    13. Progression-Free Survival (PFS) According to Investigator as Per Lugano Classification, Using PET or CT Scan [Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)]

      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.

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

      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.

    15. Event-Free Survival (EFS) According to Investigator as Per Lugano Classification, Using PET or CT Scan [Baseline until disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first (assessed up to approximately 2.5 years)]

      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.

    16. Percentage of Participants Who Died Due to Any Cause [Baseline until death due to any cause (assessed up to approximately 2.5 years]

    17. Overall Survival (OS) [Baseline until death due to any cause (assessed up to approximately 2.5 years)]

      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.

    18. Apparent Clearance (CL) of Venetoclax [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)]

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

    19. Apparent Volume of Distribution (Vd) of Venetoclax [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)]

      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.

    20. Time to Maximum Plasma Concentration (Tmax) of Venetoclax [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)]

    21. Maximum Plasma Concentration (Cmax) of Venetoclax [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)]

    22. Area Under the Plasma Concentration-Time Curve From Time 0 to Last Observed Concentration (AUClast) of Venetoclax [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)]

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

    23. Area Under the Plasma Concentration-Time Curve From Time 0 to 8 Hours Post Dose (AUC0-8h) of Venetoclax [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)]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Participants must have histologically confirmed follicular lymphoma (FL) of Grade 1, 2, or 3a

    • Participants must have received at least one prior therapy for FL

    • For participants potentially receiving chemotherapy: if the participant has received prior bendamustine, response duration must have been greater than (>) 1 year

    • At least one bi-dimensionally measurable lesion on imaging scan defined as >1.5 centimeters (cm) in its longest dimension

    • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

    • Adequate hematologic function

    • For female participants of childbearing potential and male participants with female partners of childbearing potential, agreement to use one highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception throughout the course of study treatment and for at least 30 days after the last dose of venetoclax and 12 months after the last dose of rituximab, whichever is longer

    • Confirmed availability of archival or freshly biopsied tumor tissue meeting protocol-defined specifications prior to study enrollment

    Exclusion Criteria:

    • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products

    • Contraindication to potential treatment agents

    • Ongoing corticosteroid use >30 milligrams per day (mg/day) of prednisone or equivalent. Participants receiving corticosteroid treatment with less than equal to (</=) 30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks duration prior to randomization (Cycle 1 Day 1)

    • Primary central nervous system (CNS) lymphoma

    • Vaccination with live vaccines within 28 days prior to treatment

    • Chemotherapy or other investigational therapy within five half-lives of a biologic agent with a minimum of 28 days prior to the start of Cycle 1

    • History of other malignancy that could affect compliance with the protocol or interpretation of results

    • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the participant

    • Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)

    • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1 Day 1

    • Requires the use of warfarin

    • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis

    • Presence of positive test results for hepatitis B surface antigen or hepatitis C virus (HCV) antibody

    • Participants who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation

    • Participants with occult or prior hepatitis B virus (HBV) infection may be included if HBV deoxyribonucleic acid (DNA) is undetectable at screening. These participants must be willing to undergo monthly HBV DNA test until at least 12 months after the last treatment cycle

    • Known infection with human immunodeficiency virus (HIV) or human T-cell leukemia virus 1 (HTLV-1)

    • Pregnant or lactating

    • Recent major surgery (within 6 weeks before the start of Cycle 1 Day 1), other than for diagnosis

