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. Patients with moderate to severe cardiac impairment will include those with moderate to severe cardiac conditions, who may have been excluded from previous acalabrutinib clinical trials and in whom the safety of acalabrutinib was not systematically assessed. The study is planned to take place in approximately 25 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
• Meet at least one of the following cardiovascular inclusion criteria: - Left ventricular ejection fraction (LVEF) \< 50% as assessed by local ECHO at screening. - History of heart failure or meeting Universal Definition of Heart Failure at screening, regardless of current LVEF. - History of ischaemic heart disease (IHD) including acute coronary syndrome, myocardial infarction, or coronary revascularization (percutaneous coronary intervention/stent or coronary artery bypass surgery). - Diagnosis of cardiomyopathy - Ongoing clinically significant (symptomatic or requiring intervention) cardiac arrhythmia, including atrial fibrillation or other arrhythmias. - History of moderate or severe cardiac valvular diseases as documented per cardiac imaging
• Diagnosis of CLL
• Treatment naïve or relapsed/refractory patients who have 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).