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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
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Acerta Pharma BV

Study Description
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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

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Acalabrutinib Drug: Venetoclax Drug: Chemoimmunotherapy Drug: Obinutuzumab Phase 3

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 780 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Acalabrutinib, Venetoclax
Acalabrutinib in combination with Venetoclax
 Drug: Acalabrutinib
Acalabrutinib,
Other Name: Calquence (acalabrutinib)

Drug: Venetoclax
Venetoclax
Other Name: Venclyxto, Venclexta
Experimental: Acalabrutinib, Venetoclax, Obinutuzumab
Acalabrutinib in combination with Venetoclax with or without Obinutuzumab
 Drug: Acalabrutinib
Acalabrutinib,
Other Name: Calquence (acalabrutinib)

Drug: Venetoclax
Venetoclax
Other Name: Venclyxto, Venclexta

Drug: Obinutuzumab
Obinutuzumab
Other Name: Gazyva, Gazyvaro
Active Comparator: Chemoimmunotherapy

Chemoimmunotherapy

FCR: Fludarabine, Cyclophosphamide and Rituximab

 Drug: Chemoimmunotherapy
fludarabine/cyclophosphamide/rituximab (FCR), bendamustine/rituximab (BR)


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Sponsors and Collaborators
Acerta Pharma BV
AstraZeneca
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Acerta Pharma BV
ClinicalTrials.gov Identifier: NCT03836261    
Obsolete Identifiers: NCT05211856
Other Study ID Numbers: ACE-CL-311
D8221C00001 ( Other Identifier: AstraZeneca )
First Posted: February 11, 2019    Key Record Dates
Last Update Posted: March 20, 2023
Last Verified: March 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Acerta Pharma BV:
CLL
Chronic Leukemia Lymphocytic
Leukemia
Additional relevant MeSH terms:
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Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
 Immune System Diseases
Leukemia, B-Cell
Venetoclax
Obinutuzumab
Acalabrutinib
Antineoplastic Agents
Antineoplastic Agents, Immunological