Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Participants With High Risk Chronic Lymphocytic Leukemia (CLL)

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.