Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Participants With High Risk Chronic Lymphocytic Leukemia (CLL)
Condition: Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Acalabrutinib; Ibrutinib
Intervention description: Participants will receive oral acalabrutinib as stated in arm description.; Participants will receive oral ibrutinib as stated in arm description.
Intervention MeSH terms: Acalabrutinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 533.0
Sex: All
Healthy volunteers: No

Summary:

      This study is designed to evaluate progression-free survival (PFS) endpoint for acalabrutinib
      versus (vs) ibrutinib in previously treated chronic lymphocytic leukemia.
    

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:

               -  Absolute neutrophil count (ANC) ≥ 750 cells/μL or ≥ 500 cells/μL in participants
                  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. Participants with transfusion-dependent thrombocytopenia are
                  excluded.

               -  Serum aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase
                  (SGOT) and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase
                  (SGPT) ≤ 3.0 x upper limit of normal (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 B-cell receptor (BCR) inhibitor or a B-cell
             lymphoma-2 (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 human immunodeficiency virus (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 cytochrome P450 3A (CYP3A) inhibitor/inducer.