Clinical trial NCT06367374: MRD Guided Sonrotoclax and Zanubrutinib in Newly Diagnosed CLL/SLL
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2024-04-16
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 4-Year Progressive Free Survival (PFS) Rate
timeFrame: 4 years after enrollment
Secondary outcomes:
measure: Rate of peripheral blood (PB) and Bone marrow (BM) undetectable minimal residual disease (uMRD)
timeFrame: At screening, the end of Cycle 14 and Cycle 26 (each cycle is 28 days)
measure: Complete Response Rate (CRR; Complete Response/Complete Response with Incomplete Blood Count Recovery [CR/CRi]) Rate
timeFrame: Up to 4 years
measure: Overall Response Rate (ORR)
timeFrame: Up to 4 years
measure: Duration of Response (DOR)
timeFrame: Up to 4 years
measure: Progression Free Survival (PFS)
timeFrame: Up to 4 years
measure: Overall Survival (OS)
timeFrame: Up to 4 years
measure: Time to Next Therapy (TTNT)
timeFrame: Up to 4 years
measure: Overall survival rate
timeFrame: Up to 4 years
Other outcomes:
Locations:
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Lugui Qiu
role: PRINCIPAL_INVESTIGATOR
References: