The purpose of this study is to evaluate the efficacy and safety of acalabrutinib in combination with venetoclax and acalabrutinib in combination with venetoclax with and without obinutuzumab compared to chemoimmunotherapy in subjects with previously untreated CLL
This randomized, global, multicenter, open-label, Phase 3 study will evaluate the efficacy and safety of AV and AVG versus chemoimmunotherapy (FCR or BR) in subjects with previously untreated CLL without del(17p) or TP53. Subjects will be randomized in a 1:1:1 ratio into 3 arms through a block stratified randomization procedure. The study includes screening (35 days), treatment (from randomization until study drug discontinuation) and follow-up phase.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
984
Acalabrutinib,
Venetoclax
fludarabine/cyclophosphamide/rituximab (FCR), bendamustine/rituximab (BR)
To evaluate the efficacy of acalabrutinib with venetoclax (Arm A) compared to chemoimmunotherapy fludarabine/cyclophosphamide/rituximab [FCR] or bendamustine/rituximab [BR] (Arm C): PFS
Progression-free survival (PFS) after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the Independent Review Committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria
Time frame: 6 years
To evaluate the efficacy of acalabrutinib with venetoclax in combination with obinutuzumab (Arm B) compared with FCR or BR (Arm C): PFS
PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the IRC assessment and investigator assessment
Time frame: 6 years
To evaluate the efficacy of acalabrutinib with venetoclax (Arm A) compared with FCR or BR (Arm C): PFS defined the same as above per investigator assessment.
PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the IRC assessment and investigator assessment
Time frame: 6 years
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Obinutuzumab
Research Site
Los Angeles, California, United States
Research Site
Redondo Beach, California, United States
Research Site
Fort Wayne, Indiana, United States
Research Site
Wichita, Kansas, United States
Research Site
Louisville, Kentucky, United States
Research Site
New Orleans, Louisiana, United States
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Baltimore, Maryland, United States
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Boston, Massachusetts, United States
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New York, New York, United States
Research Site
Charlotte, North Carolina, United States
...and 160 more locations