Study of Sonrotoclax With Zanubrutinib or Rituximab in Treating Adults With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Mantle Cell Lymphoma

What this Trial Is About

Researchers are evaluating an escalated ramp-up dosing schedule of sonrotoclax combined with either zanubrutinib or rituximab in patients with chronic lymphocytic leukemia CLL, small lymphocytic lymphoma SLL, or mantle cell lymphoma MCL. These patients may have newly diagnosed disease, relapsed after previous treatment, or refractory disease that does not respond to prior therapy. The study aims to assess the side effects and tolerability of this combination treatment approach in these blood cancers. Participants are assigned to one of two treatment groups based on whether they are refractory to Brutons tyrosine kinase inhibitors BTKi. In the first group, patients not refractory to BTKi receive oral zanubrutinib daily for 15 cycles, each lasting 28 days. Starting cycle 4, sonrotoclax is introduced and gradually increased to the target dose, continuing with zanubrutinib through cycle 15. In the second group, patients refractory to BTKi receive rituximab intravenously over one cycle and then begin sonrotoclax ramp-up from cycle 2, continuing sonrotoclax through cycle 13 alongside rituximab infusions during cycles 3 to 6. Both groups undergo computed tomography scans during screening and treatment, blood sample collections, and may have bone marrow biopsies and endoscopies. After finishing the treatment cycles, participants are followed closely at 14 days, 1 month, and then monitored up to five years. Researchers collect safety data including adverse events and track the ability to reach specific sonrotoclax dose levels early in the ramp-up. They also assess long-term outcomes such as overall response rates, progression-free survival, and overall survival. The study includes detailed imaging, laboratory tests, and clinical evaluations throughout and after treatment to understand the treatments effects and safety profile.

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