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Study of Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Obinutuzumab in Participants With Chronic Lymphocytic Leukemia (CLL)

Primary Purpose

CLL

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Sonrotoclax
Zanubrutinib
Venetoclax
Obinutuzumab
Sponsored by
BeiGene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for CLL focused on measuring CLL, Chronic Lymphocytic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Treatment-naïve (TN) adults with confirmed diagnosis of CLL which requires treatment Eastern Cooperative Oncology Group (ECOG) score 0, 1, or 2 Measurable disease by Computer Tomography/Magnetic Resonance Imaging Adequate liver function as indicated by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x the institutional upper limits of normal (ULNs) value; serum total bilirubin < 3.0 x ULN Adequate renal function as defined as creatinine clearance ≥ 50 milliliters per minute Exclusion Criteria: Previous systemic treatment for CLL Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation Known central nervous system involvement History of confirmed progressive multifocal leukoencephalopathy (PML) Uncontrolled hypertension Note: Other protocol defined criteria may apply

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Sonrotoclax Plus Zanubrutinib

    Venetoclax Plus Obinutuzumab

    Arm Description

    Participants will receive from start of Cycle 1 a standard dose of zanubrutinib once or twice daily orally and in combination with sonrotoclax starting from Cycle 4 onwards at increasing doses until target dose is reached and continuing until end of Cycle 15 (each cycle is 28 days)

    Participants will receive obinutuzumab 100mg intravenously on Day 1 Cycle 1, followed by 900 mg on Day 2 Cycle 1 (or alternatively receive 1000 mg intravenously on Day 1), followed by 1000 mg on Days 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2 through 6 (each cycle is 28 days) in combination with venetoclax at increasing doses until target dose is reached from Day 22 Cycle 1 until end of Cycle 12 (each cycles is 28 days)

    Outcomes

    Primary Outcome Measures

    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 independent review committee (IRC)

    Secondary Outcome Measures

    Complete Response Rate (CRR)
    CRR is defined as the percentage of participants that achieved best response of complete response (CR)/ complete response with incomplete hematopoietic recovery (CRi), determined by IRC.
    Rates of Undetectable Measurable Residual Disease
    Undetectable measurable residual disease uMRD4 rate at the first Post- Treatment Follow-up (PTFU 1) Visit will be based on next-generation sequencing.
    Overall Survival (OS)
    OS is defined as time from the date of enrollment to the date of death because of any cause
    PFS by Investigator Assessment
    FS 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 investigator assessment
    CRR by Investigator Assessment
    CRR is defined as the percentage of participants that achieved best response of complete response (CR)/ complete response with incomplete hematopoietic recovery (CRi), determined by Investigator Assessment
    Rates of uMRD4 Based on Flow-Cytometry
    The overall uMRD4 rate is defined as the proportion of participants who achieve uMRD status in peripheral blood before disease progression or start of new anti-CLL treatment (whichever is earlier), based on flow cytometry.
    Overall Response Rate (ORR) Determined by IRC and Investigator Assessment
    ORR is defined as the percentage of participants who achieve a response (CR, CRi, nodular partial remission (nPR), partial response (PR), and partial response with lymphocytosis [PR-L]), before disease progression or start of new anti-CLL treatment (whichever is earlier).
    Duration of Response (DOR) by IRC and Investigator Assessment
    Duration of response (DOR) is defined as the time from first qualifying response PR, PR-L, CR, or CRi) until CLL progression or death.
    Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
    The Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
    Global health status (GHS)/qualify of life (QoL) and physical functioning measured by EORTC QLQ-C30 The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 =Not at all (best) to 4 =Very Much (worst) and 2 questions answered on a 7-point scale where 1 =Very poor (worst) to 7 =Excellent (best).
    HRQoL) as Assessed by EORTC QLQ-C30 CLL Module Quality of Life Questionnaire - Chronic Lymphocytic Leukemia Module 17 Items (QLQ-CLL17)
    The symptom burden and physical condition/fatigue will be measured by QLQ-CLL17. EORTC QLQ-CLL17 comprises 17 items grouped into 3 multi-item scales: 1) symptom burden, 2) physical condition/fatigue, and 3) worries/fears about health and functioning. The EORTC QLQ-CLL17 will be scored according to the EORTC QLQ-C30 Scoring Manual. An outcome variable consisting of a score from 0 to 100 will be derived for each of the symptom scales, each of the functional scales, and the global measure of health status scale. Higher scores on the global measure of health status and functional scales indicate better health status/function, but higher scores on symptom scales represent greater symptom severity
    European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L)
    Mean change from baseline in EQ-5D-5L visual analogue score (VAS). The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes.

