MRD Guided Sonrotoclax and Zanubrutinib in Newly Diagnosed CLL/SLL

NCT06367374 | Not Yet Recruiting Phase 2

• 1 other identifier: BGB-11417-2002-IIT；BDH-CLL-004
• Study Type: interventional
• Target: 66
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (1)

• 4-Year Progressive Free Survival (PFS) Rate

  PFS is defined as the time from the date of enrollment to the date of first confirmed disease progression or death due to any cause, whichever occurs first, as determined by investigators

  4 years after enrollment

Secondary Outcomes (8)

• Rate of peripheral blood (PB) and Bone marrow (BM) undetectable minimal residual disease (uMRD)

  At screening, the end of Cycle 14 and Cycle 26 (each cycle is 28 days)

• Complete Response Rate (CRR; Complete Response/Complete Response with Incomplete Blood Count Recovery [CR/CRi]) Rate

  Up to 4 years

• Overall Response Rate (ORR)

  Up to 4 years

• Duration of Response (DOR)

  Up to 4 years

• Progression Free Survival (PFS)

  Up to 4 years

Study Arms (1)

Sonrotoclax Plus Zanubrutinib

EXPERIMENTAL

* 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

Drug: Sonrotoclax; Drug: Zanubrutinib

Interventions

Sonrotoclax 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.

Also known as: BGB-11417

Sonrotoclax Plus Zanubrutinib

Zanubrutinib 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.

Also known as: BGB- 3111

Sonrotoclax Plus Zanubrutinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Treatment naïve adult patients with diagnosis of CLL/SLL requiring treatment according to iwCLL guidelines 2018
• Measurable nodal disease by CT/MRI.
• Adequate hematologic function
• Adequate hepatic and renal function
• Eastern Cooperative Oncology Group
• (ECOG) performance status of 0-2
• Expected survival period \> 6 months

You may not qualify if:

• Any prior systemic therapy used for treatment of CLL/SLL
• With history of prolymphocytic leukemia, known or currently suspected Richter's transformation
• Known central nervous system involvement by leukemia or lymphoma
• Confirmed progressive multifocal leukoencephalopathy (PML)
• Severe or debilitating pulmonary disease
• Clinically significant cardiovascular disease
• Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura requiring treatment
• History of other malignancies
• Prior therapy with study drugs within 4 weeks before screening
• Active fungal, bacterial, and/or viral infection requiring systemic therapy
• Known allergy to zanubrutinib or sonrotoclax or any pharmaceutical excipients
• Pregnant or lactating women
• Vaccinated with live vaccines within 28 days prior to enrollment
• Serologically positive of human immunodeficiency virus (HIVAb), or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
• History of stroke or intracranial hemorrhage within 6 months

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

zanubrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lugui Qiu

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shuhua Yi

CONTACT

15900265415; yishuhua@ihcams.ac.cn

Yexiang Wang

CONTACT

13810279737; yexiang.wang@ashermed.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Institute of Hematology & Blood Diseases Hospital, China

Study Record Dates

• First Submitted: March 20, 2024
• First Posted: April 16, 2024
• Study Start: May 30, 2024
• Primary Completion (Estimated): February 28, 2030
• Study Completion (Estimated): July 30, 2030
• Last Updated: April 16, 2024

Record last verified: 2024-04