NCT06651970

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

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

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 130 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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 assessment will be performed by the PI in accordance with modified iwCLL 2018 criteria every 4 cycles (16 weeks). Imaging and BM testing only as deemed appropriate by PI. Safety assessments will be performed at every visit. Cardiology assessments will be performed at the end of cycle 1 (C2D1) and 3 (C4D1) and thereafter every 4 cycles (16 weeks). These assessments will include: * A cardiology consult. * ECHO, 12-lead ECG and 24-hour Holter. * Cardiac biomarkers. * Any additional testing will be performed as clinically indicated. Cardiac MRI post-screening will be performed every year. Decisions for permanent withdrawal or modifications to treatment due to cardiac AEs will be made by PI after close consultation with the cardiologist. Post-Treatment Phase: Safety assessments Once treatment is discontinued due to any of the reasons mentioned above, a safety follow-up (SFU) will occur within 45 days of the last dose of treatment. This will occur regardless of the patient developing progressive disease or initiation a new anti-CLL therapy during that timespan. The evaluation will include: * Cardiology consult * Cardiac biomarkers * 12-lead ECG, ECHO and 24 hour Holter * Cardiac MRI (if not performed in the last 6 months). The subsequent safety assessments will continue until disease progression, WoC, death or termination of study whichever occurs first. These will mirror the in-treatment schedule, with cardiology consults including ECHO, ECG, cardiac biomarkers and 24 hour Holter performed every 16 weeks and yearly cardiac MRI. Once patient has progressive disease they will be contacted to assess survival status every 16 weeks. Response assessments Patients that discontinue treatment prior to progression will continue to be evaluated for disease progression every 16 weeks. The response assessment will be per iwCLL 2018 guidelines and will be performed by the PI. Bone marrow testing and imaging will continue to remain optional and per PI discretion. Once patient has progressive disease they will be contacted every 16 weeks for survival status and information on any new anti-cancer therapy until WoC, death, termination of study by Sponsor whichever occurs first.

Conditions

• Chronic Lymphocytic Leukaemia
• Heart Failure

Interventions

Type	Name	Description
DRUG	Acalabrutinib	Acalabrutinib Monotherapy
OTHER	Investigator's choice of treatment	control arm treatment type will be defined by the PI prior to randomisation

Timeline

• Start date: 2025-02-04
• Primary completion: 2030-08-16
• Completion: 2030-08-16
• First posted: 2024-10-22
• Last updated: 2026-04-15

Locations

23 sites across 6 countries: United States, Czechia, Italy, Poland, Spain, United Kingdom

Regulatory

• FDA-regulated drug study