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Southern Cancer Center, PC Mobile Alabama United States 36608
    2 Arizona Cancer Center Tucson Arizona United States 85719
    3 UCLA School of Medicine; Hematology/Oncology Los Angeles California United States 90095
    4 Nothwest Georgia Oncology Centers P.C Austell Georgia United States 30106
    5 Northwestern University Chicago Illinois United States 60611
    6 University of Illinois at Chicago College of Medicine Chicago Illinois United States 60612-7302
    7 Primary Healthcare Associates SC - Harvey Harvey Illinois United States 60426
    8 University of Kansas; Medical Center & Medical pavilion Westwood Kansas United States 66205
    9 Sidney Kimmel Comp Cancer Ctr Baltimore Maryland United States 21231-1000
    10 Hackensack University Medical Center Hackensack New Jersey United States 07601
    11 James P. Wilmot Cancer Center Rochester New York United States 14642
    12 University of Pennsylvania; School of Medicine Philadelphia Pennsylvania United States 19104
    13 Allegheny General Hospital Pittsburgh Pennsylvania United States 15212
    14 University of Pittsburgh Pittsburgh Pennsylvania United States 15213
    15 University of Virginia Charlottesville Virginia United States 22903
    16 VCU Massey Cancer Center Richmond Virginia United States 23298-003
    17 West Virginia Uni Med. Center - Robert Byrd Health Science Morgantown West Virginia United States 26506
    18 Royal Prince Alfred Hospital; Medical Oncology Camperdown New South Wales Australia 2050
    19 St George Hospital Kogarah, New South Wales New South Wales Australia 2217
    20 Royal North Shore Hospital St. Leonards New South Wales Australia 2065
    21 Westmead Hospital; Haematology Sydney New South Wales Australia 2145
    22 Calvary Mater Newcastle Waratah New South Wales Australia 2298
    23 Townsville General Hospital Douglas Queensland Australia 4184
    24 Princess Alexandra Hospital Woolloongabba Queensland Australia 4102
    25 Queen Elizabeth Hospital; Haematology Woodville South South Australia Australia 5011
    26 Royal Hobart Hospital Hobart Tasmania Australia 7000
    27 Monash Medical Centre Clayton Victoria Australia 3168
    28 ZNA Stuivenberg Antwerpen Belgium 2060
    29 AZ Sint Jan Brugge Belgium 8000
    30 Cliniques Universitaires St-Luc Bruxelles Belgium 1200
    31 Cross Cancer Institute Edmonton Alberta Canada T6G 1Z2
    32 British Columbia Cancer Agency Kelowna British Columbia Canada V1Y 5L3
    33 University Health Network; Princess Margaret Hospital; Medical Oncology Dept Toronto Ontario Canada M5G 2M9
    34 Hopital Maisonneuve- Rosemont; Oncology Montreal Quebec Canada H1T 2M4
    35 Chum Hopital Notre Dame; Centre D'Oncologie Montreal Quebec Canada H2L 4M1
    36 Jewish General Hospital Montreal Quebec Canada H3T 1E2
    37 Saskatoon Cancer Centre; Uni of Saskatoon Campus Saskatoon Saskatchewan Canada S7N 4H4
    38 Institut de Cancerologie de l'Ouest Angers France 49933
    39 CHU Clermont Ferrand - Hôpital d'Estaing Clermont Ferrand cedex 1 France 63003
    40 Hopital Henri Mondor Creteil France 94010
    41 CHU de Dijon - Hopital le Bocage Dijon France 21000
    42 Centre Jean Bernard Le Mans France 72015
    43 CHU Montpellier Montpellier France 34295
    44 Centre Hospitalier Lyon Sud; Hematolgie Pierre Benite France 69495
    45 Klinikum Chemnitz gGmbH; Klinik f. Innere Medizin III Chemnitz Germany 09116
    46 Städtisches Klinikum Dessau Dessau-Roßlau Germany 06847
    47 BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie Dresden Germany 01307
    48 Universitätsklinik Essen; Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie Essen Germany 45122
    49 Universitätsklinikum Jena; Klinik für Innere Medizin II Jena Germany 07747
    50 Universitätsklinikum Köln; Klinik I für Innere Medizin Koeln Germany 50937
    51 Universitätsklinikum Schleswig-Holstein / Campus Lübeck, Med. Klinik I, Hämatologie/Onkologie Lübeck Germany 23562
    52 Uni. der Johannes Gutenberg-Universitaet Mainz; III. Medizinische Klinik und Poliklinik Mainz Germany 55131
    53 Universitätsklinikum Ulm; Apotheke Ulm Germany 89075
    54 Universitätsklinikum Würzburg; Medizinische Klinik und Poliklinik II; Hämatologie / Onkologie Würzburg Germany 97080
    55 A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna Bologna Emilia-Romagna Italy 40138
    56 IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica Meldola Emilia-Romagna Italy 47014
    57 Ospedale di Ravenna Ravenna Emilia-Romagna Italy 48100
    58 Ospedale Infermi di Rimini Rimini Emilia-Romagna Italy 47900
    59 Asst Papa Giovanni XXIII Bergamo Lombardia Italy 24100
    60 Ospedale Niguarda Milano Milano Lombardia Italy 20162
    61 Irccs Policlinico San Matteo; Divisione Di Ematologia Pavia Lombardia Italy 27100
    62 Azienda Ospedale San Giovanni Torino Piemonte Italy 10126
    63 Az. Osp. Di Careggi; Divisione Di Ematologia Firenze Toscana Italy 50135
    64 Blackpool Victoria Hospital Blackpool United Kingdom FY3 8NR
    65 St James University Hospital Leeds United Kingdom LS9 7TF
    66 Leicester Royal Infirmary; Dept. of Medical Oncology Leicester United Kingdom LE1 5WW
    67 University College London, Department of Haematology London United Kingdom NW1 2PG
    68 Royal Marsden Nhs Trust; Consultant Cancer Physician London United Kingdom SW3 6JJ
    69 Christie Hospital; Breast Cancer Research Office Manchester United Kingdom M20 4QL
    70 Churchill Hospital; Oxford Cancer and Haematology Centre Oxford United Kingdom OX3 7LJ
    71 Royal Marsden NHS Foundation Trust Sutton United Kingdom SM2 5PT

    Sponsors and Collaborators

    • Hoffmann-La Roche
    • AbbVie

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT02187861
    Other Study ID Numbers:
    • BO29337
    • 2014-000576-26
    First Posted:
    Jul 11, 2014
    Last Update Posted:
    Jun 5, 2019
    Last Verified:
    Jun 1, 2019
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, Follicular
    Lymphoma, Non-Hodgkin
    Rituximab
    Bendamustine Hydrochloride
    Venetoclax

