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)
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 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 sonrotoclax plus zanubrutinib versus venetoclax plus obinutuzumab. Approximately 652 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
652
Administered orally
Administered orally
Administered orally
Cohort 1: 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)
Time frame: Up to approximately 9 years
Cohort 1: Rate 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.
Time frame: Up to one and a half years
Cohort 1: Complete Response Rate (CRR ) by IRC
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
Cohort 1: Overall Survival (OS)
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
Cohort 1: PFS by Investigator Assessment
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 investigator assessment
Time frame: Up to approximately 9 years
Cohort 1: 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
Time frame: Up to approximately 9 years
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Administered intravenously
Alaska Oncology and Hematology, Llc
Anchorage, Alaska, United States
City of Hope National Medical Center
Duarte, California, United States
University of California San Diego (Ucsd) Moores Cancer Center
La Jolla, California, United States
Valkyrie Clinical Trials
Los Angeles, California, United States
UCLA Department of Medicine Hematologyoncology
Los Angeles, California, United States
Chao Family Comprehensive Cancer Center
Orange, California, United States
Stanford Medicine
Palo Alto, California, United States
University of Colorado Cancer Center
Aurora, Colorado, United States
Medstar Georgetown University Hospital
Washington D.C., District of Columbia, United States
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States
...and 192 more locations
Cohort 1: Rate of Undetectable Measurable Residual Disease
The overall uMRD4 rate is defined as the percentage 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
Cohort 1: Overall Response Rate (ORR) 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).
Time frame: Up to approximately 9 years
Cohort 1: Duration of Response (DOR) by IRC and Investigator Assessment
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
Pooled Cohorts: PFS by IRC and Investigator Assessment
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 IRC
Time frame: Up to approximately 9 years
Pooled Cohorts: ORR 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）.
Time frame: Up to approximately 9 years
Pooled Cohorts: DOR by IRC and Investigator Assessment
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
Pooled Cohorts: Rate of Undetectable Measurable Residual Disease
The overall uMRD4 rate is defined as the percentage of participants who achieve uMRD status in peripheral blood before disease progression or start of new anti-CLL treatment (whichever is earlier),based on next-generation sequencing.
Time frame: Up to approximately 9 years
Pooled Cohorts: CRR by IRC and 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
Time frame: Up to approximately 9 years
Cohort 1 and Pooled Cohorts: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Safety will be assessed by monitoring and recording of all treatment emergent adverse events (AEs) graded by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0
Time frame: Up to one and a half years for Sonrotoclax Plus Zanubrutinib group and 13 months for Venetoclax Plus Obinutuzumab group]
Cohort 1 and Pooled Cohorts: Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Questionnaire -Core 30 (EORTC QLQ-C30) Global Health Status/QoL (GHS) and Physical Functioning Scales
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). Higher scores in GHS and functional scales indicate better quality of life.
Time frame: Every three cycles during the treatment period
Cohort 1 and Pooled Cohorts: Change from baseline in EORTC Quality of Life Questionnaire - Chronic Lymphocytic Leukemia Module 17 Items (QLQ-CLL17) Symptom Burden and Physical Condition Scales
The symptom burden and physical condition/fatigue will be measured by EQ-5D-5L. EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ visual analogue scale (VAS). EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Number of participants with various responses to the mobility questionnaire are reported.
Time frame: Every three cycles during the treatment period
Cohort 1 and Pooled Cohorts: Change from baseline in European Quality of Life 5-Dimensions 5-Levels Health Questionnaire （EQ-5D-5L) Visual Analogue Scale (VAS).
Mean change from baseline in EQ-5D-5L 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: Every three cycles during the treatment period