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 requiringtreatment

• Must have received ≥ 1 prior therapies for CLL.

• Meet the following laboratory parameters:

• Absolute neutrophil count (ANC) ≥ 750 cells/μL or ≥ 500 cells/μL inparticipants with documented bone marrow involvement, and independent of growthfactor support 7 days before assessment.

• Platelet count ≥ 30,000 cells/μL without transfusion support 7 days beforeassessment. Participants with transfusion-dependent thrombocytopenia areexcluded.

• 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'ssyndrome.

• Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.

• Prior exposure to ibrutinib or to a B-cell receptor (BCR) inhibitor or a B-celllymphoma-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 treatedwith no evidence of active disease > 3 years before Screening and at low risk forrecurrence.

• 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 Kantagonists within 7 days of first dose of study drug.

• Requires treatment with a strong cytochrome P450 3A (CYP3A) inhibitor/inducer.