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Period Title: Overall Study
    STARTED 9 52 51 51
    Treated 9 52 49 50
    COMPLETED 3 4 19 19
    NOT COMPLETED 6 48 32 32

    Baseline Characteristics

    Arm/Group Title 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
    Arm/Group 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. 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. 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. 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. Total of all reporting groups
    Overall Participants 9 52 51 51 163
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    57.9
    (12.7)
    61.9
    (12.0)
    64.9
    (9.8)
    61.0
    (11.6)
    62.3
    (11.3)
    Sex: Female, Male (Count of Participants)
    Female
    5
    55.6%
    25
    48.1%
    16
    31.4%
    21
    41.2%
    67
    41.1%
    Male
    4
    44.4%
    27
    51.9%
    35
    68.6%
    30
    58.8%
    96
    58.9%

    Outcome Measures

    1. Primary Outcome
    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)
    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.
    Time Frame 6-8 weeks after Cycle 6 Day 1 (PRA) (Cycle length = 28 days)

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    Number (95% Confidence Interval) [percentage of participants]
    55.6
    617.8%
    11.5
    22.1%
    74.5
    146.1%
    70.6
    138.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR), Chemotherapy-Containing Cohort: Arm C (BR)
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in response rates
    Estimated Value 3.92
    Confidence Interval (2-Sided) 95%
    -13.38 to 21.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Participants With CMR According to Investigator as Per Lugano Classification, Using PET Scan at PRA
    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.
    Time Frame 4-10 weeks after Cycle 6 Day 1 (Cycle length = 28 days)

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    Number (95% Confidence Interval) [percentage of participants]
    55.6
    617.8%
    15.4
    29.6%
    70.6
    138.4%
    68.6
    134.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR), Chemotherapy-Containing Cohort: Arm C (BR)
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in response rates
    Estimated Value 1.96
    Confidence Interval (2-Sided) 95%
    -15.89 to 19.81
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Percentage of Participants With CMR According to IRC as Per Lugano Classification, Using PET Scan at Year 1
    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.
    Time Frame 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    Number (95% Confidence Interval) [percentage of participants]
    55.6
    617.8%
    21.2
    40.8%
    41.2
    80.8%
    39.2
    76.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR), Chemotherapy-Containing Cohort: Arm C (BR)
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in response rates
    Estimated Value 1.96
    Confidence Interval (2-Sided) 95%
    -17.07 to 20.99
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Percentage of Participants With CMR According to Investigator as Per Lugano Classification, Using PET Scan at Year 1
    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.
    Time Frame 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    Number (95% Confidence Interval) [percentage of participants]
    55.6
    617.8%
    17.3
    33.3%
    39.2
    76.9%
    47.1
    92.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR), Chemotherapy-Containing Cohort: Arm C (BR)
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in response rates
    Estimated Value -7.84
    Confidence Interval (2-Sided) 95%
    -27.01 to 11.32
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Percentage of Participants With Complete Response (CR) According to IRC as Per Lugano Classification, Using Computed Tomography (CT) Scan
    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.
    Time Frame 6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    6-8 weeks after Cycle 6 Day 1
    44.4
    493.3%
    5.7
    11%
    39.2
    76.9%
    25.5
    50%
    Year 1
    55.6
    617.8%
    13.2
    25.4%
    27.5
    53.9%
    23.5
    46.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR), Chemotherapy-Containing Cohort: Arm C (BR)
    Comments At 6-8 weeks after Cycle 6 Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in response rates
    Estimated Value 13.73
    Confidence Interval (2-Sided) 95%
    -4.24 to 31.69
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR), Chemotherapy-Containing Cohort: Arm C (BR)
    Comments At Year 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in response rates
    Estimated Value 3.92
    Confidence Interval (2-Sided) 95%
    -12.98 to 20.82
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Percentage of Participants With CR According to Investigator as Per Lugano Classification, Using CT Scan
    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.
    Time Frame 4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    4-10 weeks after Cycle 6 Day 1
    22.2
    246.7%
    5.7
    11%
    15.7
    30.8%
    31.4
    61.6%
    Year 1
    33.3
    370%
    5.7
    11%
    13.7
    26.9%
    21.6
    42.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR), Chemotherapy-Containing Cohort: Arm C (BR)
    Comments At 4-10 weeks after Cycle 6 Day 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in response rates
    Estimated Value -15.69
    Confidence Interval (2-Sided) 95%
    -31.87 to 0.49
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR), Chemotherapy-Containing Cohort: Arm C (BR)
    Comments At Year 1
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Difference in response rates
    Estimated Value -7.84
    Confidence Interval (2-Sided) 95%
    -22.56 to 6.87
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Percentage of Participants With Objective Response (OR) According to IRC as Per Lugano Classification, Using PET Scan
    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.
    Time Frame 6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    6-8 weeks after Cycle 6 Day 1
    55.6
    617.8%
    21.2
    40.8%
    76.5
    150%
    74.5
    146.1%
    Year 1
    66.7
    741.1%
    32.7
    62.9%
    45.1
    88.4%
    51.0
    100%
    8. Secondary Outcome
    Title Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using PET Scan
    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.
    Time Frame 4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    4-10 weeks after Cycle 6 Day 1
    55.6
    617.8%
    28.8
    55.4%
    76.5
    150%
    76.5
    150%
    Year 1
    55.6
    617.8%
    21.2
    40.8%
    39.2
    76.9%
    49.0
    96.1%
    9. Secondary Outcome
    Title Percentage of Participants With OR According to IRC as Per Lugano Classification, Using CT Scan
    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.
    Time Frame 6-8 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    6-8 weeks after Cycle 6 Day 1
    66.7
    741.1%
    30.2
    58.1%
    80.4
    157.6%
    84.3
    165.3%
    Year 1
    66.7
    741.1%
    22.6
    43.5%
    41.2
    80.8%
    60.8
    119.2%
    10. Secondary Outcome
    Title Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using CT Scan
    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.
    Time Frame 4-10 weeks after Cycle 6 Day 1 and 48-56 weeks after Cycle 1 Day 1 (Cycle length = 28 days)

