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

• ClinicalTrials.gov Identifier: NCT02477696
• Recruitment Status: Active, not recruiting
• First Posted: June 23, 2015
• Last Update Posted: December 5, 2019
• Sponsor: Acerta Pharma BV
• Information provided by (Responsible Party): Acerta Pharma BV

Tracking Information

• First Submitted Date: June 12, 2015
• First Posted Date: June 23, 2015
• Last Update Posted Date: December 5, 2019
• Actual Study Start Date: October 2015
• Estimated Primary Completion Date: March 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 22, 2015): Progression-free survival in Arm A compared to Arm B [ Time Frame: 36 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (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 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Subjects With High Risk CLL
• Official Title: 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Chronic Lymphocytic Leukemia

Intervention

• Drug: ACP-196
• Drug: ibrutinib

Study Arms

• Experimental: acalabrutinib
  Acalabrutinib will be orally administered until disease progression or unacceptable toxicity.
  Intervention: Drug: ACP-196
• Active Comparator: ibrutinib
  Ibrutinib will be orally administered until disease progression or unacceptable toxicity.
  Intervention: Drug: ibrutinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 14, 2017): 533
• Original Estimated Enrollment (submitted: June 22, 2015): 500
• Estimated Study Completion Date: March 2021
• Estimated Primary Completion Date: March 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Denmark, France, Germany, Hungary, Israel, Italy, Netherlands, New Zealand, Poland, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT02477696
• Other Study ID Numbers: ACE-CL-006
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Acerta Pharma BV
• Study Sponsor: Acerta Pharma BV
• Collaborators: Not Provided

Investigators

• Study Director: Acerta Clinical Trials; 1-888-292-9613

• PRS Account: Acerta Pharma BV
• Verification Date: December 2019