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)

NCT ID: NCT02187861

Last Updated: 2019-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 163 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-01
• Study Completion Date: 2018-03-16

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.

Conditions

Follicular Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

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

Bendamustine

Intervention Type: DRUG

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

Rituximab

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

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

Rituximab

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

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

Bendamustine

Intervention Type: DRUG

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

Rituximab

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Bendamustine

Intervention Type: DRUG

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

Rituximab

Intervention Type: DRUG

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

Interventions

Venetoclax

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

Intervention Type: DRUG

Bendamustine

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

Intervention Type: DRUG

Rituximab

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

Intervention Type: DRUG

Other Intervention Names

GDC-0199; ABT-199; Levact; MabThera; Rituxan

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Southern Cancer Center, PC

Mobile, Alabama, United States

Arizona Cancer Center

Tucson, Arizona, United States

UCLA School of Medicine; Hematology/Oncology

Los Angeles, California, United States

Nothwest Georgia Oncology Centers P.C

Austell, Georgia, United States

Northwestern University

Chicago, Illinois, United States

University of Illinois at Chicago College of Medicine

Chicago, Illinois, United States

Primary Healthcare Associates SC - Harvey

Harvey, Illinois, United States

University of Kansas; Medical Center & Medical pavilion

Westwood, Kansas, United States

Sidney Kimmel Comp Cancer Ctr

Baltimore, Maryland, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

James P. Wilmot Cancer Center

Rochester, New York, United States

University of Pennsylvania; School of Medicine

Philadelphia, Pennsylvania, United States

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

University of Virginia

Charlottesville, Virginia, United States

VCU Massey Cancer Center

Richmond, Virginia, United States

West Virginia Uni Med. Center - Robert Byrd Health Science

Morgantown, West Virginia, United States

Royal Prince Alfred Hospital; Medical Oncology

Camperdown, New South Wales, Australia

St George Hospital

Kogarah, New South Wales, New South Wales, Australia

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Westmead Hospital; Haematology

Sydney, New South Wales, Australia

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Townsville General Hospital

Douglas, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Queen Elizabeth Hospital; Haematology

Woodville South, South Australia, Australia

Royal Hobart Hospital

Hobart, Tasmania, Australia

Monash Medical Centre

Clayton, Victoria, Australia

ZNA Stuivenberg

Antwerp, , Belgium

AZ Sint Jan

Bruges, , Belgium

Cliniques Universitaires St-Luc

Brussels, , Belgium

Cross Cancer Institute

Edmonton, Alberta, Canada

British Columbia Cancer Agency

Kelowna, British Columbia, Canada

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, Canada

Hopital Maisonneuve- Rosemont; Oncology

Montreal, Quebec, Canada

Chum Hopital Notre Dame; Centre D'Oncologie

Montreal, Quebec, Canada

Jewish General Hospital

Montreal, Quebec, Canada

Saskatoon Cancer Centre; Uni of Saskatoon Campus

Saskatoon, Saskatchewan, Canada

Institut de Cancerologie de l'Ouest

Angers, , France

CHU Clermont Ferrand - Hôpital d'Estaing

Clermont-Ferrand, , France

Hopital Henri Mondor

Créteil, , France

CHU de Dijon - Hopital le Bocage

Dijon, , France

Centre Jean Bernard

Le Mans, , France

CHU Montpellier

Montpellier, , France

Centre Hospitalier Lyon Sud; Hematolgie

Pierre-Bénite, , France

Klinikum Chemnitz gGmbH; Klinik f. Innere Medizin III

Chemnitz, , Germany

Universitätsklinikum Köln; Klinik I für Innere Medizin

Cologne, , Germany

Städtisches Klinikum Dessau

Dessau, , Germany

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

Dresden, , Germany

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

Essen, , Germany

Universitätsklinikum Jena; Klinik für Innere Medizin II

Jena, , Germany

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

Lübeck, , Germany

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

Mainz, , Germany

Universitätsklinikum Ulm; Apotheke

Ulm, , Germany

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

Würzburg, , Germany

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

Bologna, Emilia-Romagna, Italy

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

Meldola, Emilia-Romagna, Italy

Ospedale di Ravenna

Ravenna, Emilia-Romagna, Italy

Ospedale Infermi di Rimini

Rimini, Emilia-Romagna, Italy

Asst Papa Giovanni XXIII

Bergamo, Lombardy, Italy

Ospedale Niguarda Milano

Milan, Lombardy, Italy

Irccs Policlinico San Matteo; Divisione Di Ematologia

Pavia, Lombardy, Italy

Azienda Ospedale San Giovanni

Turin, Piedmont, Italy

Az. Osp. Di Careggi; Divisione Di Ematologia

Florence, Tuscany, Italy

Blackpool Victoria Hospital

Blackpool, , United Kingdom

St James University Hospital

Leeds, , United Kingdom

Leicester Royal Infirmary; Dept. of Medical Oncology

Leicester, , United Kingdom

University College London, Department of Haematology

London, , United Kingdom

Royal Marsden Nhs Trust; Consultant Cancer Physician

London, , United Kingdom

Christie Hospital; Breast Cancer Research Office

Manchester, , United Kingdom

Churchill Hospital; Oxford Cancer and Haematology Centre

Oxford, , United Kingdom

Royal Marsden NHS Foundation Trust

Sutton, , United Kingdom

Countries

United States; Australia; Belgium; Canada; France; Germany; Italy; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 32785666 (View on PubMed)

Other Identifiers

2014-000576-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BO29337

Identifier Type: -

Identifier Source: org_study_id