Zanubrutinib and Venetoclax as Initial Therapy for Chronic Lymphocytic Leukemia (CLL) With Response-based Obinutuzumab
Leukemia, Lymphocytic, Chronic, B-Cell
About this trial
This is an interventional treatment trial for Leukemia, Lymphocytic, Chronic, B-Cell focused on measuring Chronic Lymphocytic Leukemia, CLL, Small Lymphocytic Lymphoma, SLL
Eligibility Criteria
Inclusion Criteria: Participant must have confirmed diagnosis of CLL/SLL Participant must have indications for treatment Participants of childbearing potential must be willing to comply with pregnancy prevention interventions Exclusion Criteria: Previous exposure to any systemic anti-cancer therapy as a treatment for CLL/SLL, including but not limited to chemotherapy, immunotherapy, radiotherapy, hormone therapy (other than contraceptives, hormone-replacement therapy or megestrol acetate) or investigational therapy. History of malignancy except for non-melanoma skin cancers. Participants treated with curative intent via methods of local resection and or locally targeted anticancer treatment and are free of malignancy for at least 5 years from treatment end will be allowed to enroll. Requires chronic immunosuppressive therapy for any reason or was treated with immunosuppressive therapy within 6 months of study entry. Participants with active autoimmune hemolytic anemia or immune thrombocytopenia purpura. Prolymphocytic leukemia or Richter's Transformation. Active bleeding, or history of bleeding diathesis (e.g., hemophilia or von Willebrand disease). Participant requires warfarin or equivalent vitamin K antagonist. Uncontrolled or active significant infection requiring systemic treatment History of suspected or confirmed PML Myocardial infarction within 6 months before screening. Unstable angina within 3 months before screening. New York Heart Association class III or IV congestive heart failure History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes). Patients with stroke or CNS hemorrhage within 6 months. Pregnant or breastfeeding. Major surgical procedure within 28 days of first dose of study drug. Has difficulty with or is unable to swallow oral medication or has significant gastrointestinal disease that would limit absorption of oral medication. Participant is positive for human immunodeficiency virus (HIV). Known hypersensitivity reactions (e.g., anaphylaxis) to obinutuzumab or any of the excipients, including serum sickness with prior obinutuzumab use. Vaccination with live vaccine ≤28 days prior to start of treatment.
Sites / Locations
- Weill Cornell Medicine/NewYork-Presberteryian HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Double Therapy (Zanubrutinib plus Venetoclax)
Triple Therapy (Zanubrutinib, Venetoclax, and Obinutuzumab)
All participants will receive an initial 3 cycles of zanubrutinib monotherapy. This lead-in period will then be followed by 12 cycles of zanubrutinib and venetoclax combination therapy. All participants will complete 12 cycles of zanubrutinib and venetoclax combination therapy or 15 cycles of total treatment. Peripheral blood and bone marrow MRD assessments will occur at C16D1. Participants will continue on double combination treatment for an additional 1 month while results of MRD testing are obtained. In total, all participants will be on treatment for at least 16 full cycles. Participants that meet definition of MRD negativity will stop therapy at C17D1 and enter an observation phase with study visits every 3 months. Participants that remain MRD positive at C16D1 will enter the triple therapy (zanubrutinib, venetoclax, and obinutuzumab) arm.
Participants that meet definition of MRD positivity at C16D1 will enter the triple therapy arm (zanubrutinib, venetoclax, and obinutuzumab). These participants will continue combination therapy with zanubrutinib and venetoclax, but will also receive 6 cycles of obinutuzumab starting at C17D1. In this subgroup, peripheral blood and bone marrow MRD assessments will occur after an additional 6 cycles of the triplet combination therapy (C23D1) at which point all participants will stop study treatment regardless of MRD status.