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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 : November 26, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Acerta Pharma BV

Tracking Information
First Submitted Date  ICMJE February 6, 2019
First Posted Date  ICMJE February 11, 2019
Last Update Posted Date November 26, 2019
Actual Study Start Date  ICMJE February 25, 2019
Estimated Primary Completion Date August 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 8, 2019)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2019)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2019)
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 according to the iwCLL 2018 criteria:
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Acalabrutinib (ACP-196) in Combination With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus Chemoimmunotherapy for Previously Untreated CLL
Official Title  ICMJE 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
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 (30 days), treatment (from randomization until study drug discontinuation) and follow-up phase.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Lymphocytic Leukemia
Intervention  ICMJE
  • Drug: Acalabrutinib
    Acalabrutinib,
    Other Name: Calquence (acalabrutinib)
  • Drug: Venetoclax
    Venetoclax
    Other Name: Venclyxto, Venclexta
  • Drug: Chemoimmunotherapy
    fludarabine/cyclophosphamide/rituximab (FCR), bendamustine/rituximab (BR)
  • Drug: Obinutuzumab
    Obinutuzumab
    Other Name: Gazyva, Gazyvaro
Study Arms  ICMJE
  • Experimental: Acalabrutinib, Venetoclax
    Acalabrutinib in combination with Venetoclax
    Interventions:
    • Drug: Acalabrutinib
    • Drug: Venetoclax
  • Experimental: Acalabrutinib, Venetoclax, Obinutuzumab
    Acalabrutinib in combination with Venetoclax with or without Obinutuzumab
    Interventions:
    • Drug: Acalabrutinib
    • Drug: Venetoclax
    • Drug: Obinutuzumab
  • Active Comparator: Chemoimmunotherapy

    Chemoimmunotherapy

    FCR: Fludarabine, Cyclophosphamide and Rituximab

    Intervention: Drug: Chemoimmunotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 8, 2019)
780
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2024
Estimated Primary Completion Date August 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: CALL CENTER 1-888-292-9613 Acertamc@dlss.com
Listed Location Countries  ICMJE Australia,   Austria,   Bulgaria,   Canada,   Czechia,   Israel,   Italy,   Korea, Republic of,   Poland,   Russian Federation,   Saudi Arabia,   Slovakia,   South Africa,   Spain,   Sweden,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03836261
Other Study ID Numbers  ICMJE ACE-CL-311
D8221C00001 ( Other Identifier: AstraZeneca )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Acerta Pharma BV
Study Sponsor  ICMJE Acerta Pharma BV
Collaborators  ICMJE AstraZeneca
Investigators  ICMJE Not Provided
PRS Account Acerta Pharma BV
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP