MRD Guided Sonrotoclax and Zanubrutinib in Newly Diagnosed CLL/SLL

Institute of Hematology & Blood Diseases Hospital, China

Status and phase: Not yet enrolling; Phase 2

Conditions: Small Lymphocytic Lymphoma; Chronic Lymphocytic Leukemia

Treatments: Drug: Zanubrutinib; Drug: Sonrotoclax

Study type: Interventional

Funder types: Other

Identifiers

NCT06367374

BGB-11417-2002-IIT；BDH-CLL-004

Details and patient eligibility

About

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.

Full 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.

Enrollment: 66 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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66 participants in 1 patient group

Sonrotoclax Plus Zanubrutinib

Experimental group

Description:

* 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

Treatment:

Drug: Sonrotoclax

Drug: Zanubrutinib