A Study of ACP-196 (acalabrutinib) in Subjects with Relapsed/Refractory CLL and Intolerant of Ibrutinib Therapy

Exclusion Criteria

• 1. Ongoing AE attributed to ibrutinib therapy
• 2. Treatment with systemic anticancer therapy for CLL is
• prohibited between discontinuation of ibrutinib and enrollment
• on this trial.
• 3. Prior exposure to a BCL-2 inhibitor (eg, venetoclax/ABT-
• 199)
• 4. Prior malignancy (other than CLL), except for adequately
• treated basal cell or squamous cell skin cancer, in situ cancer,
• or other cancer from which the subject has been disease free
• for ≥ 2 years.
• 5. Significant cardiovascular disease such as uncontrolled or
• symptomatic untreated arrhythmias, congestive heart failure,
• or myocardial infarction within 6 months of screening, or any
• Class 3 or 4 cardiac disease as defined by the New York
• Heart Association Functional Classification, or QTc > 480
• msec at screening. Exception: Subjects with controlled,
• asymptomatic atrial fibrillation during screening are allowed
• to enroll on study.
• 6. Malabsorption syndrome, disease significantly affecting
• gastrointestinal function, resection of the stomach, extensive
• small bowel resection that is likely to affect absorption,
• symptomatic inflammatory bowel disease, partial or complete
• bowel obstruction, or gastric restrictions and bariatric surgery,
• such as gastric bypass.
• 7. Evidence of active Richter's transformation or any evidence
• of disease progression on ibrutinib therapy or any BTK
• inhibitor.
• 8. CNS involvement by CLL or related Richter’s
• transformation.
• 9. Known history of human immunodeficiency virus (HIV),
• serologic status reflecting active hepatitis B or C infection, or
• any uncontrolled active systemic infection.
• 10. Uncontrolled autoimmune hemolytic anemia (AIHA) or
• idiopathic thrombocytopenic purpura (ITP)
• 11. History of stroke or intracranial hemorrhage within 2
• months before the first dose of study drug.
• 12. History of bleeding diathesis.
• 13. Presence of a gastrointestinal ulcer diagnosed by
• endoscopy within 3 months before screening.
• 14. Major surgical procedure within 28 days of first dose of
• study drug.
• 15. Requires treatment with a strong CYP3A inhibitor