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    4-10 weeks after Cycle 6 Day 1
    55.6
    617.8%
    32.1
    61.7%
    74.5
    146.1%
    78.4
    153.7%
    Year 1
    55.6
    617.8%
    28.3
    54.4%
    47.1
    92.4%
    49.0
    96.1%
    11. Secondary Outcome
    Title Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using PET or CT Scan
    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).
    Time Frame Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)

    Outcome Measure Data

    Analysis Population Description
    ITT population. 'Overall number of participants analyzed'=those evaluable for this outcome measure.
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    Number (95% Confidence Interval) [percentage of participants]
    66.7
    741.1%
    36.5
    70.2%
    80.4
    157.6%
    80.4
    157.6%
    12. Secondary Outcome
    Title Duration of Response (DOR) According to Investigator as Per Lugano Classification, Using PET or CT Scan
    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.
    Time Frame From CMR or PMR until disease progression or death due to any cause (assessed up to approximately 2.5 years)

    Outcome Measure Data

    Analysis Population Description
    ITT population. 'Overall number of participants analyzed'=those evaluable for this outcome measure.
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 25 47 47
    Median (95% Confidence Interval) [months]
    32.46
    15.79
    24.87
    15.64
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR), Chemotherapy-Containing Cohort: Arm C (BR)
    Comments Stratified Analysis: Strata were disease burden and DOR of prior cancer therapy.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.69
    Confidence Interval (2-Sided) 95%
    0.38 to 1.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments HR was calculated using Cox regression.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR), Chemotherapy-Containing Cohort: Arm C (BR)
    Comments Unstratified Analysis
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.78
    Confidence Interval (2-Sided) 95%
    0.43 to 1.40
    Parameter Dispersion Type:
    Value:
    Estimation Comments HR was calculated using Cox regression.
    13. Secondary Outcome
    Title Percentage of Participants With Disease Progression (According to Investigator as Per Lugano Classification, Using PET or CT Scan) or Death
    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.
    Time Frame Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    Number [percentage of participants]
    44.4
    493.3%
    86.5
    166.3%
    41.2
    80.8%
    52.9
    103.7%
    14. Secondary Outcome
    Title Progression-Free Survival (PFS) According to Investigator as Per Lugano Classification, Using PET or CT Scan
    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.
    Time Frame Baseline until disease progression or death due to any cause (assessed up to approximately 2.5 years)

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    Median (95% Confidence Interval) [months]
    35.09
    6.57
    27.63
    18.43
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR), Chemotherapy-Containing Cohort: Arm C (BR)
    Comments Stratified Analysis: Strata were disease burden and PFS of prior cancer therapy.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.69
    Confidence Interval (2-Sided) 95%
    0.38 to 1.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments HR was calculated using Cox regression.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR), Chemotherapy-Containing Cohort: Arm C (BR)
    Comments Unstratified Analysis
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.77
    Confidence Interval (2-Sided) 95%
    0.43 to 1.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments HR was calculated using Cox regression.
    15. Secondary Outcome
    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
    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.
    Time Frame Baseline until disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first (assessed up to approximately 2.5 years)

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    Number [percentage of participants]
    44.4
    493.3%
    86.5
    166.3%
    41.2
    80.8%
    52.9
    103.7%
    16. Secondary Outcome
    Title Event-Free Survival (EFS) According to Investigator as Per Lugano Classification, Using PET or CT Scan
    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.
    Time Frame Baseline until disease progression, death, or start of a new anti-lymphoma therapy whichever occurred first (assessed up to approximately 2.5 years)

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    Median (95% Confidence Interval) [months]
    35.09
    6.57
    27.63
    18.43
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR), Chemotherapy-Containing Cohort: Arm C (BR)
    Comments Stratified Analysis: Strata were disease burden and EFS of prior cancer therapy.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.69
    Confidence Interval (2-Sided) 95%
    0.38 to 1.24
    Parameter Dispersion Type:
    Value:
    Estimation Comments HR was calculated using Cox regression.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR), Chemotherapy-Containing Cohort: Arm C (BR)
    Comments Unstratified Analysis
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.77
    Confidence Interval (2-Sided) 95%
    0.43 to 1.36
    Parameter Dispersion Type:
    Value:
    Estimation Comments HR was calculated using Cox regression.
    17. Secondary Outcome
    Title Percentage of Participants Who Died Due to Any Cause
    Description
    Time Frame Baseline until death due to any cause (assessed up to approximately 2.5 years

