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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)

Primary Purpose

Follicular Lymphoma

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Venetoclax

Bendamustine

Rituximab

About this trial

This is an interventional treatment trial for Follicular Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Southern Cancer Center, PC
Arizona Cancer Center
UCLA School of Medicine; Hematology/Oncology
Nothwest Georgia Oncology Centers P.C
Northwestern University
University of Illinois at Chicago College of Medicine
Primary Healthcare Associates SC - Harvey
University of Kansas; Medical Center & Medical pavilion
Sidney Kimmel Comp Cancer Ctr
Hackensack University Medical Center
James P. Wilmot Cancer Center
University of Pennsylvania; School of Medicine
Allegheny General Hospital
University of Pittsburgh
University of Virginia
VCU Massey Cancer Center
West Virginia Uni Med. Center - Robert Byrd Health Science
Royal Prince Alfred Hospital; Medical Oncology
St George Hospital
Royal North Shore Hospital
Westmead Hospital; Haematology
Calvary Mater Newcastle
Townsville General Hospital
Princess Alexandra Hospital
Queen Elizabeth Hospital; Haematology
Royal Hobart Hospital
Monash Medical Centre
ZNA Stuivenberg
AZ Sint Jan
Cliniques Universitaires St-Luc
Cross Cancer Institute
British Columbia Cancer Agency
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
Hopital Maisonneuve- Rosemont; Oncology
Chum Hopital Notre Dame; Centre D'Oncologie
Jewish General Hospital
Saskatoon Cancer Centre; Uni of Saskatoon Campus
Institut de Cancerologie de l'Ouest
CHU Clermont Ferrand - Hôpital d'Estaing
Hopital Henri Mondor
CHU de Dijon - Hopital le Bocage
Centre Jean Bernard
CHU Montpellier
Centre Hospitalier Lyon Sud; Hematolgie
Klinikum Chemnitz gGmbH; Klinik f. Innere Medizin III
Städtisches Klinikum Dessau
BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie
Universitätsklinik Essen; Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
Universitätsklinikum Jena; Klinik für Innere Medizin II
Universitätsklinikum Köln; Klinik I für Innere Medizin
Universitätsklinikum Schleswig-Holstein / Campus Lübeck, Med. Klinik I, Hämatologie/Onkologie
Uni. der Johannes Gutenberg-Universitaet Mainz; III. Medizinische Klinik und Poliklinik
Universitätsklinikum Ulm; Apotheke
Universitätsklinikum Würzburg; Medizinische Klinik und Poliklinik II; Hämatologie / Onkologie
A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
Ospedale di Ravenna
Ospedale Infermi di Rimini
Asst Papa Giovanni XXIII
Ospedale Niguarda Milano
Irccs Policlinico San Matteo; Divisione Di Ematologia
Azienda Ospedale San Giovanni
Az. Osp. Di Careggi; Divisione Di Ematologia
Blackpool Victoria Hospital
St James University Hospital
Leicester Royal Infirmary; Dept. of Medical Oncology
University College London, Department of Haematology
Royal Marsden Nhs Trust; Consultant Cancer Physician
Christie Hospital; Breast Cancer Research Office
Churchill Hospital; Oxford Cancer and Haematology Centre
Royal Marsden NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Arm Label

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 Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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)

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

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

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.

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

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.

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

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

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.

Percentage of Participants With CR According to Investigator as Per Lugano Classification, Using CT Scan

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.

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

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.

Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using PET Scan

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.

Percentage of Participants With OR According to IRC as Per Lugano Classification, Using CT Scan

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.

Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using CT Scan

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.

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

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).

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

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.

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

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.

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

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.

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

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

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.

Percentage of Participants Who Died Due to Any Cause

Overall Survival (OS)

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.

