Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Subjects With High Risk 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:

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.