A Multicentre, Open-label, Randomised Phase IV Study to Investigate Acalabrutinib Monotherapy Compared to Investigator's Choice of Treatment in Adults (> 18 Years) With Chronic Lymphocytic Leukaemia and Moderate to Severe Cardiac Impairment
This will be a global Phase IV, open-label, randomised study to evaluate the safety and tolerability of acalabrutinib (monotherapy, 100 mg orally \[po\], twice daily \[bd\]) compared to investigator's choice of treatment, in patients with CLL (TN or R/R) and moderate to severe cardiac impairment. All patients will have cardiac impairment as defined by LVEF of \< 50%. Randomisation will be stratified by LVEF \> 40% vs ≤ 40% to stratify for moderate and severe cardiac impairment, which for this study are defined as follows: Severe cardiac impairment: in those with LVEF ≤ 40% Moderate cardiac impairment: in those with LVEF \> 40% to \< 50%. The study is planned to take place in approximately 20 centres globally. The study will be conducted in centres that have established close collaboration between the Haematology and Cardiology divisions, preferably with a cardio-oncologist on the team. An IDMC will be responsible for making recommendations for study continuation.
• Men and women ≥ 18 years of age, at the time of signing the informed consent.
• Eastern Cooperative Oncology Group performance status of 0 to 3
• Left ventricular ejection fraction assessed by ECHO \< 50%.
• Diagnosis of CLL
• Treatment naïve or relapsed/refractory patients who received no more than 2 prior lines of systemic anti-CLL treatment.
• Active disease per iwCLL 2018 criteria that requires treatment.
• Meet the following laboratory parameters:
‣ Absolute neutrophil count (ANC) ≥ 500 cells/μL (0.50 × 109/L).
⁃ Platelet count ≥ 30,000 cells/μL (30 × 109/L).
⁃ Serum aspartate aminotransferase and ALT ≤ 3.0 × ULN.
⁃ Total bilirubin ≤ 1.5 × ULN unless directly attributable to Gilbert's syndrome.
⁃ Estimated creatinine clearance (ie, estimated glomerular filtration rate \[eGFR\] using Cockcroft-Gault) ≥ 40 mL/min, or serum creatinine ≤ 2 × ULN.
• Women and men who are sexually active and can bear children must agree to use highly effective forms of contraception while on the study and for 2 days after the last dose of acalabrutinib.
• Patients must be willing and able to adhere to the study visit schedule, understand, and comply with other protocol requirements, and provide written informed consent and authorisation to use protected health information (in accordance with national and local patient privacy regulations). Note: vulnerable patients, as defined in the ICH GCP, are not allowed on this protocol (eg, prisoners or institutionalised patients).