CLL
Conditions
Keywords
CLL, Chronic Lymphocytic Leukemia
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 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. Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
Interventions
DRUGSonrotoclax
Administered orally
DRUGZanubrutinib
Administered orally
DRUGVenetoclax
Administered orally
DRUGObinutuzumab
Administered intravenously
Sponsors
BeOne Medicines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 1: Progression Free Survival (PFS） | Up to approximately 9 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 independent review committee (IRC) |
| Cohort 1: Rate of Undetectable Measurable Residual Disease | Up to one and a half years | Undetectable measurable residual disease uMRD4 rate at the first Post- Treatment Follow-up (PTFU 1) Visit will be based on next-generation sequencing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 1: Overall Survival (OS) | Up to approximately 9 years | OS is defined as time from the date of enrollment to the date of death because of any cause |
| Cohort 1: Complete Response Rate (CRR ) by IRC | Up to approximately 9 years | 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. |
| Cohort 1: PFS by Investigator Assessment | Up to approximately 9 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 investigator assessment |
| Cohort 1: CRR by Investigator Assessment | Up to approximately 9 years | 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 |
| Cohort 1: Rate of Undetectable Measurable Residual Disease | Up to approximately 9 years | 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. |
| Cohort 1: Overall Response Rate (ORR) by IRC and Investigator Assessment | Up to approximately 9 years | 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). |
| Cohort 1: Duration of Response (DOR) by IRC and Investigator Assessment | Up to approximately 9 years | DOR is defined as the time from first qualifying response PR, PR-L, CR, or CRi) until CLL progression or death. |
| Pooled Cohorts: PFS by IRC and Investigator Assessment | Up to approximately 9 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 IRC |
| Pooled Cohorts: ORR by IRC and Investigator Assessment | Up to approximately 9 years | 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）. |
| Pooled Cohorts: DOR by IRC and Investigator Assessment | Up to approximately 9 years | DOR is defined as the time from first qualifying response PR, PR-L, CR, or CRi) until CLL progression or death. |
| Pooled Cohorts: Rate of Undetectable Measurable Residual Disease | Up to approximately 9 years | 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. |
| Pooled Cohorts: CRR by IRC and Investigator Assessment | Up to approximately 9 years | 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 |
| Cohort 1 and Pooled Cohorts: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to one and a half years for Sonrotoclax Plus Zanubrutinib group and 13 months for Venetoclax Plus Obinutuzumab group] | 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 |
| 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 | Every three cycles during the treatment period | 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. |
| 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 | Every three cycles during the treatment period | 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. |
| 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). | Every three cycles during the treatment period | 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. |
Countries
Australia, Austria, Brazil, Canada, China, Czechia, France, Germany, Israel, Italy, Japan, Netherlands, New Zealand, Poland, Puerto Rico, South Korea, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed