What this Trial Is About

The trial investigates treatment options for patients with Richter Transformation (RT), a challenging progression of chronic lymphocytic leukemia (CLL) with poor prognosis and limited effective therapies. RT patients often respond poorly to conventional chemoimmunotherapy, and many are not suitable candidates for allogeneic transplantation. This phase II trial aims to assess the safety and effectiveness of combining zanubrutinib, a BTK inhibitor, with tislelizumab, a PD-1 inhibitor, with or without sonrotoclax, a Bcl-2 inhibitor, to improve outcomes in this patient group. Participants receive treatment in cycles every 21 days. Zanubrutinib is taken orally twice daily at 160 mg. Tislelizumab is administered intravenously at 200 mg on day 1 of each cycle. For those receiving sonrotoclax, there is an initial ramp-up phase during cycle 1 with increasing doses from 2 mg to 320 mg daily, followed by a maintenance dose of 320 mg daily from cycle 2 to cycle 6. The study evaluates the combination of these drugs systematically to monitor safety and treatment response. During the study, participants undergo regular assessments including evaluations of overall response rate after 18 weeks based on refined Lugano Classification criteria. Researchers monitor safety, toxicity, and efficacy through clinical visits, laboratory tests, and imaging as needed. Patients must meet specific health criteria and provide informed consent to participate. The trial includes ongoing monitoring for adverse effects and treatment adherence over the course of therapy to better understand the potential of these drug combinations for RT.

Efficacy and Safety of Zanubrutinib Plus Tislelizumab Treatment with or Without Sonrotoclax for Patients with Richter Transformation