A Study of Acalabrutinib vs Investigator's Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in R/R CLL

Inclusion Criteria:

- Men and women ≥ 18 years of age.

- ECOG performance status of 0 to 2.

- Received ≥ 1 prior systemic therapies for CLL.

- Diagnosis of CLL - CD-20 positive, and meeting published criteria (Hallek, 2008).

- Active disease meeting ≥ 1 of the IWCLL 2008 criteria for requiring treatment.

- 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 ≥ 50,000 cells/μL or ≥ 30,000 cells/μL in subjects with documented
bone marrow involvement, and without transfusion support 7 days before
assessment.

- AST and ALT ≤ 2.0 x upper limit of normal

- Total bilirubin ≤ 1.5 x ULN.

- Estimated creatinine clearance of ≥ 30 mL/min

Exclusion Criteria:

- Known prolymphocytic leukemia or history of, or currently suspected, Richter's
syndrome. Known CNS lymphoma or leukemia.

- Prior exposure to a BCL-2 inhibitor or B-cell receptor inhibitor.

- Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura.

- 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.

- Major surgery within 30 days of first dose of study drug.

- Prior malignancy, except for adequately treated lentigo maligna melanoma,
non-melanomatous skin cancer, carcinoma in situ or other malignancy treated with no
evidence of active disease > 2 years before Screening and at low risk for recurrence.

- Significant cardiovascular disease within 6 months of screening.

- Known history of infection with HIV, or any uncontrolled active systemic infection.

- Active CMV infection.

- Serologic status reflecting active hepatitis B or C infection.

- History of or ongoing drug-induced pneumonitis.

- Malabsorption syndrome, or other condition that would impair absorption of oral study
medication.

- Received a live virus vaccination within 28 days of first dose of study drug.

- History of stroke or intracranial hemorrhage within 6 months before first dose of
study drug.

- 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.