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Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Subjects With High Risk CLL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02477696
Recruitment Status : Active, not recruiting
First Posted : June 23, 2015
Results First Posted : January 28, 2022
Last Update Posted : June 16, 2022
Sponsor:
Information provided by (Responsible Party):
Acerta Pharma BV

Tracking Information
First Submitted Date  ICMJE June 12, 2015
First Posted Date  ICMJE June 23, 2015
Results First Submitted Date  ICMJE September 10, 2021
Results First Posted Date  ICMJE January 28, 2022
Last Update Posted Date June 16, 2022
Actual Study Start Date  ICMJE July 28, 2015
Actual Primary Completion Date September 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 27, 2022)
Progression Free Survival (PFS) by Independent Review Committee (IRC) Assessment [ Time Frame: Randomization to Disease Progression, Death, or Censoring. Assessed for up to 5 years at the time of analysis. ]
The time from date of randomization to the date of first IRC-assessed disease progression or death due to any cause. Progression by IRC is defined per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria as lymphocyte count >/= 50% from baseline; >/= 50% increase in lymph nodes, liver or spleen; >/= 50% decrease in platelets from baseline or decrease in hemoglobin > 2 g/dL from baseline and related to CLL.
Original Primary Outcome Measures  ICMJE
 (submitted: June 22, 2015)
Progression-free survival in Arm A compared to Arm B [ Time Frame: 36 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2022)
Number of Patients With Atrial Fibrillation [ Time Frame: Date of first dose until 30 days after the last dose of study drug or the start of new anticancer therapy (whichever comes first). Median follow-up was 41 months. ]
Includes MedDRA preferred terms 'atrial fibrillation' and 'atrial flutter'.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 22, 2015)
  • Incidence of treatment-emergent Grade ≥ 3 infections in Arm A versus Arm B [ Time Frame: 36 months ]
  • Incidence of Richter's transformation in Arm A versus Arm B [ Time Frame: 36 months ]
  • Incidence of Atrial fibrillation in Arm A versus Arm B [ Time Frame: 36 months ]
  • Overall survival in Arm A versus Arm B [ Time Frame: 36 months ]
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) Versus Ibrutinib in Previously Treated Subjects With High Risk CLL
Official Title  ICMJE A Randomized, Multicenter, Open-Label, Non-Inferiority, Phase III Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Subjects With High Risk Chronic Lymphocytic Leukemia
Brief Summary This study is designed to evaluate PFS endpoint for acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Chronic Lymphocytic Leukemia
Intervention  ICMJE
  • Drug: ACP-196
    acalabrutinib 100 mg BID (Arm A; N=250)
  • Drug: ibrutinib
    ibrutinib 420 mg QD (Arm B; N=250)
Study Arms  ICMJE
  • Experimental: ACP-196
    acalabrutinib 100 mg BID (Arm A; N=250)
    Intervention: Drug: ACP-196
  • Active Comparator: ibrutinib
    ibrutinib 420 mg QD (Arm B; N=250)
    Intervention: Drug: ibrutinib
Publications *

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 14, 2017)
533
Original Estimated Enrollment  ICMJE
 (submitted: June 22, 2015)
500
Estimated Study Completion Date  ICMJE August 31, 2027
Actual Primary Completion Date September 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Men and women ≥ 18 years of age.
  • ECOG performance status of 0 to 2.
  • Diagnosis of CLL.
  • Must have ≥ 1 of the following high-risk prognostic factors:

    • Presence of 17p del by central laboratory.
    • Presence of 11q del by central laboratory.
  • Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring treatment
  • Must have received ≥ 1 prior therapies for CLL.
  • Meet the following laboratory parameters:

    • ANC ≥ 750 cells/μL or ≥ 500 cells/μL in subjects with documented bone marrow involvement, and independent of growth factor support 7 days before assessment.
    • Platelet count ≥ 30,000 cells/μL without transfusion support 7 days before assessment. Subjects with transfusion-dependent thrombocytopenia are excluded.
    • Serum AST/SGOT and ALT/SGPT ≤ 3.0 x ULN.
    • Total bilirubin ≤ 1.5 x ULN.
    • Estimated creatinine clearance ≥ 30 mL/min.

Exclusion Criteria:

  • Known CNS lymphoma or leukemia.
  • Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome.
  • Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
  • Prior exposure to ibrutinib or to a BCR inhibitor or a BCL-2 inhibitor.
  • Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days before first dose of study drug.
  • Prior radio- or toxin-conjugated antibody therapy.
  • Prior allogeneic stem cell or autologous transplant.
  • Major surgery within 4 weeks before first dose of study drug.
  • Prior malignancy, except for adequately treated lentigo maligna melanoma, non-melanomatous skin cancer, in situ cervical carcinoma or other malignancy treated with no evidence of active disease > 3 years before Screening and at low risk for recurrence.
  • Significant cardiovascular disease within 6 months of screening.
  • Known history of infection with HIV.
  • History of stroke or intracranial hemorrhage within 6 months before randomization.
  • History of bleeding diathesis.
  • Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists within 7 days of first dose of study drug.
  • Requires treatment with a strong CYP3A inhibitor/inducer.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Denmark,   France,   Germany,   Hungary,   Israel,   Italy,   Netherlands,   New Zealand,   Poland,   Spain,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02477696
Other Study ID Numbers  ICMJE ACE-CL-006
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Current Responsible Party Acerta Pharma BV
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Acerta Pharma BV
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Acerta Clinical Trials 1-888-292-9613
PRS Account Acerta Pharma BV
Verification Date May 2022

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