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: April 17, 2019
• Sponsor: Acerta Pharma BV
• Information provided by (Responsible Party): Acerta Pharma BV

Study Description

Brief Summary:

This study is designed to evaluate PFS endpoint for acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia.

Condition or disease	Intervention/treatment	Phase
Chronic Lymphocytic Leukemia	Drug: ACP-196; Drug: ibrutinib	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 533 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: June 2015
• Estimated Primary Completion Date: June 2019
• Estimated Study Completion Date: December 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Progression-free survival in Arm A compared to Arm B [ Time Frame: 36 months ]

Secondary Outcome Measures :

1. Incidence of treatment-emergent Grade ≥ 3 infections in Arm A versus Arm B [ Time Frame: 36 months ]
2. Incidence of Richter's transformation in Arm A versus Arm B [ Time Frame: 36 months ]
3. Incidence of Atrial fibrillation in Arm A versus Arm B [ Time Frame: 36 months ]
4. Overall survival in Arm A versus Arm B [ Time Frame: 36 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

  Show 160 Study Locations

Sponsors and Collaborators

Acerta Pharma BV

Investigators

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

More Information

• Responsible Party: Acerta Pharma BV
• ClinicalTrials.gov Identifier: NCT02477696 History of Changes
• Other Study ID Numbers: ACE-CL-006
• First Posted: June 23, 2015
• Last Update Posted: April 17, 2019
• Last Verified: April 2019

Additional relevant MeSH terms:

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