Apparent Clearance (CL) of Venetoclax

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

Apparent Volume of Distribution (Vd) of Venetoclax

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 to Maximum Plasma Concentration (Tmax) of Venetoclax

Maximum Plasma Concentration (Cmax) of Venetoclax

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

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

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

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

Full Information

NCT ID

NCT02187861

First Posted

July 9, 2014

Last Updated

June 3, 2019

Sponsor

Hoffmann-La Roche

Collaborators

AbbVie

1. Study Identification

Unique Protocol Identification Number

NCT02187861

Brief Title

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)

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2019

Overall Recruitment Status

Completed

Study Start Date

December 1, 2014 (Actual)

Primary Completion Date

September 27, 2016 (Actual)

Study Completion Date

March 16, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

Collaborators

AbbVie

4. Oversight

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Follicular Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

163 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

Chemotherapy-Containing Cohort: Arm C (BR)

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Venetoclax

Other Intervention Name(s)

GDC-0199, ABT-199

Intervention Description

Venetoclax will be administered as per the schedule specified under arm description.

Intervention Type

Drug

Intervention Name(s)

Bendamustine

Other Intervention Name(s)

Levact

Intervention Description

Bendamustine will be administered as per the schedule specified under arm description.

Intervention Type

Drug

Intervention Name(s)

Rituximab

Other Intervention Name(s)

MabThera, Rituxan

Intervention Description

Rituximab will be administered as per the schedule specified under arm description.

Primary Outcome Measure Information:

Title

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

Percentage of Participants With CR According to Investigator as Per Lugano Classification, Using CT Scan

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using PET Scan

Description

Time Frame

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

Title

Percentage of Participants With OR According to IRC as Per Lugano Classification, Using CT Scan

Description

Time Frame

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

Title

Percentage of Participants With OR According to Investigator as Per Lugano Classification, Using CT Scan

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

Title

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

Description

Time Frame

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

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

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)

Title

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

Description

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)

Title

Percentage of Participants Who Died Due to Any Cause

Time Frame

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

Title

Overall Survival (OS)

Description

Time Frame

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

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)

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

Title

Time to Maximum Plasma Concentration (Tmax) of Venetoclax

Time Frame

Title

Maximum Plasma Concentration (Cmax) of Venetoclax

Time Frame

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

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

Southern Cancer Center, PC

City

Mobile

State/Province

Alabama

ZIP/Postal Code

36608

Country

United States

Facility Name

Arizona Cancer Center

City

Tucson

State/Province

Arizona

ZIP/Postal Code

85719

Country

United States

Facility Name

UCLA School of Medicine; Hematology/Oncology

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Nothwest Georgia Oncology Centers P.C