    Full Information

    First Posted
    October 3, 2023
    Last Updated
    October 3, 2023
    Sponsor
    BeiGene
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06073821
    Brief Title
    Study of Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Obinutuzumab in Participants With Chronic Lymphocytic Leukemia (CLL)
    Official Title
    A Phase 3, Open-Label, Randomized Study of Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Obinutuzumab in Patients With Previously Untreated Chronic Lymphocytic Leukemia
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 1, 2023 (Anticipated)
    Primary Completion Date
    February 2032 (Anticipated)
    Study Completion Date
    December 2032 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    BeiGene

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The main objective of this study is to compare the efficacy of sonrotoclax plus zanubrutinib versus venetoclax plus obinutuzumab in participants with chronic lymphocytic leukemia (CLL)
    Detailed Description
    Chronic lymphocytic leukemia is a type of blood cancer that affects people around the world. People with CLL suffer from enlarged lymph nodes, spleen, or liver, or have symptoms like night sweats, weight loss and fever. They have shorter life expectancy compared to healthy people. There is an urgent need for new treatment to prolong participant life and control disease-related symptoms. In this study, participants with CLL, without prior treatment will receive either venetoclax plus obinutuzumab combination treatment that is considered a standard first line treatment or receive sonrotoclax plus zanubrutinib. It is hypothesized that sonrotoclax plus zanubrutinib may be better than venetoclax plus obinutuzumab in treating CLL. The main purpose of this study is to compare the duration the participants live without the CLL getting worse between participants who received venetoclax plus obinutuzumab versus sonrotoclax plus zanubrutinib. Approximately 640 participants will be included in this study around the world. Participants will have equal chance to be allocated to receive either of the treatment combinations.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    CLL
    Keywords
    CLL, Chronic Lymphocytic Leukemia

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    640 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Sonrotoclax Plus Zanubrutinib
    Arm Type
    Experimental
    Arm Description
    Participants will receive from start of Cycle 1 a standard dose of zanubrutinib once or twice daily orally and in combination with sonrotoclax starting from Cycle 4 onwards at increasing doses until target dose is reached and continuing until end of Cycle 15 (each cycle is 28 days)
    Arm Title
    Venetoclax Plus Obinutuzumab
    Arm Type
    Active Comparator
    Arm Description
    Participants will receive obinutuzumab 100mg intravenously on Day 1 Cycle 1, followed by 900 mg on Day 2 Cycle 1 (or alternatively receive 1000 mg intravenously on Day 1), followed by 1000 mg on Days 8 and 15 of Cycle 1 and thereafter on Day 1 of Cycles 2 through 6 (each cycle is 28 days) in combination with venetoclax at increasing doses until target dose is reached from Day 22 Cycle 1 until end of Cycle 12 (each cycles is 28 days)
    Intervention Type
    Drug
    Intervention Name(s)
    Sonrotoclax
    Other Intervention Name(s)
    BGB-11417
    Intervention Description
    Administered orally
    Intervention Type
    Drug
    Intervention Name(s)
    Zanubrutinib
    Other Intervention Name(s)
    BGB-3111
    Intervention Description
    Administered orally
    Intervention Type
    Drug
    Intervention Name(s)
    Venetoclax
    Intervention Description
    Administered orally
    Intervention Type
    Drug
    Intervention Name(s)
    Obinutuzumab
    Intervention Description
    Administered intravenously
    Primary Outcome Measure Information:
    Title
    Progression Free Survival (PFS)
    Description
    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 independent review committee (IRC)
    Time Frame
    Up to approximately 9 years
    Secondary Outcome Measure Information:
    Title
    Complete Response Rate (CRR)
    Description
    CRR is defined as the percentage of participants that achieved best response of complete response (CR)/ complete response with incomplete hematopoietic recovery (CRi), determined by IRC.
    Time Frame
    Up to approximately 9 years
    Title
    Rates of Undetectable Measurable Residual Disease
    Description
    Undetectable measurable residual disease uMRD4 rate at the first Post- Treatment Follow-up (PTFU 1) Visit will be based on next-generation sequencing.
    Time Frame
    Up to approximately 9 years
    Title
    Overall Survival (OS)
    Description
    OS is defined as time from the date of enrollment to the date of death because of any cause
    Time Frame
    Up to approximately 9 years
    Title
    PFS by Investigator Assessment
    Description
    FS 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 investigator assessment
    Time Frame
    Up to approximately 9 years
    Title
    CRR by Investigator Assessment
    Description
    CRR is defined as the percentage of participants that achieved best response of complete response (CR)/ complete response with incomplete hematopoietic recovery (CRi), determined by Investigator Assessment
    Time Frame
    Up to approximately 9 years
    Title
    Rates of uMRD4 Based on Flow-Cytometry
    Description
    The overall uMRD4 rate is defined as the proportion of participants who achieve uMRD status in peripheral blood before disease progression or start of new anti-CLL treatment (whichever is earlier), based on flow cytometry.
    Time Frame
    Up to approximately 9 years
    Title
    Overall Response Rate (ORR) Determined by IRC and Investigator Assessment
    Description
    ORR is defined as the percentage of participants who achieve a response (CR, CRi, nodular partial remission (nPR), partial response (PR), and partial response with lymphocytosis [PR-L]), before disease progression or start of new anti-CLL treatment (whichever is earlier).
    Time Frame
    Up to approximately 9 years
    Title
    Duration of Response (DOR) by IRC and Investigator Assessment
    Description
    Duration of response (DOR) is defined as the time from first qualifying response PR, PR-L, CR, or CRi) until CLL progression or death.
    Time Frame
    Up to approximately 9 years
    Title
    Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
    Time Frame
    Up to approximately 9 years
    Title
    The Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
    Description
    Global health status (GHS)/qualify of life (QoL) and physical functioning measured by EORTC QLQ-C30 The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 =Not at all (best) to 4 =Very Much (worst) and 2 questions answered on a 7-point scale where 1 =Very poor (worst) to 7 =Excellent (best).
    Time Frame
    Up to approximately 9 years
    Title
    HRQoL) as Assessed by EORTC QLQ-C30 CLL Module Quality of Life Questionnaire - Chronic Lymphocytic Leukemia Module 17 Items (QLQ-CLL17)
    Description
    The symptom burden and physical condition/fatigue will be measured by QLQ-CLL17. EORTC QLQ-CLL17 comprises 17 items grouped into 3 multi-item scales: 1) symptom burden, 2) physical condition/fatigue, and 3) worries/fears about health and functioning. The EORTC QLQ-CLL17 will be scored according to the EORTC QLQ-C30 Scoring Manual. An outcome variable consisting of a score from 0 to 100 will be derived for each of the symptom scales, each of the functional scales, and the global measure of health status scale. Higher scores on the global measure of health status and functional scales indicate better health status/function, but higher scores on symptom scales represent greater symptom severity
    Time Frame
    Up to approximately 9 years
    Title
    European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L)
    Description
    Mean change from baseline in EQ-5D-5L visual analogue score (VAS). The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes.
    Time Frame
    Up to approximately 9 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Treatment-naïve (TN) adults with confirmed diagnosis of CLL which requires treatment Eastern Cooperative Oncology Group (ECOG) score 0, 1, or 2 Measurable disease by Computer Tomography/Magnetic Resonance Imaging Adequate liver function as indicated by aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x the institutional upper limits of normal (ULNs) value; serum total bilirubin < 3.0 x ULN Adequate renal function as defined as creatinine clearance ≥ 50 milliliters per minute Exclusion Criteria: Previous systemic treatment for CLL Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation Known central nervous system involvement History of confirmed progressive multifocal leukoencephalopathy (PML) Uncontrolled hypertension Note: Other protocol defined criteria may apply
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Study Director
    Phone
    1-877-828-5568
    Email
    clinicaltrials@beigene.com

    12. IPD Sharing Statement

    Learn more about this trial

    Study of Sonrotoclax (BGB-11417) Plus Zanubrutinib (BGB-3111) Compared With Venetoclax Plus Obinutuzumab in Participants With Chronic Lymphocytic Leukemia (CLL)

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