MRD Guided Sonrotoclax and Zanubrutinib in Newly Diagnosed CLL/SLL

NCT ID: NCT06367374

Last Updated: 2024-04-16

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-30
• Study Completion Date: 2030-07-30

Brief 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sonrotoclax Plus Zanubrutinib

• Participants will receive from the start of Cycle 1 a standard dose of zanubrutinib twice daily orally for three cycles and in combination with sonrotoclax starting from Cycle 4 onwards at increasing doses twice a week until the target dose is reached from Cycle 5 and continuing until the end of Cycle 15 (each cycle is 28 days). Patients with a measurable minimal residual disease (MRD) will receive another 12 cycles of Zanubrutinib in combination with sonrotoclax until their MRD is undetectable.
• Interventions:

• Drug: Sonrotoclax
• Drug: Zanubrutinib

Group Type: EXPERIMENTAL

Sonrotoclax

Intervention Type: DRUG

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.

Zanubrutinib

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

BGB-11417; BGB- 3111

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Qiu Lugui

Institute of Hematology & Blood Diseases Hospital, China

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lugui Qiu

Role: PRINCIPAL_INVESTIGATOR

Institute of Hematology & Blood Diseases Hospital, China

Central Contacts

Shuhua Yi

Role: CONTACT

yishuhua@ihcams.ac.cn

15900265415

Yexiang Wang

Role: CONTACT

yexiang.wang@ashermed.com

13810279737

Other Identifiers

BGB-11417-2002-IIT；BDH-CLL-004

Identifier Type: -

Identifier Source: org_study_id