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.