An Open-label, Phase 2 Study of ACP-196 (Acalabrutinib) in Subjects With Mantle Cell Lymphoma

This clinical trial is a Phase 2, multicenter, (approximately 70 global centers), open-label study in subjects with histologically documented MCL, who have relapsed after, or were refractory to, ≥ 1 (but not > 5) prior treatment regimens. Subjects will be enrolled and will take 100 mg of acalabrutinib twice per day (BID) in repeated 28-day cycles.

Treatment with acalabrutinib may be continued until disease progression or an unacceptable drug-related toxicity occurs. Dose modification provisions are provided in the study protocol.

All subjects will have hematology, chemistry, and urinalysis safety panels done at screening. Once dosing commences (Day 1), all subjects will be evaluated for safety, including serum chemistry and hematology, once weekly for the first 4 weeks, every 2 weeks in Cycle 2, every 4 weeks in Cycles 3 to 12, and every 24 weeks thereafter. PK/PD testing will be done in Cycles 1 and 2. Tumor assessments will be completed at 8- to 24-week intervals during the trial.

Inclusion criteria

• Men and women ≥ 18 years of age.
• Pathologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Agreement to use contraception during the study and for 30 days after the last dose of study drugs if sexually active and able to bear or beget children.

Exclusion criteria

• A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ACP-196 (acalabrutinib), or put the study outcomes at undue risk
• Significant cardiovascular disease such as uncontrolled or symptomatic 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 corrected QT interval (QTc) > 480 msec.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
• Breast feeding or pregnant