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)
Condition: Follicular Lymphoma
MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin
Intervention: Venetoclax; Bendamustine; Rituximab
Intervention description: Venetoclax will be administered as per the schedule specified under arm description.; Bendamustine will be administered as per the schedule specified under arm description.; Rituximab will be administered as per the schedule specified under arm description.
Intervention MeSH terms: Rituximab; Venetoclax; Bendamustine Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 163.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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