AstraZeneca
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.
Randomised controlled study: Treatment phase: Patients will receive treatment with either acalabrutinib 100 mg po tablets bd (until unacceptable toxicity or progression) or investigator's choice of treatment (chlorambucil, venetoclax, ibrutinib, zanabrutinib, rituximab or Obinutuzumab etc). For the control arm the treatment type and duration will be defined by the PI prior to randomisation. Each treatment cycle is 28 days/4 weeks. Haematology visits (labs, physical exam), will be performed at the first day of each cycle for the first 8 cycles and every 4 cycles there after. Response assess…
Inclusion Criteria: 1. Men and women ≥ 18 years of age, at the time of signing the informed consent. 2. Eastern Cooperative Oncology Group performance status of 0 to 3 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 coro…
Acalabrutinib Monotherapy
control arm treatment type will be defined by the PI prior to randomisation