Acalabrutinib Monotherapy vs Investigator's Choice of Treatment in Patients With CL Leukaemia and Heart Failure

ConditionsChronic Lymphocytic Leukaemia Moderate to Severe Cardiac Impairment

Trial statusRecruiting

Trial phasePhase 4

Trial typeInterventional

Biological sexAll

Age18-130

SponsorAstraZeneca

About this trial

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.

Eligibility criteria

Qualifiers

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

Disqualifiers

Known active CNS leukaemia, leptomeningeal disease or spinal cord compression. In case of R/R patients with prior history of CNS localisation of leukaemia who received treatment are eligible provided that there is no evidence of CNS involvement at study entry as documented by cerebrospinal fluid (CSF) cytology and/or brain MRI.

Ongoing Richter's transformation.

Prior exposure to a BTKi.

Major surgery within 30 days before first dose of study treatment.