NCT06367374

MRD Guided Sonrotoclax and Zanubrutinib in Newly Diagnosed CLL/SLL

A Single Arm, Open-label Study of MRD-Guided Zanubrutinib in Combination With Sonrotoclax in Adult Patients With Treatment Naïve Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 66 (estimated)
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a single-arm, open-label study of sonrotoclax plus zanubrutinib with MRD-driven treatment duration in patients with previously untreated Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). The primary goal of this study is to evaluate the efficacy of MRD-guided zanubrutinib plus sonrotoclax for first-line CLL/SLL treatment.

Detailed description

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are often considered different variations of the same disease due to their many similarities. There is an urgent need for new treatments to improve patients' quality of life, prolong survival, and manage disease-related symptoms. There are several different methods for treating front-line therapy, including Chemoimmunotherapy (CIT), Bruton tyrosine kinase inhibitors (BTKis), and BCL-2 inhibitors (BCL2is). Continuous treatment with BTK inhibitors is necessary for the treatment of CLL or SLL. However, younger patients may need to limit their therapeutic duration. The combination of BTK inhibitors and BCL-2 inhibitors is believed to be an optimizing regimen that provides a limited duration of therapy. The main aim of this study is to assess whether MRD-guided zanubrutinib, in combination with sonrotoclax, can be an effective first-line treatment option for adult patients with treatment-naïve CLL or SLL. The goal is to achieve long-lasting and more profound responses, which could allow for the possibility of discontinuing treatment.

Conditions

• Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma

Interventions

Type	Name	Description
DRUG	Sonrotoclax	Participants receive zanubrutinib orally 160mg bid from start of Cycle 1, and in combination with sonrotoclax (SZ) from Cycle 4 onwards at increasing doses until 320mg daily target dose is reached and continuing for at least 12 cycles (each cycle is 28 days). Participants with uMRD and PR/CR by the end of Cycle 15 will stop SZ treatment, others will continue to receive SZ for another 12 cycles and stop SZ if uMRD and PR/CR. Participants will receive sonrotoclax up to 2 years, and receive zanubrutinib for those with MRD-positive by then.
DRUG	Zanubrutinib	Participants receive zanubrutinib orally 160mg bid from start of Cycle 1,Participants with uMRD and PR/CR by the end of Cycle 15 will stop SZ treatment, others will continue to receive SZ for another 12 cycles and stop SZ if uMRD and PR/CR. Participants will receive sonrotoclax up to 2 years, and receive zanubrutinib for those with MRD-positive by then.

Timeline

• Start date: 2024-05-30
• Primary completion: 2030-02-28
• Completion: 2030-07-30
• First posted: 2024-04-16
• Last updated: 2024-04-16