Ignite Creation Date:
2024-10-26 @ 3:43 PM
Last Modification Date:
2024-10-26 @ 3:43 PM
Study NCT ID:
NCT06651970
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-20
Brief Title:
Acalabrutinib Monotherapy vs Investigators Choice of Treatment in Patients With CL Leukaemia and Heart Failure
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Multicentre Open-label Randomised Phase IV Study to Investigate Acalabrutinib Monotherapy Compared to Investigators Choice of Treatment in Adults 18 Years With Chronic Lymphocytic Leukaemia and Moderate to Severe Cardiac Impairment
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 investigators choice of treatment in patients with CLL TN or RR 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
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 investigators 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 days4 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
Treatment phase
Patients will receive treatment with either acalabrutinib 100 mg po tablets bd until unacceptable toxicity or progression or investigators 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 days4 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None