Chronic Lymphocytic Leukemia
Conditions
Keywords
B-cell Lymphoma-2 Inhibitor, Bruton Tyrosine Kinase Inhibitor
Brief summary
The purpose of this study is to investigate the efficacy and safety of fixed-duration sonrotoclax (also known as BGB-11417) plus zanubrutinib (also known as BGB-3111) (SZ) compared with fixed-duration of venetoclax plus acalabrutinib (AV) in participants with previously untreated chronic lymphocytic leukemia (CLL).
Interventions
DRUGSonrotoclax
Administered orally.
DRUGZanubrutinib
Administered orally.
DRUGAcalabrutinib
Administered orally.
DRUGVenetoclax
Administered orally.
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 bone marrow and organ function
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 or clinically significant cardiovascular disease Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) as Determined by Independent Review Committee (IRC) | Up to approximately 70 months | PFS is defined as the time from the date of randomization to the date of disease progression as determined by IRC or death due to any cause, whichever occurs first. |
| Rate of Undetectable Minimal Residual Disease at < 10^-4 sensitivity (uMRD4) | Up to approximately 16 months | Rate of uMRD4 is defined as the percentage of participants that achieved uMRD4 measured in both peripheral blood (PB) and bone marrow aspirate (BMA) at the post-treatment follow-up visit (PTFU1) based on next generation sequencing (NGS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS in High-Risk Participants | Up to approximately 70 months | PFS is defined as the time from the date of randomization to the date of disease progression as determined by IRC or death due to any cause, whichever occurs first. |
| Overall Survival (OS) | Up to approximately 70 months | OS is defined as the time from the date of randomization to the date of death due to any cause. |
| Overall Response Rate (ORR) as Determined by IRC | Up to approximately 70 months | ORR is defined as the percentage of participants with a complete response (CR), complete response with incomplete hematopoietic recovery (CRi), nodal partial response (nPR), or partial response (PR), before disease progression, death, or the start of new anti-CLL treatment (whichever is earlier), as assessed by IRC. |
| Rate of Undetectable Minimal Residual Disease at < 10^-5 sensitivity (uMRD5) | Up to approximately 16 months | Rate of uMRD5 is defined as the percentage of participants who achieved uMRD5 measured in both PB and BMA at the PTFU1 Visit based on NGS, before disease progression, death, or the start of new anti-CLL treatment (whichever is earlier). |
| Number of Participants with Adverse Events | Up to approximately 70 months | Number of participants with treatment-emergent adverse events (TEAEs), adverse events of clinical interest, and serious adverse events (SAEs), including laboratory values, vital signs, and physical examination findings. |
| PFS Determined by Investigator Assessment | Up to approximately 70 months | PFS is defined as the time from the date of randomization to the date of disease progression as determined by investigator or death due to any cause, whichever occurs first. |
| Complete Response Rate (CRR) by IRC and Investigator Assessment | Up to approximately 70 months | CRR is defined as the percentage of participants with a CR or CRi before disease progression, death, or the start of new anti-CLL treatment (whichever is earlier). |
| ORR Determined by Investigator Assessment | Up to approximately 70 months | ORR is defined as the percentage of participants with a complete response or partial response, before disease progression, death, or the start of new anti-CLL treatment (whichever is earlier), as assessed by investigator. |
| Duration of Response (DOR) | Up to approximately 70 months | Duration of response (determined by both IRC and investigator assessment) is defined as the time from the first qualifying response (CR, CRi, nPR, or PR) until CLL progression or death. DOR analysis will only include responders. |
| Time to Next Treatment (TTNT) | Up to approximately 70 months | TTNT is defined as the time from randomization to the start of the next treatment for CLL. |
| Change from Baseline in Score on European Organization for Research and Treatment of Cancer (EORTC) Item Library (IL)-409 Questionnaire | At baseline and up to approximately 70 months | Patient-reported symptoms of global health status (GHS), role functioning, and physical functioning, symptom burden and physical condition/fatigue will be measured using the European Organization for Research and Treatment of Cancer quality of life questionnaire EORTC IL-409 (an itemized version of \[EORTC\] quality of life questionnaire core 30 \[QLQ-C30\] and its CLL module CLL17). The EORTC-IL-409 consists of 17 questions answered on a 4-point scale where 1 = Not at all (best) to 4 = Very Much (worst) and 2 global health questions answered on a 7-point scale where 1 = Very poor (worst) to 7 = Excellent (best). Higher scores in GHS and functional scales and lower scores in symptom scales indicate better quality of life. |
Countries
Australia, Brazil, Canada, China, Czechia, France, Germany, Italy, Netherlands, New Zealand, Poland, Romania, South Korea, Spain, Sweden, United Kingdom, United States
Contacts
CONTACTStudy Director
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed