Sonrotoclax, Rituximab, and Zanubrutinib in Treating Participants With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma

This phase II trial studies the side effects of an escalated ramp-up of sonrotoclax following initial debulking with zanubrutinib or rituximab in treating patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL) that is newly diagnosed, has come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Rituximab is a monoclonal antibody that binds to a protein called CD20, which is found on B-cells, and may kill tumor cells. Zanubrutinib may stop the growth of tumor cells by blocking a protein called Bruton's tyrosine kinase (BTK), which is needed for tumor cell growth. Sonrotoclax works by blocking a protein called B-cell lymphoma-2 (BCL-2). This protein helps certain types of blood tumor cells to survive and grow. When sonrotoclax blocks Bcl-2 it slows down or stops the growth of tumor cells and helps them die. Giving an increased dose of sonrotoclax over a shorter period of time in combination with zanubrutinib or rituximab may be safe and tolerable in treating patients with newly diagnosed, relapsed or refractory CLL, SLL, and MCL.

NCT Number	NCT06839053
Lead Sponsor	Fred Hutchinson Cancer Center Collaborators: BeOne Medicines
Conditions	Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma, Recurrent Chronic Lymphocytic Leukemia, Recurrent Mantle Cell Lymphoma, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Refractory Mantle Cell Lymphoma, Refractory Small Lymphocytic Lymphoma +1 more
Enrollment	30 participants
Start Date	2025-06-02
Primary Completion	2028-08-01 (estimated)
Study Completion	2032-07-01 (estimated)
Updated on ClinicalTrials.gov	2026-04-22