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    Number [percentage of participants]
    0
    0%
    5.8
    11.2%
    2.0
    3.9%
    3.9
    7.6%
    18. Secondary Outcome
    Title Overall Survival (OS)
    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.
    Time Frame Baseline until death due to any cause (assessed up to approximately 2.5 years)

    Outcome Measure Data

    Analysis Population Description
    ITT population
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    Measure Participants 9 52 51 51
    Median (95% Confidence Interval) [months]
    NA
    NA
    NA
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR), Chemotherapy-Containing Cohort: Arm C (BR)
    Comments Stratified Analysis: Strata were disease burden and OS of prior cancer therapy.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.48
    Confidence Interval (2-Sided) 95%
    0.04 to 5.37
    Parameter Dispersion Type:
    Value:
    Estimation Comments HR was calculated using Cox regression.
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR), Chemotherapy-Containing Cohort: Arm C (BR)
    Comments Unstratified Analysis
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.51
    Confidence Interval (2-Sided) 95%
    0.05 to 5.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments HR was calculated using Cox regression.
    19. Secondary Outcome
    Title Apparent Clearance (CL) of Venetoclax
    Description CL is a quantitative measure of the rate at which a drug substance is removed from the body.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The data could not be collected as the timepoints for pharmacokinetics collection and the daily dosing of venetoclax did not permit an assessment of CL.
    Arm/Group Title Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)
    Arm/Group 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. 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. 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.
    Measure Participants 0 0 0
    20. Secondary Outcome
    Title Apparent Volume of Distribution (Vd) of Venetoclax
    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.
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    The data could not be collected as the timepoints for pharmacokinetics collection and the daily dosing of venetoclax did not permit an assessment of Vd.
    Arm/Group Title Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)
    Arm/Group 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. 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. 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.
    Measure Participants 0 0 0
    21. Secondary Outcome
    Title Time to Maximum Plasma Concentration (Tmax) of Venetoclax
    Description
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic-evaluable population included all enrolled participants with available pharmacokinetic data for venetoclax.
    Arm/Group Title Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)
    Arm/Group 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. 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. 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.
    Measure Participants 9 51 46
    Median (Full Range) [hours]
    8.00
    6.00
    6.21
    22. Secondary Outcome
    Title Maximum Plasma Concentration (Cmax) of Venetoclax
    Description
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic-evaluable population
    Arm/Group Title Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)
    Arm/Group 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. 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. 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.
    Measure Participants 9 51 46
    Mean (Standard Deviation) [nanograms per milliliter (ng/mL)]
    1350
    (427)
    1220
    (478)
    1340
    (460)
    23. Secondary Outcome
    Title Area Under the Plasma Concentration-Time Curve From Time 0 to Last Observed Concentration (AUClast) of Venetoclax
    Description Area under the plasma concentration versus time curve from zero to the last measured concentration (AUClast).
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic-evaluable population
    Arm/Group Title Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)
    Arm/Group 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. 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. 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.
    Measure Participants 9 51 46
    Mean (Standard Deviation) [hours*ng/mL]
    5310
    (1730)
    4950
    (1950)
    5500
    (2270)
    24. Secondary Outcome
    Title Area Under the Plasma Concentration-Time Curve From Time 0 to 8 Hours Post Dose (AUC0-8h) of Venetoclax
    Description Area under the plasma concentration versus time curve from time 0 (pre-dose) to 8 hours post dose (AUC0-8h).
    Time Frame 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)

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic-evaluable population. 'Overall number of participants analyzed'=those evaluable for this outcome measure.
    Arm/Group Title Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR) Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab) Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR)
    Arm/Group 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. 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. 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.
    Measure Participants 6 30 23
    Mean (Standard Deviation) [hours*ng/mL]
    5240
    (1860)
    4820
    (1980)
    5330
    (2270)

