A Study Comparing BGB-3111 With Bendamustine Plus Rituximab in Patients With Previously Untreated CLL or SLL

Status: Active

Description

This study will enroll subjects with previously untreated CLL / SLL into three cohorts (Cohort 1 without del[17p] and Cohorts 2 and 3 with del[17p]). Cohort 1 subjects will receive either zanubrutinib alone or "bendamustine (B) and rituximab (R)". Cohort 2 subjects will receive zanubrutinib alone. Once Cohort 2 has finished enrollment, Cohort 3 will be opened in selected countries / sites where patients will receive zanubrutinib and venetoclax. The primary purpose is to evaluate the efficacy and safety of zanubrutinib versus bendamustine and rituximab in Cohort 1.

Eligibility Criteria

Inclusion Criteria

  • Inclusion Criteria: All subjects - Unsuitable for chemoimmunotherapy with FCR - Confirmed diagnosis of CD20-positive CLL or SLL, requiring treatment. - Measurable disease by imaging - ECOG performance status of 0, 1 or 2. - Life expectancy ≥ 6 months. - Adequate bone marrow function. - Adequate renal and hepatic function. Exclusion Criteria: All subjects - Previous systemic treatment for CLL/SLL. - Requires ongoing need for corticosteroid treatment. - Known prolymphocytic leukemia or history of or suspected Richter's transformation. - Clinically significant cardiovascular disease. - Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix of breast, or localized Gleason score 6 prostate cancer. - History of severe bleeding disorder. - History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug. - Severe or debilitating pulmonary disease. - Inability to swallow capsules or disease affecting gastrointestinal function. - Active infection requiring systemic treatment. - Known central nervous system involvement by leukemia or lymphoma - Underlying medical condition that will render the administration of study drug hazardous or obscure interpretation of toxicity or AEs - Known infection with human immunodeficiency virus (HIV) or active hepatitis B or C infection. - Major surgery ≤ 4 weeks prior to start of study treatment. - Pregnant or nursing females. - Vaccination with live vaccine within 35 days prior to the first dose of study drug. - Ongoing alcohol or drug addiction - Known hypersensitivity to zanubrutinib, bendamustine, rituximab, or venetoclax (as applicable) or any other ingredients of the study drugs. - Requires ongoing treatment with strong CYP3A inhibitor or inducer. - Concurrent participation in another therapeutic clinical trial.

Locations & Contacts

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Name Not Available
Dana-Farber Cancer Institute
Status: Active
Name Not Available

New York

New York
Memorial Sloan Kettering Cancer Center
Status: Active
Name Not Available

North Carolina

Durham
Duke University Medical Center
Status: Active
Name Not Available

Oregon

Portland
OHSU Knight Cancer Institute
Status: Active
Name Not Available

Virginia

Charlottesville
University of Virginia Cancer Center
Status: Active
Name Not Available

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: Active
Name Not Available

Trial Objectives and Outline

This is a global phase 3, open label, randomized study of zanubrutinib versus bendamustine plus rituximab (B+R) in subjects with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL), including subjects without del(17p) [Cohort 1] and subjects with del(17p) [Cohort 2 and Cohort 3]. Subjects in Cohort 1 are randomized 1:1 to zanubrutinib (Arm A) or bendamustine plus rituximab (Arm B). Randomization will be stratified by age, Binet stage, immunoglobulin variable region heavy chain (IGHV) mutational status, and geographic region. Subjects in Cohort 2 will receive treatment with zanubrutinib. Subjects in Cohort 3 will receive treatment with zanubrutinib and venetoclax.

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
BeiGene

Trial IDs

Primary ID BGB-3111-304
Secondary IDs NCI-2017-02160, 2017-001551-31, CTR20190416, BGB-3111-304 (Sequoia)
Clinicaltrials.gov ID NCT03336333