Evaluating Zanubrutinib Combined with Sonrotoclax for Newly Diagnosed High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma in Adults Aged 18 to 75

What this Trial Is About

Researchers are evaluating a new treatment approach for patients with previously untreated high-risk chronic lymphocytic leukemia CLL or small lymphocytic lymphoma SLL. This phase II clinical trial studies the efficacy and safety of a combination therapy guided by minimal residual disease MRD status, using zanubrutinib plus sonrotoclax. The goal is to assess time-limited therapy effectiveness in this patient population. Participants receive oral zanubrutinib at 160 mg twice daily until Cycle 15, 21, or 27, or until disease progression or unacceptable toxicity occurs. Sonrotoclax treatment begins in Cycle 3 with a 4-week dose escalation to reach 320 mg daily, followed by continued therapy until the same cycle limits or discontinuation criteria are met. Patients must complete at least 12 cycles of combination therapy, with a maximum of 24 cycles. If MRD negativity uMRD6 is not achieved after 24 cycles, zanubrutinib monotherapy is continued as maintenance. Treatment may be stopped earlier if uMRD6 is achieved. During the study, participants undergo regular assessments, including evaluation of MRD status at several time points up to Cycle 25, and response rates at specified cycles. Safety is monitored daily during treatment. The primary outcome is the rate of MRD negativity at Cycle 15. Secondary outcomes include response rates, progression-free survival, overall survival, and adverse events over a follow-up period of up to three years. The total participation duration extends until study completion or disease progression.

A Study of MRD-Guided Zanubrutinib Plus Sonrotoclax in Treatment-Naïve, High-Risk CLL/SLL Patients