    Adverse Events

    Time Frame Baseline up to approximately 2.5 years
    Adverse Event Reporting Description Safety-evaluable population included participants who received at least one dose of any study treatment.
    Arm/Group Title 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)
    Arm/Group 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. 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. 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. 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.
    All Cause Mortality
    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)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    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)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/9 (44.4%) 16/52 (30.8%) 26/49 (53.1%) 12/50 (24%)
    Blood and lymphatic system disorders
    Anaemia 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Aplastic anaemia 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Febrile neutropenia 1/9 (11.1%) 0/52 (0%) 6/49 (12.2%) 3/50 (6%)
    Thrombocytopenia 1/9 (11.1%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    NEUTROPENIA 1/9 (11.1%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Cardiac disorders
    Acute left ventricular failure 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    Cardiac failure 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Myocardial infarction 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    ACUTE CORONARY SYNDROME 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    LEFT VENTRICULAR FAILURE 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    ATRIAL FIBRILLATION 0/9 (0%) 0/52 (0%) 0/49 (0%) 1/50 (2%)
    Eye disorders
    Diplopia 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Colitis 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    Erosive oesophagitis 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Pancreatitis 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    Vomiting 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    General disorders
    Pyrexia 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Hepatobiliary disorders
    Cholecystitis chronic 0/9 (0%) 0/52 (0%) 0/49 (0%) 1/50 (2%)
    Cholelithiasis 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Immune system disorders
    Cytokine release syndrome 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Infections and infestations
    Acute sinusitis 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Atypical pneumonia 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    Bronchitis 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Cellulitis 0/9 (0%) 0/52 (0%) 0/49 (0%) 2/50 (4%)
    Clostridium difficile colitis 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Cystitis 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    Cytomegalovirus infection 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Device related infection 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    Diverticulitis 0/9 (0%) 0/52 (0%) 0/49 (0%) 1/50 (2%)
    Herpes zoster disseminated 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    Lower respiratory tract infection 0/9 (0%) 1/52 (1.9%) 1/49 (2%) 0/50 (0%)
    Lung infection 0/9 (0%) 0/52 (0%) 2/49 (4.1%) 1/50 (2%)
    Oesophageal candidiasis 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Pneumocystis jirovecii pneumonia 0/9 (0%) 0/52 (0%) 3/49 (6.1%) 0/50 (0%)
    Pneumonia 0/9 (0%) 2/52 (3.8%) 3/49 (6.1%) 1/50 (2%)
    Pneumonia pseudomonal 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Pyelonephritis 0/9 (0%) 0/52 (0%) 0/49 (0%) 1/50 (2%)
    Respiratory syncytial virus infection 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Sepsis 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Sinusitis 0/9 (0%) 1/52 (1.9%) 1/49 (2%) 0/50 (0%)
    Skin infection 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Viral infection 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    HERPES SIMPLEX 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Injury, poisoning and procedural complications
    Fall 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Investigations
    Blood creatine phosphokinase increased 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Blood lactate dehydrogenase increased 0/9 (0%) 2/52 (3.8%) 0/49 (0%) 0/50 (0%)
    Metabolism and nutrition disorders
    Dehydration 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Tumour lysis syndrome 0/9 (0%) 1/52 (1.9%) 1/49 (2%) 1/50 (2%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    Myelodysplastic syndrome 1/9 (11.1%) 0/52 (0%) 3/49 (6.1%) 0/50 (0%)
