MRD Guided Sonrotoclax and Zanubrutinib in Newly Diagnosed CLL/SLL

Trial Title: MRD Guided Sonrotoclax and Zanubrutinib in Newly Diagnosed CLL/SLL

NCT ID: NCT06367374

Condition: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma

Conditions: Official terms:
Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Zanubrutinib

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Sonrotoclax
Description: 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.
Arm group label: Sonrotoclax Plus Zanubrutinib

Other name: BGB-11417

Intervention type: Drug
Intervention name: Zanubrutinib
Description: 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.
Arm group label: Sonrotoclax Plus Zanubrutinib

Other name: BGB- 3111

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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Treatment naïve adult patients with diagnosis of CLL/SLL requiring treatment according to iwCLL guidelines 2018 2. Measurable nodal disease by CT/MRI. 3. Adequate hematologic function 4. Adequate hepatic and renal function 5. Eastern Cooperative Oncology Group 6. (ECOG) performance status of 0-2 7. Expected survival period > 6 months Exclusion Criteria: 1. Any prior systemic therapy used for treatment of CLL/SLL 2. With history of prolymphocytic leukemia, known or currently suspected Richter's transformation 3. Known central nervous system involvement by leukemia or lymphoma 4. Confirmed progressive multifocal leukoencephalopathy (PML) 5. Severe or debilitating pulmonary disease 6. Clinically significant cardiovascular disease 7. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura requiring treatment 8. History of other malignancies 9. Prior therapy with study drugs within 4 weeks before screening 10. Active fungal, bacterial, and/or viral infection requiring systemic therapy 11. Known allergy to zanubrutinib or sonrotoclax or any pharmaceutical excipients 12. Pregnant or lactating women 13. Vaccinated with live vaccines within 28 days prior to enrollment 14. Serologically positive of human immunodeficiency virus (HIVAb), or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) 15. History of stroke or intracranial hemorrhage within 6 months 16. Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Start date: May 30, 2024

Completion date: July 30, 2030

Lead sponsor:
Agency: Institute of Hematology & Blood Diseases Hospital, China
Agency class: Other

Source: Institute of Hematology & Blood Diseases Hospital, China

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06367374