Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLL
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|ClinicalTrials.gov Identifier: NCT03836261|
Recruitment Status : Recruiting
First Posted : February 11, 2019
Last Update Posted : March 20, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia||Drug: Acalabrutinib Drug: Venetoclax Drug: Chemoimmunotherapy Drug: Obinutuzumab||Phase 3|
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 (Clinical Trial)|
|Estimated Enrollment :||780 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized, Multicenter, Open-Label, Phase 3 Study to Compare the Efficacy and Safety of Acalabrutinib (ACP-196) in Combination With Venetoclax With and Without Obinutuzumab Compared to Investigator's Choice of Chemoimmunotherapy in Subjects With Previously Untreated Chronic Lymphocytic Leukemia Without Del(17p) or TP53 Mutation|
|Actual Study Start Date :||February 25, 2019|
|Estimated Primary Completion Date :||January 6, 2027|
|Estimated Study Completion Date :||January 6, 2027|
Experimental: Acalabrutinib, Venetoclax
Acalabrutinib in combination with Venetoclax
Other Name: Calquence (acalabrutinib)
Other Name: Venclyxto, Venclexta
Experimental: Acalabrutinib, Venetoclax, Obinutuzumab
Acalabrutinib in combination with Venetoclax with or without Obinutuzumab
Other Name: Calquence (acalabrutinib)
Other Name: Venclyxto, Venclexta
Other Name: Gazyva, Gazyvaro
Active Comparator: Chemoimmunotherapy
FCR: Fludarabine, Cyclophosphamide and Rituximab
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 [ Time Frame: 6 years ]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
- To evaluate the efficacy of acalabrutinib with venetoclax in combination with obinutuzumab (Arm B) compared with FCR or BR (Arm C): PFS [ Time Frame: 6 years ]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
- 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. [ Time Frame: 6 years ]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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years to 130 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Men and women ≥18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Diagnosis of CLL that meets published diagnostic criteria (Hallek et al. 2018)
- Active disease per IWCLL 2018 criteria that requires treatment.
- Participants must use highly effective birth control throughout the study.
- Any prior CLL-specific therapies.
- Detected del(17p) or TP53 mutation.
- Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (e.g., Richter's transformation, prolymphocytic leukemia [PLL], or diffuse large B cell lymphoma [DLBCL]), or central nervous system (CNS) involvement by leukemia.
- History of confirmed progressive multifocal leukoencephalopathy (PML).
- Received any investigational drug within 30 days before first dose of study drug.
- Major surgical procedure within 30 days before the first dose of study drug.
- Significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 or 4 cardiac disease. Note: Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study.
- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach, or extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
- Received a live virus vaccination within 28 days of first dose of study drug.
- Known history of infection with human immunodeficiency virus (HIV).
- Serologic status reflecting active hepatitis B or C infection.
- History of known hypersensitivity or anaphylactic reactions to study drugs or excipients.
- History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.
- Known bleeding disorders.
- Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
- Female participants must not be breastfeeding or pregnant.
- Concurrent participation in another therapeutic clinical trial.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03836261
|Contact: AstraZeneca Clinical Study Information Centerfirstname.lastname@example.org|
|Responsible Party:||Acerta Pharma BV|
|Other Study ID Numbers:||
D8221C00001 ( Other Identifier: AstraZeneca )
|First Posted:||February 11, 2019 Key Record Dates|
|Last Update Posted:||March 20, 2023|
|Last Verified:||March 2023|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Chronic Leukemia Lymphocytic
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Immune System Diseases
Antineoplastic Agents, Immunological