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

Prior treatment

• Ongoing AE attributed to ibrutinib therapy
• Treatment with systemic anticancer therapy for CLL is prohibited between discontinuation of ibrutinib and enrollment on this trial.
• Prior exposure to a BCL-2 inhibitor (eg, venetoclax/ABT- 199)
• History of stroke or intracranial hemorrhage within 2 months before the first dose of study drug.
• Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.
• Major surgical procedure within 28 days of first dose of study drug.
• Requires treatment with a strong CYP3A inhibitor

Other illness

• 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.
• Evidence of active Richter's transformation or any evidence of disease progression on ibrutinib therapy or any BTK inhibitor.
• Known history of human immunodeficiency virus (HIV), serologic status reflecting active hepatitis B or C infection, or any uncontrolled active systemic infection.
• Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP)
• History of bleeding diathesis.

Lab values

• 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.

Age

• 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.

Other

• CNS involvement by CLL or related Richter's transformation.

• Men and women ≥ 18 years of age.
• Prior diagnosis of CLL
• Must have received ≥ 1 prior therapy for CLL
• Intolerant of ibrutinib
• Documented disease progression after stopping ibrutinib therapy as defined by the IWCLL 2008 criteria
• Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
• ECOG performance status of ≤ 2.