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)

NCT02187861 | Completed Phase 2 Results

• 2 other identifiers: BO293372014-000576-26
• Study Type: interventional
• Target: 163
• Locations: 8 countries
• Sites: 71

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

Outcome Measures

Primary Outcomes (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)

  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.

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

Secondary Outcomes (23)

• 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)

• 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)

• 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)

• 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)

• 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)

Study Arms (4)

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

EXPERIMENTAL

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; Drug: Bendamustine; Drug: Rituximab

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

EXPERIMENTAL

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; Drug: Rituximab

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

EXPERIMENTAL

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; Drug: Bendamustine; Drug: Rituximab

Chemotherapy-Containing Cohort: Arm C (BR)

ACTIVE COMPARATOR

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; Drug: Rituximab

Interventions

Venetoclax DRUG

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

Also known as: GDC-0199, ABT-199

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR); Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR); Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)

Bendamustine DRUG

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

Also known as: Levact

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR); Chemotherapy-Containing Cohort: Arm C (BR); Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR)

Rituximab DRUG

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

Also known as: MabThera, Rituxan

Chemotherapy-Containing Cohort: Arm B (Venetoclax + BR); Chemotherapy-Containing Cohort: Arm C (BR); Chemotherapy-Containing Cohort:Safety Run-In (Venetoclax + BR); Chemotherapy-Free Cohort: Arm A (Venetoclax + Rituximab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• AbbVie: collaborator

Study Sites (71)

Southern Cancer Center, PC

Mobile, Alabama, 36608, United States

Location

Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

UCLA School of Medicine; Hematology/Oncology

Los Angeles, California, 90095, United States

Location

Nothwest Georgia Oncology Centers P.C

Austell, Georgia, 30106, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Illinois at Chicago College of Medicine

Chicago, Illinois, 60612-7302, United States

Location

Primary Healthcare Associates SC - Harvey

Harvey, Illinois, 60426, United States

Location

University of Kansas; Medical Center & Medical pavilion

Westwood, Kansas, 66205, United States

Location

Sidney Kimmel Comp Cancer Ctr

Baltimore, Maryland, 21231-1000, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

James P. Wilmot Cancer Center

Rochester, New York, 14642, United States

Location

University of Pennsylvania; School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

VCU Massey Cancer Center

Richmond, Virginia, 23298-003, United States

Location

West Virginia Uni Med. Center - Robert Byrd Health Science

Morgantown, West Virginia, 26506, United States

Location

Royal Prince Alfred Hospital; Medical Oncology

Camperdown, New South Wales, 2050, Australia

Location

St George Hospital

Kogarah, New South Wales, New South Wales, 2217, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Westmead Hospital; Haematology

Sydney, New South Wales, 2145, Australia

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

Location

Townsville General Hospital

Douglas, Queensland, 4184, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Queen Elizabeth Hospital; Haematology

Woodville South, South Australia, 5011, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

ZNA Stuivenberg

Antwerp, 2060, Belgium

Location

AZ Sint Jan

Bruges, 8000, Belgium

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

British Columbia Cancer Agency

Kelowna, British Columbia, V1Y 5L3, Canada

Location

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, M5G 2M9, Canada

Location

Hopital Maisonneuve- Rosemont; Oncology

Montreal, Quebec, H1T 2M4, Canada

Location

Chum Hopital Notre Dame; Centre D'Oncologie

Montreal, Quebec, H2L 4M1, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Saskatoon Cancer Centre; Uni of Saskatoon Campus

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Institut de Cancerologie de l'Ouest

Angers, 49933, France

Location

CHU Clermont Ferrand - Hôpital d'Estaing

Clermont-Ferrand, 63003, France

Location

Hopital Henri Mondor

Créteil, 94010, France

Location

CHU de Dijon - Hopital le Bocage

Dijon, 21000, France

Location

Centre Jean Bernard

Le Mans, 72015, France

Location

CHU Montpellier

Montpellier, 34295, France

Location

Centre Hospitalier Lyon Sud; Hematolgie

Pierre-Bénite, 69495, France

Location

Klinikum Chemnitz gGmbH; Klinik f. Innere Medizin III

Chemnitz, 09116, Germany

Location

Universitätsklinikum Köln; Klinik I für Innere Medizin

Cologne, 50937, Germany

Location

Städtisches Klinikum Dessau

Dessau, 06847, Germany

Location

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

Dresden, 01307, Germany

Location

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

Essen, 45122, Germany

Location

Universitätsklinikum Jena; Klinik für Innere Medizin II

Jena, 07747, Germany

Location

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

Lübeck, 23562, Germany

Location

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

Mainz, 55131, Germany

Location

Universitätsklinikum Ulm; Apotheke

Ulm, 89075, Germany

Location

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

Würzburg, 97080, Germany

Location

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

Bologna, Emilia-Romagna, 40138, Italy

Location

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

Meldola, Emilia-Romagna, 47014, Italy

Location

Ospedale di Ravenna

Ravenna, Emilia-Romagna, 48100, Italy

Location

Ospedale Infermi di Rimini

Rimini, Emilia-Romagna, 47900, Italy

Location

Asst Papa Giovanni XXIII

Bergamo, Lombardy, 24100, Italy

Location

Ospedale Niguarda Milano

Milan, Lombardy, 20162, Italy

Location

Irccs Policlinico San Matteo; Divisione Di Ematologia

Pavia, Lombardy, 27100, Italy

Location

Azienda Ospedale San Giovanni

Turin, Piedmont, 10126, Italy

Location

Az. Osp. Di Careggi; Divisione Di Ematologia

Florence, Tuscany, 50135, Italy

Location

Blackpool Victoria Hospital

Blackpool, FY3 8NR, United Kingdom

Location

St James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Leicester Royal Infirmary; Dept. of Medical Oncology

Leicester, LE1 5WW, United Kingdom

Location

University College London, Department of Haematology

London, NW1 2PG, United Kingdom

Location

Royal Marsden Nhs Trust; Consultant Cancer Physician

London, SW3 6JJ, United Kingdom

Location

Christie Hospital; Breast Cancer Research Office

Manchester, M20 4QL, United Kingdom

Location

Churchill Hospital; Oxford Cancer and Haematology Centre

Oxford, OX3 7LJ, United Kingdom

Location

Royal Marsden NHS Foundation Trust

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 32785666 DERIVED

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

venetoclax; Bendamustine Hydrochloride; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2014
• First Posted: July 11, 2014
• Study Start: December 1, 2014
• Primary Completion: September 27, 2016
• Study Completion: March 16, 2018
• Last Updated: June 5, 2019
• Results First Posted: October 13, 2017

Record last verified: 2019-06

Locations

FR (7); IT (9); GB (8); US (17); AU (10); BE (3); DE (10); CA (7)