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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

Sponsor
Acerta Pharma BV (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03836261
Collaborator
AstraZeneca (Industry)
780
Enrollment
202
Locations
3
Arms
94.4
Anticipated Duration (Months)
3.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
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

Study Type:
Interventional
Anticipated 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 :
Feb 25, 2019
Anticipated Primary Completion Date :
Jan 6, 2027
Anticipated Study Completion Date :
Jan 6, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: Acalabrutinib, Venetoclax

Acalabrutinib in combination with Venetoclax

Drug: Acalabrutinib
Acalabrutinib,
Other Names:
  • Calquence (acalabrutinib)

    • Drug: Venetoclax
    Venetoclax
    Other Names:
  • Venclyxto, Venclexta

    		•
    Experimental: Acalabrutinib, Venetoclax, Obinutuzumab

    Acalabrutinib in combination with Venetoclax with or without Obinutuzumab

    Drug: Acalabrutinib
    Acalabrutinib,
    Other Names:
  • Calquence (acalabrutinib)

    • Drug: Venetoclax
    Venetoclax
    Other Names:
  • Venclyxto, Venclexta

    • Drug: Obinutuzumab
    Obinutuzumab
    Other Names:
  • Gazyva, Gazyvaro

    		•
    Active Comparator: Chemoimmunotherapy

    Chemoimmunotherapy FCR: Fludarabine, Cyclophosphamide and Rituximab

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

    Outcome Measures

    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 [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 [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. [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

    Criteria

    Ages Eligible for Study:
    18 Years to 130 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 Research Site Fountain Valley California United States 92708
    2 Research Site Fullerton California United States 92835
    3 Research Site Los Angeles California United States 90095
    4 Research Site Redondo Beach California United States 90277
    5 Research Site Santa Barbara California United States 93105
    6 Research Site Orlando Florida United States 32806
    7 Research Site Fort Wayne Indiana United States 46804
    8 Research Site Wichita Kansas United States 67214
    9 Research Site Louisville Kentucky United States 40207
    10 Research Site New Orleans Louisiana United States 70056
    11 Research Site Baltimore Maryland United States 21201
    12 Research Site Boston Massachusetts United States 02215
    13 Research Site Boston Massachusetts United States 02215
    14 Research Site New York New York United States 10021
    15 Research Site New York New York United States 10032
    16 Research Site Charlotte North Carolina United States 28204
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    23 Research Site Buenos Aires Argentina 1114
    24 Research Site Buenos Aires Argentina C1426ANZ
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    34 Research Site Woolloongabba Australia 4102
    35 Research Site Krems Austria 3500
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    169 Research Site Badalona(Barcelona) Spain 08916
    170 Research Site Barcelona Spain 08035
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    172 Research Site Madrid Spain 28007
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    200 Research Site Cambridge United Kingdom CB2 0QQ
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    Sponsors and Collaborators

    • Acerta Pharma BV
    • AstraZeneca

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Acerta Pharma BV
    ClinicalTrials.gov Identifier:
    NCT03836261
    Other Study ID Numbers:
    • ACE-CL-311
    • D8221C00001
    • NCT05211856
    First Posted:
    Feb 11, 2019
    Last Update Posted:
    Aug 22, 2022
    Last Verified:
    Aug 1, 2022
    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:
    Leukemia
    Leukemia, Lymphoid
    Leukemia, Lymphocytic, Chronic, B-Cell
    Venetoclax
    Obinutuzumab
    Acalabrutinib

    Study Results

    No Results Posted as of Aug 22, 2022