    Squamous cell carcinoma of skin 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    LUNG ADENOCARCINOMA 0/9 (0%) 0/52 (0%) 0/49 (0%) 1/50 (2%)
    METASTATIC MALIGNANT MELANOMA 0/9 (0%) 0/52 (0%) 0/49 (0%) 1/50 (2%)
    Nervous system disorders
    Dizziness 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Syncope 1/9 (11.1%) 0/52 (0%) 1/49 (2%) 1/50 (2%)
    Psychiatric disorders
    Depression 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    Renal colic 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Dyspnoea 0/9 (0%) 0/52 (0%) 0/49 (0%) 2/50 (4%)
    Hypoxia 0/9 (0%) 0/52 (0%) 1/49 (2%) 1/50 (2%)
    Pleuritic pain 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    Pulmonary embolism 0/9 (0%) 0/52 (0%) 0/49 (0%) 1/50 (2%)
    Pulmonary haemorrhage 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    Skin and subcutaneous tissue disorders
    Urticaria 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Surgical and medical procedures
    Renal stone removal 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Vascular disorders
    Embolism 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Haemorrhage 0/9 (0%) 1/52 (1.9%) 0/49 (0%) 0/50 (0%)
    Hypotension 0/9 (0%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Other (Not Including 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)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/9 (100%) 49/52 (94.2%) 49/49 (100%) 48/50 (96%)
    Blood and lymphatic system disorders
    Anaemia 2/9 (22.2%) 3/52 (5.8%) 19/49 (38.8%) 8/50 (16%)
    Leukopenia 2/9 (22.2%) 5/52 (9.6%) 6/49 (12.2%) 3/50 (6%)
    Neutropenia 5/9 (55.6%) 14/52 (26.9%) 30/49 (61.2%) 17/50 (34%)
    Thrombocytopenia 3/9 (33.3%) 7/52 (13.5%) 28/49 (57.1%) 8/50 (16%)
    Cardiac disorders
    Atrial fibrillation 1/9 (11.1%) 2/52 (3.8%) 2/49 (4.1%) 0/50 (0%)
    Palpitations 2/9 (22.2%) 0/52 (0%) 0/49 (0%) 1/50 (2%)
    Sinus tachycardia 0/9 (0%) 2/52 (3.8%) 3/49 (6.1%) 1/50 (2%)
    Tachycardia 0/9 (0%) 1/52 (1.9%) 3/49 (6.1%) 0/50 (0%)
    Eye disorders
    Vision blurred 1/9 (11.1%) 1/52 (1.9%) 1/49 (2%) 0/50 (0%)
    Gastrointestinal disorders
    Abdominal discomfort 1/9 (11.1%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Abdominal distension 0/9 (0%) 5/52 (9.6%) 0/49 (0%) 1/50 (2%)
    Abdominal pain 2/9 (22.2%) 6/52 (11.5%) 6/49 (12.2%) 5/50 (10%)
    Abdominal pain upper 1/9 (11.1%) 2/52 (3.8%) 3/49 (6.1%) 3/50 (6%)
    Constipation 3/9 (33.3%) 5/52 (9.6%) 10/49 (20.4%) 17/50 (34%)
    Diarrhoea 5/9 (55.6%) 21/52 (40.4%) 24/49 (49%) 14/50 (28%)
    Dyspepsia 2/9 (22.2%) 3/52 (5.8%) 0/49 (0%) 2/50 (4%)
    Dysphagia 1/9 (11.1%) 3/52 (5.8%) 1/49 (2%) 1/50 (2%)
    Large intestine polyp 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Mouth ulceration 1/9 (11.1%) 0/52 (0%) 3/49 (6.1%) 2/50 (4%)
    Nausea 7/9 (77.8%) 14/52 (26.9%) 32/49 (65.3%) 23/50 (46%)
    Stomatitis 0/9 (0%) 0/52 (0%) 5/49 (10.2%) 1/50 (2%)
    Vomiting 4/9 (44.4%) 7/52 (13.5%) 23/49 (46.9%) 13/50 (26%)
    General disorders
    Asthenia 1/9 (11.1%) 4/52 (7.7%) 5/49 (10.2%) 4/50 (8%)
    Catheter site pain 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Chills 1/9 (11.1%) 5/52 (9.6%) 3/49 (6.1%) 2/50 (4%)
    Fatigue 3/9 (33.3%) 13/52 (25%) 21/49 (42.9%) 15/50 (30%)
    Influenza like illness 2/9 (22.2%) 1/52 (1.9%) 2/49 (4.1%) 2/50 (4%)
    Malaise 0/9 (0%) 1/52 (1.9%) 3/49 (6.1%) 0/50 (0%)
    Mass 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 1/50 (2%)
    Peripheral swelling 1/9 (11.1%) 1/52 (1.9%) 2/49 (4.1%) 0/50 (0%)
    Pyrexia 1/9 (11.1%) 5/52 (9.6%) 10/49 (20.4%) 9/50 (18%)
    OEDEMA PERIPHERAL 0/9 (0%) 1/52 (1.9%) 1/49 (2%) 3/50 (6%)
    Immune system disorders
    HYPOGAMMAGLOBULINAEMIA 0/9 (0%) 0/52 (0%) 4/49 (8.2%) 2/50 (4%)
    Infections and infestations
    Aspergillus infection 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Bronchitis 0/9 (0%) 2/52 (3.8%) 6/49 (12.2%) 1/50 (2%)
    Cellulitis 1/9 (11.1%) 1/52 (1.9%) 0/49 (0%) 2/50 (4%)
    Conjunctivitis 0/9 (0%) 0/52 (0%) 0/49 (0%) 4/50 (8%)
    Herpes zoster 1/9 (11.1%) 1/52 (1.9%) 2/49 (4.1%) 1/50 (2%)
    Lower respiratory tract infection 0/9 (0%) 2/52 (3.8%) 3/49 (6.1%) 0/50 (0%)
    Lung infection 0/9 (0%) 0/52 (0%) 4/49 (8.2%) 0/50 (0%)
    Mycobacterium kansasii infection 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Nasopharyngitis 3/9 (33.3%) 4/52 (7.7%) 1/49 (2%) 0/50 (0%)
    Oral candidiasis 1/9 (11.1%) 0/52 (0%) 4/49 (8.2%) 2/50 (4%)
    Oral herpes 0/9 (0%) 0/52 (0%) 3/49 (6.1%) 1/50 (2%)
    Perineal abscess 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Rhinitis 0/9 (0%) 0/52 (0%) 1/49 (2%) 4/50 (8%)
