MRD Guided Sonrotoclax and Zanubrutinib in Newly Diagnosed CLL/SLL

Chronic Lymphocytic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06367374
• Other study ID #: BGB-11417-2002-IIT;BDH-CLL-004
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 30, 2024
• Est. completion date: July 30, 2030

Study information

• Verified date: April 2024
• Source: Institute of Hematology & Blood Diseases Hospital, China
• Contact: Shuhua Yi
• Phone: 15900265415
• Email: yishuhua[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 66
• Est. completion date: July 30, 2030
• Est. primary completion date: February 28, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Small Lymphocytic Lymphoma

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital, China

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Rate of peripheral blood (PB) and Bone marrow (BM) undetectable minimal residual disease (uMRD)	Rate of PB and BM uMRD is defined as proportion of participants achieving remission based on flow cytometry (FCM) result of < 1 CLL cell per 100,000 leukocytes (< 10 ^-4 ), after completion of 12 and 24 cycles of sonrotoclax treatment.	At screening, the end of Cycle 14 and Cycle 26 (each cycle is 28 days)
Secondary	Complete Response Rate (CRR; Complete Response/Complete Response with Incomplete Blood Count Recovery [CR/CRi]) Rate	CR/CRi rate is defined as the percentage of participants achieving a response of complete response (CR), CR with incomplete blood count recovery (CRi) per 2018 IWCLL criteria, as determined by investigators	Up to 4 years
Secondary	Overall Response Rate (ORR)	ORR is defined as the percentage of participants achieving a response of complete response (CR), CR with incomplete blood count recovery (CRi), nodular partial response (nPR), partial response (PR), or PR with lymphocytosis (PRL) evaluated under the 2018 IWCLL criteria, as determined byinvestigators	Up to 4 years
Secondary	Duration of Response (DOR)	DOR was calculated for participants achieving a response (CR, CRi, nPR, PR) based on 2018 IWCLL response criteria in CLL or a response (PR or better) based on 2014 Lugano response criteria and defined as the interval between the date of initial documentation of a response mentioned above until disease progression (PD) or death from any cause, whichever occurred first	Up to 4 years
Secondary	Progression Free Survival (PFS)	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	Up to 4 years
Secondary	Overall Survival (OS)	OS is defined as time from the date of enrollment to the date of death because of any cause	Up to 4 years
Secondary	Time to Next Therapy (TTNT)	Time to next CLL or SLL therapy is defined as the time from the first administration of study drugs to the first administration of the next CLL/SLL treatment, as determined by investigators	Up to 4 years
Secondary	Overall survival rate	Number, time frame and seriousness of participants with Treatment-Emergent Adverse Events (NCI-TEAE v5.0)	Up to 4 years