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NCT Number: NCT06367374

MRD Guided Sonrotoclax and Zanubrutinib in Newly Diagnosed CLL/SLL

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.

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Key information

Conditions

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

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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
  • Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor

Treatment and study plan

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.

Other names: BGB-11417

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.

Other names: BGB- 3111

Primary outcomes

  1. 4-Year Progressive Free Survival (PFS) Rate

    Time frame: 4 years after enrollment

    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

Secondary outcomes

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

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

    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.

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

    Time frame: Up to 4 years

    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

  3. Overall Response Rate (ORR)

    Time frame: Up to 4 years

    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

  4. Duration of Response (DOR)

    Time frame: Up to 4 years

    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

  5. Progression Free Survival (PFS)

    Time frame: Up to 4 years

    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

  6. Overall Survival (OS)

    Time frame: Up to 4 years

    OS is defined as time from the date of enrollment to the date of death because of any cause

  7. Time to Next Therapy (TTNT)

    Time frame: Up to 4 years

    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

  8. Overall survival rate

    Time frame: Up to 4 years

    Number, time frame and seriousness of participants with Treatment-Emergent Adverse Events (NCI-TEAE v5.0)

Study contacts

Contact information is provided by the study sponsor or research team.

Shuhua Yi

CONTACT

[email protected]

15900265415

Yexiang Wang

CONTACT

[email protected]

13810279737

Sponsors and collaborators

Lead sponsor

Institute of Hematology & Blood Diseases Hospital, China

Other

Registry information

Official study 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

Important dates

Study start
2024
Primary completion
2030
Study completion
2030
First posted
Apr 16, 2024
Registry last updated
Apr 16, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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