    Sinusitis 1/9 (11.1%) 3/52 (5.8%) 3/49 (6.1%) 4/50 (8%)
    Upper respiratory tract infection 2/9 (22.2%) 6/52 (11.5%) 6/49 (12.2%) 4/50 (8%)
    Urinary tract infection 1/9 (11.1%) 4/52 (7.7%) 5/49 (10.2%) 2/50 (4%)
    SUBCUTANEOUS ABSCESS 1/9 (11.1%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    PNEUMONIA 1/9 (11.1%) 0/52 (0%) 4/49 (8.2%) 2/50 (4%)
    Injury, poisoning and procedural complications
    Infusion related reaction 2/9 (22.2%) 18/52 (34.6%) 10/49 (20.4%) 7/50 (14%)
    Laceration 1/9 (11.1%) 0/52 (0%) 1/49 (2%) 0/50 (0%)
    Limb injury 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Investigations
    Aspartate aminotransferase increased 0/9 (0%) 0/52 (0%) 5/49 (10.2%) 2/50 (4%)
    Blood alkaline phosphatase increased 1/9 (11.1%) 0/52 (0%) 2/49 (4.1%) 3/50 (6%)
    Blood creatinine increased 0/9 (0%) 3/52 (5.8%) 2/49 (4.1%) 0/50 (0%)
    Gamma-glutamyltransferase increased 0/9 (0%) 0/52 (0%) 0/49 (0%) 5/50 (10%)
    Weight decreased 1/9 (11.1%) 4/52 (7.7%) 8/49 (16.3%) 0/50 (0%)
    Weight increased 0/9 (0%) 3/52 (5.8%) 2/49 (4.1%) 0/50 (0%)
    White blood cell count decreased 0/9 (0%) 0/52 (0%) 4/49 (8.2%) 1/50 (2%)
    Metabolism and nutrition disorders
    Decreased appetite 0/9 (0%) 5/52 (9.6%) 10/49 (20.4%) 7/50 (14%)
    Hyperglycaemia 0/9 (0%) 2/52 (3.8%) 3/49 (6.1%) 1/50 (2%)
    Hypokalaemia 1/9 (11.1%) 6/52 (11.5%) 13/49 (26.5%) 4/50 (8%)
    Hypomagnesaemia 0/9 (0%) 1/52 (1.9%) 6/49 (12.2%) 0/50 (0%)
    Hyponatraemia 0/9 (0%) 0/52 (0%) 3/49 (6.1%) 0/50 (0%)
    Hypophosphataemia 0/9 (0%) 3/52 (5.8%) 5/49 (10.2%) 1/50 (2%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/9 (11.1%) 3/52 (5.8%) 5/49 (10.2%) 2/50 (4%)
    Back pain 3/9 (33.3%) 2/52 (3.8%) 0/49 (0%) 7/50 (14%)
    Joint swelling 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Musculoskeletal pain 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Musculoskeletal stiffness 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Myalgia 0/9 (0%) 2/52 (3.8%) 4/49 (8.2%) 1/50 (2%)
    Periarthritis 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BASAL CELL CARCINOMA 0/9 (0%) 1/52 (1.9%) 1/49 (2%) 3/50 (6%)
    COLON ADENOMA 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Nervous system disorders
    Burning sensation 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Dizziness 1/9 (11.1%) 4/52 (7.7%) 8/49 (16.3%) 3/50 (6%)
    Dysgeusia 0/9 (0%) 3/52 (5.8%) 3/49 (6.1%) 4/50 (8%)
    Headache 3/9 (33.3%) 5/52 (9.6%) 8/49 (16.3%) 6/50 (12%)
    Peripheral sensory neuropathy 1/9 (11.1%) 1/52 (1.9%) 0/49 (0%) 1/50 (2%)
    Presyncope 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    COGNITIVE DISORDER 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Psychiatric disorders
    Anxiety 1/9 (11.1%) 2/52 (3.8%) 2/49 (4.1%) 0/50 (0%)
    Hallucination 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Insomnia 3/9 (33.3%) 1/52 (1.9%) 7/49 (14.3%) 2/50 (4%)
    Renal and urinary disorders
    Dysuria 2/9 (22.2%) 0/52 (0%) 1/49 (2%) 2/50 (4%)
    Renal colic 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 3/9 (33.3%) 6/52 (11.5%) 12/49 (24.5%) 12/50 (24%)
    Dyspnoea 1/9 (11.1%) 1/52 (1.9%) 6/49 (12.2%) 2/50 (4%)
    Lung consolidation 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Nasal congestion 0/9 (0%) 1/52 (1.9%) 2/49 (4.1%) 3/50 (6%)
    Oropharyngeal pain 1/9 (11.1%) 1/52 (1.9%) 2/49 (4.1%) 1/50 (2%)
    Productive cough 0/9 (0%) 1/52 (1.9%) 2/49 (4.1%) 5/50 (10%)
    Rhinorrhoea 0/9 (0%) 0/52 (0%) 1/49 (2%) 4/50 (8%)
    Throat irritation 1/9 (11.1%) 1/52 (1.9%) 0/49 (0%) 1/50 (2%)
    Skin and subcutaneous tissue disorders
    Erythema 1/9 (11.1%) 1/52 (1.9%) 3/49 (6.1%) 2/50 (4%)
    Pruritus 1/9 (11.1%) 3/52 (5.8%) 1/49 (2%) 4/50 (8%)
    Psoriasis 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Yellow skin 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)
    Vascular disorders
    Flushing 1/9 (11.1%) 1/52 (1.9%) 0/49 (0%) 2/50 (4%)
    Hypertension 1/9 (11.1%) 3/52 (5.8%) 1/49 (2%) 2/50 (4%)
    Hypotension 2/9 (22.2%) 2/52 (3.8%) 3/49 (6.1%) 2/50 (4%)
    Orthostatic hypotension 1/9 (11.1%) 0/52 (0%) 0/49 (0%) 0/50 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

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

    Results Point of Contact

    Name/Title Medical Communications
    Organization Hoffmann-La Roche
    Phone 800-821-8590
    Email genentech@druginfo.com
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT02187861
    Other Study ID Numbers:
    • BO29337
    • 2014-000576-26
    First Posted:
    Jul 11, 2014
    Last Update Posted:
    Jun 5, 2019
    Last Verified:
    Jun 1, 2019