Elevate CLL R/R: Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Subjects With High Risk Chronic Lymphocytic Leukemia

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.