City

Austell

State/Province

Georgia

ZIP/Postal Code

30106

Country

United States

Facility Name

Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

University of Illinois at Chicago College of Medicine

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612-7302

Country

United States

Facility Name

Primary Healthcare Associates SC - Harvey

City

Harvey

State/Province

Illinois

ZIP/Postal Code

60426

Country

United States

Facility Name

University of Kansas; Medical Center & Medical pavilion

City

Westwood

State/Province

Kansas

ZIP/Postal Code

66205

Country

United States

Facility Name

Sidney Kimmel Comp Cancer Ctr

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21231-1000

Country

United States

Facility Name

Hackensack University Medical Center

City

Hackensack

State/Province

New Jersey

ZIP/Postal Code

07601

Country

United States

Facility Name

James P. Wilmot Cancer Center

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

Facility Name

University of Pennsylvania; School of Medicine

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Allegheny General Hospital

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15212

Country

United States

Facility Name

University of Pittsburgh

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

Facility Name

University of Virginia

City

Charlottesville

State/Province

Virginia

ZIP/Postal Code

22903

Country

United States

Facility Name

VCU Massey Cancer Center

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23298-003

Country

United States

Facility Name

West Virginia Uni Med. Center - Robert Byrd Health Science

City

Morgantown

State/Province

West Virginia

ZIP/Postal Code

26506

Country

United States

Facility Name

Royal Prince Alfred Hospital; Medical Oncology

City

Camperdown

State/Province

New South Wales

ZIP/Postal Code

2050

Country

Australia

Facility Name

St George Hospital

City

Kogarah, New South Wales

State/Province

New South Wales

ZIP/Postal Code

2217

Country

Australia

Facility Name

Royal North Shore Hospital

City

St. Leonards

State/Province

New South Wales

ZIP/Postal Code

2065

Country

Australia

Facility Name

Westmead Hospital; Haematology

City

Sydney

State/Province

New South Wales

ZIP/Postal Code

2145

Country

Australia

Facility Name

Calvary Mater Newcastle

City

Waratah

State/Province

New South Wales

ZIP/Postal Code

2298

Country

Australia

Facility Name

Townsville General Hospital

City

Douglas

State/Province

Queensland

ZIP/Postal Code

4184

Country

Australia

Facility Name

Princess Alexandra Hospital

City

Woolloongabba

State/Province

Queensland

ZIP/Postal Code

4102

Country

Australia

Facility Name

Queen Elizabeth Hospital; Haematology

City

Woodville South

State/Province

South Australia

ZIP/Postal Code

5011

Country

Australia

Facility Name

Royal Hobart Hospital

City

Hobart

State/Province

Tasmania

ZIP/Postal Code

7000

Country

Australia

Facility Name

Monash Medical Centre

City

Clayton

State/Province

Victoria

ZIP/Postal Code

3168

Country

Australia

Facility Name

ZNA Stuivenberg

City

Antwerpen

ZIP/Postal Code

2060

Country

Belgium

Facility Name

AZ Sint Jan

City

Brugge

ZIP/Postal Code

8000

Country

Belgium

Facility Name

Cliniques Universitaires St-Luc

City

Bruxelles

ZIP/Postal Code

1200

Country

Belgium

Facility Name

Cross Cancer Institute

City

Edmonton

State/Province

Alberta

ZIP/Postal Code

T6G 1Z2

Country

Canada

Facility Name

British Columbia Cancer Agency

City

Kelowna

State/Province

British Columbia

ZIP/Postal Code

V1Y 5L3

Country

Canada

Facility Name

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2M9

Country

Canada

Facility Name

Hopital Maisonneuve- Rosemont; Oncology

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H1T 2M4

Country

Canada

Facility Name

Chum Hopital Notre Dame; Centre D'Oncologie

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H2L 4M1

Country

Canada

Facility Name

Jewish General Hospital

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H3T 1E2

Country

Canada

Facility Name

Saskatoon Cancer Centre; Uni of Saskatoon Campus

City

Saskatoon

State/Province

Saskatchewan

ZIP/Postal Code

S7N 4H4

Country

Canada

Facility Name

Institut de Cancerologie de l'Ouest

City

Angers

ZIP/Postal Code

49933

Country

France

Facility Name

CHU Clermont Ferrand - Hôpital d'Estaing

City

Clermont Ferrand cedex 1

ZIP/Postal Code

63003

Country

France

Facility Name

Hopital Henri Mondor

City

Creteil

ZIP/Postal Code

94010

Country

France

Facility Name

CHU de Dijon - Hopital le Bocage

City

Dijon

ZIP/Postal Code

21000

Country

France

Facility Name

Centre Jean Bernard

City

Le Mans

ZIP/Postal Code

72015

Country

France

Facility Name

CHU Montpellier

City

Montpellier

ZIP/Postal Code

34295

Country

France

Facility Name

Centre Hospitalier Lyon Sud; Hematolgie

City

Pierre Benite

ZIP/Postal Code

69495

Country

France

Facility Name

Klinikum Chemnitz gGmbH; Klinik f. Innere Medizin III

City

Chemnitz

ZIP/Postal Code

09116

Country

Germany

Facility Name

Städtisches Klinikum Dessau

City

Dessau-Roßlau

ZIP/Postal Code

06847

Country

Germany

Facility Name

BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Universitätsklinik Essen; Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie

City

Essen

ZIP/Postal Code

45122

Country

Germany

Facility Name

Universitätsklinikum Jena; Klinik für Innere Medizin II

City

Jena

ZIP/Postal Code

07747

Country

Germany

Facility Name

Universitätsklinikum Köln; Klinik I für Innere Medizin

City

Koeln

ZIP/Postal Code

50937

Country

Germany

Facility Name

Universitätsklinikum Schleswig-Holstein / Campus Lübeck, Med. Klinik I, Hämatologie/Onkologie

