Acalabrutinib Monotherapy vs Investigator's Choice of Treatment in Patients With CL Leukaemia and Heart Failure
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. 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Acalabrutinib
DrugAcalabrutinib Monotherapy
Investigator's choice of treatment
Other interventioncontrol arm treatment type will be defined by the PI prior to randomisation
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: Treatment Arm A (Acalabrutinib Monotherapy)Active comparator 1 intervention
Group B: Treatment Arm BOther 1 intervention
Trial outcomes
Primary outcomes
1
Safety endpoints 1: To evaluate the incidence of CV (CardioVascular) adverse events leading to drug discontinuation after acalabrutinib treatment compared to investigators choice of treatment.
Frequency and time to discontinuation of any study treatment due to worsening in cardiovascular function or cardiovascular AEs.
Time frame
Visits are screening+ 8 visits( every 4 weeks) and then every 16 weeks until termination of the study which would be 4 years from the last subject randomized.2
Safety endpoints 2: To evaluate the duration on treatment prior to drug discontinuation due to CV adverse events after acalabrutinib treatment compared to investigators choice of treatment.
Incidence of Grade 4 and 5 cardiovascular events of interest.
Time frame
Visits are screening+ 8 visits( every 4 weeks) and then every 16 weeks until termination of the study which would be 4 years from the last subject randomized.3
Safety endpoints 3: To evaluate the incidence of life threatening and fatal cardiac events of interest after acalabrutinib treatment compared to investigators choice of treatment.
Incidence and relationship to study treatment of Grade ≥ 3 AEs.
Time frame
Visits are screening+ 8 visits( every 4 weeks) and then every 16 weeks until termination of the study which would be 4 years from the last subject randomized.4
Safety endpoints 4: To evaluate the frequency of grade≥3 Adverse events after acalabrutinib treatment compared to investigators choice of treatment.
Incidence and relationship to study treatment of Adverse events of special interest (AESI) defined per Acalabrutinib IB
Time frame
Visits are screening+ 8 visits( every 4 weeks) and then every 16 weeks until termination of the study which would be 4 years from the last subject randomized.Secondary outcomes
1
Efficacy Endpoints 1:To evaluate the overall survival after acalabrutinib treatment compared to investigators choice of treatment.
Overall survival (OS), defined as the time from randomisation to death from any cause. Per iwCLL 2018 criteria: • Event-free survival (EFS), defined as the time from randomisation to disease progression, initiation of subsequent anti-CLL therapy, or death from any cause, whichever occurs first.
Time frame
Visits are screening+ 8 visits( every 4 weeks) and then every 16 weeks until termination of the study which would be 4 years from the last subject randomized.2
Efficacy Endpoints 2:To evaluate the overall response rate after acalabrutinib treatment compared to investigators choice of treatment.
Overall response rate (ORR), defined as the proportion of patients with a complete response (CR), complete response with incomplete bone marrow recovery (CRi), nodular partial response (nPR) or partial response (PR).
Time frame
Visits are screening+ 8 visits( every 4 weeks) and then every 16 weeks until termination of the study which would be 4 years from the last subject randomized.3
Efficacy Endpoints 3: To evaluate the duration of response after acalabrutinib treatment compared to investigators choice of treatment.
Duration of response (DOR), defined as the time from the first documented response (PR or better) to disease progression or death (by any cause in the absence of disease progression).
Time frame
Visits are screening+ 8 visits( every 4 weeks) and then every 16 weeks until termination of the study which would be 4 years from the last subject randomized.4
Efficacy Endpoints 4: To evaluate the progression free survival after acalabrutinib treatment compared to investigators choice of treatment.
Progression-free survival (PFS), defined as the time from randomisation to disease progression or death (by any cause in the absence of disease progression).
Time frame
Visits are screening+ 8 visits( every 4 weeks) and then every 16 weeks until termination of the study which would be 4 years from the last subject randomized.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
AstraZeneca
Lead sponsor
Fortrea
Collaborator
CALYX Inc.
Collaborator
eResearch Technology, Inc.
Collaborator
CISCRP
Collaborator
Source ClinicalTrials.gov