Acalabrutinib Safety Study in Untreated and Relapsed or Refractory Chronic Lymphocytic Leukemia Patients

This is a global, Phase IIIb, multicenter, open-label, single-arm study to evaluate the safety and efficacy of acalabrutinib 100 mg twice daily (bid) in approximately 540 participants with chronic lymphocytic leukemia (CLL). Participants will be enrolled into 3 following cohorts: treatment-naive (TN), relapsed/refractory (R/R), and prior ibrutinib therapy. For this study, participants in the UK will be enrolled ONLY into the R/R cohort or the prior ibrutinib cohort. Participants in the US will be enrolled ONLY into the TN or R/R cohort. Participants will remain on study intervention until completion of 48 cycles (28 days per cycle), or until study intervention discontinuation due to, for example disease progression, or toxicity, withdrawal of consent, loss to follow-up, death, or study termination by the sponsor whichever occurs first. The duration of the study will be approximately 72 months from the first participant enrolled. This duration includes an estimated 24-month recruitment time and an assumed 48 cycles of study intervention (28 days per cycle); additional study time will be accrued during the Disease Follow up period for those participants remaining on study intervention after completion of 48 cycles prior to the final data cutoff (DCO) (the amount of time will vary by participant).

Inclusion Criteria: 1. Men and women ≥18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) 2. Diagnosis of CLL that meets all published diagnostic criteria (Hallek et al. 2018): 1. Monoclonal B-cells (either kappa or lambda light chain restricted) that are clonally co-expressing ≥1 B-cell marker (CD19, CD20, and CD23) and CD5 during screening 2. Prolymphocytes may comprise \80% of the total bilirubin number. The investigator must also document that hemolysis has been ruled out along with (near)-normal lactate dehydrogenase and haptoglobin 18. Estimated creatinine clearance of \ 1 week) treatment with a strong cytochrome CYP3A inhibitor/inducer. In addition, the use of strong or moderate CYP3A inhibitors or inducers within 7 days of the first dose of study intervention is prohibited.