City

Lübeck

ZIP/Postal Code

23562

Country

Germany

Facility Name

Uni. der Johannes Gutenberg-Universitaet Mainz; III. Medizinische Klinik und Poliklinik

City

Mainz

ZIP/Postal Code

55131

Country

Germany

Facility Name

Universitätsklinikum Ulm; Apotheke

City

Ulm

ZIP/Postal Code

89075

Country

Germany

Facility Name

Universitätsklinikum Würzburg; Medizinische Klinik und Poliklinik II; Hämatologie / Onkologie

City

Würzburg

ZIP/Postal Code

97080

Country

Germany

Facility Name

A.O. Universitaria Policlinico S.Orsola-Malpighi Di Bologna

City

Bologna

State/Province

Emilia-Romagna

ZIP/Postal Code

40138

Country

Italy

Facility Name

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica

City

Meldola

State/Province

Emilia-Romagna

ZIP/Postal Code

47014

Country

Italy

Facility Name

Ospedale di Ravenna

City

Ravenna

State/Province

Emilia-Romagna

ZIP/Postal Code

48100

Country

Italy

Facility Name

Ospedale Infermi di Rimini

City

Rimini

State/Province

Emilia-Romagna

ZIP/Postal Code

47900

Country

Italy

Facility Name

Asst Papa Giovanni XXIII

City

Bergamo

State/Province

Lombardia

ZIP/Postal Code

24100

Country

Italy

Facility Name

Ospedale Niguarda Milano

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20162

Country

Italy

Facility Name

Irccs Policlinico San Matteo; Divisione Di Ematologia

City

Pavia

State/Province

Lombardia

ZIP/Postal Code

27100

Country

Italy

Facility Name

Azienda Ospedale San Giovanni

City

Torino

State/Province

Piemonte

ZIP/Postal Code

10126

Country

Italy

Facility Name

Az. Osp. Di Careggi; Divisione Di Ematologia

City

Firenze

State/Province

Toscana

ZIP/Postal Code

50135

Country

Italy

Facility Name

Blackpool Victoria Hospital

City

Blackpool

ZIP/Postal Code

FY3 8NR

Country

United Kingdom

Facility Name

St James University Hospital

City

Leeds

ZIP/Postal Code

LS9 7TF

Country

United Kingdom

Facility Name

Leicester Royal Infirmary; Dept. of Medical Oncology

City

Leicester

ZIP/Postal Code

LE1 5WW

Country

United Kingdom

Facility Name

University College London, Department of Haematology

City

London

ZIP/Postal Code

NW1 2PG

Country

United Kingdom

Facility Name

Royal Marsden Nhs Trust; Consultant Cancer Physician

City

London

ZIP/Postal Code

SW3 6JJ

Country

United Kingdom

Facility Name

Christie Hospital; Breast Cancer Research Office

City

Manchester

ZIP/Postal Code

M20 4QL

Country

United Kingdom

Facility Name

Churchill Hospital; Oxford Cancer and Haematology Centre

City

Oxford

ZIP/Postal Code

OX3 7LJ

Country

United Kingdom

Facility Name

Royal Marsden NHS Foundation Trust

City

Sutton

ZIP/Postal Code

SM2 5PT

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

32785666

Citation

Zinzani PL, Flinn IW, Yuen SLS, Topp MS, Rusconi C, Fleury I, Le Du K, Arthur C, Pro B, Gritti G, Crump M, Petrich A, Samineni D, Sinha A, Punnoose EA, Szafer-Glusman E, Spielewoy N, Mobasher M, Humphrey K, Kornacker M, Hiddemann W. Venetoclax-rituximab with or without bendamustine vs bendamustine-rituximab in relapsed/refractory follicular lymphoma. Blood. 2020 Dec 3;136(23):2628-2637. doi: 10.1182/blood.2020005588.

Results Reference

derived

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