TriangleNCT03836261 · CITED IN SOURCE DOCUMENTS
Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLL
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2024-12-27
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
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
No posted result sections were captured. Registered plans do not establish that a treatment works.
Who could take part
- eligibility Criteria
- Inclusion Criteria: * 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. Exclusion Criteria: * 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.
- healthy Volunteers
- false
- maximum Age
- 130 Years
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Acalabrutinib in combination with Venetoclax
- intervention Names
- Drug: Acalabrutinib
- Drug: Venetoclax
- label
- Acalabrutinib, Venetoclax
- type
- EXPERIMENTAL
- description
- Acalabrutinib in combination with Venetoclax with Obinutuzumab
- intervention Names
- Drug: Acalabrutinib
- Drug: Venetoclax
- Drug: Obinutuzumab
- label
- Acalabrutinib, Venetoclax, Obinutuzumab
- type
- EXPERIMENTAL
- description
- Chemoimmunotherapy FCR: Fludarabine, Cyclophosphamide and Rituximab BR: Bendamustine and Rituximab
- intervention Names
- Drug: Chemoimmunotherapy
- label
- Chemoimmunotherapy
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Acalabrutinib, Venetoclax
- Acalabrutinib, Venetoclax, Obinutuzumab
- description
- Acalabrutinib,
- name
- Acalabrutinib
- other Names
- Calquence (acalabrutinib)
- type
- DRUG
- arm Group Labels
- Acalabrutinib, Venetoclax
- Acalabrutinib, Venetoclax, Obinutuzumab
- description
- Venetoclax
- name
- Venetoclax
- other Names
- Venclyxto, Venclexta
- type
- DRUG
- arm Group Labels
- Chemoimmunotherapy
- description
- fludarabine/cyclophosphamide/rituximab (FCR), bendamustine/rituximab (BR)
- name
- Chemoimmunotherapy
- type
- DRUG
- arm Group Labels
- Acalabrutinib, Venetoclax, Obinutuzumab
- description
- Obinutuzumab
- name
- Obinutuzumab
- other Names
- Gazyva, Gazyvaro
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 984
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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
- measure
- 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
- secondary Outcomes
- description
- 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
- measure
- 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
- description
- 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
- measure
- 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
Full study description
- brief Summary
- 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
- detailed Description
- 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.
Source references
- references
- citation
- Brown JR, Seymour JF, Jurczak W, Aw A, Wach M, Illes A, Tedeschi A, Owen C, Skarbnik A, Lysak D, Eom KS, Simkovic M, Pavlovsky MA, Kater AP, Eichhorst B, Miller K, Munugalavadla V, Yu T, de Borja M, Ghia P; AMPLIFY investigators; AMPLIFY Investigators. Fixed-Duration Acalabrutinib Combinations in Untreated Chronic Lymphocytic Leukemia. N Engl J Med. 2025 Feb 20;392(8):748-762. doi: 10.1056/NEJMoa2409804. Epub 2025 Feb 5.
- pmid
- 39976417
- type
- DERIVED
- citation
- Alfaifi A, Bahashwan S, Alsaadi M, Ageel AH, Ahmed HH, Fatima K, Malhan H, Qadri I, Almehdar H. Advancements in B-Cell Non-Hodgkin's Lymphoma: From Signaling Pathways to Targeted Therapies. Adv Hematol. 2024 Nov 12;2024:5948170. doi: 10.1155/2024/5948170. eCollection 2024.
- pmid
- 39563886
- type
- DERIVED
- citation
- Davids MS, Lampson BL, Tyekucheva S, Wang Z, Lowney JC, Pazienza S, Montegaard J, Patterson V, Weinstock M, Crombie JL, Ng SY, Kim AI, Jacobson CA, LaCasce AS, Armand P, Arnason JE, Fisher DC, Brown JR. Acalabrutinib, venetoclax, and obinutuzumab as frontline treatment for chronic lymphocytic leukaemia: a single-arm, open-label, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1391-1402. doi: 10.1016/S1470-2045(21)00455-1. Epub 2021 Sep 14.
- pmid
- 34534514
- type
- DERIVED
- citation
- Gordon MJ, Danilov AV. The evolving role of Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia. Ther Adv Hematol. 2021 Jan 30;12:2040620721989588. doi: 10.1177/2040620721989588. eCollection 2021.
- pmid
- 33796237
- type
- DERIVED
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- ficacy of CALQUENCE in combination with venetoclax in previously untreated CLL patients was evaluated in AMPLIFY, a randomized, multi-center, open-label study (NCT03836261). The study included patients previously untreated for CLL without del(17p) or TP53 mutation that were 18 years of age and older. Patients were randomized to r
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Preserved source evidence · Not medical advice