Chronic Lymphocytic LeukaemiaPhase 4NCT06651970
Acalabrutinib Monotherapy vs Investigator's Choice of Treatment in Patients With CL Leukaemia and Heart Failure
A Phase 4 study testing Acalabrutinib and Investigator's choice of treatment in people with Chronic Lymphocytic Leukaemia and Moderate to Severe Cardiac Impairment, run by AstraZeneca at 23 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Chronic Lymphocytic Leukaemia, Moderate to Severe Cardiac Impairment
- What is being tested?
- Acalabrutinib and Investigator's choice of treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 23 sitesin 6 countries
- Study dates
- 4 Feb 2025to 30 Sep 2032
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Treatment naïve or relapsed/refractory patients who have received no more than 2 prior lines of systemic anti-CLL treatment.
- Active disease per iwCLL 2018 criteria that requires treatment.
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- Meet the following laboratory parameters:
- Absolute neutrophil count (ANC) ≥ 500 cells/μL (0.50 × 109/L).
- Platelet count ≥ 30,000 cells/μL (30 × 109/L).
- Serum aspartate aminotransferase and ALT ≤ 3.0 × ULN.
- Total bilirubin ≤ 1.5 × ULN unless directly attributable to Gilbert's syndrome.
- Estimated creatinine clearance (ie, estimated glomerular filtration rate [eGFR] using Cockcroft-Gault) ≥ 40 mL/min, or serum creatinine ≤ 2 × ULN.
- Women and men who are sexually active and can bear children must agree to use highly effective forms of contraception while on the study and for 2 days after the last dose of acalabrutinib.
- Patients must be willing and able to adhere to the study visit schedule, understand, and comply with other protocol requirements, and provide written informed consent and authorisation to use protected health information (in accordance with national and local patient privacy regulations). Note: vulnerable patients, as defined in the ICH GCP, are not allowed on this protocol (eg, prisoners or institutionalised patients).
Who cannot join
- 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.
- Uncontrolled haemolytic anaemia.
- Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study treatment.
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- Received a live virus vaccination within 28 days of first dose of study treatment.
- History of or ongoing confirmed PML.
- History of prior malignancy except for the following:
- Prior history of malignancy with no evidence of active disease present for more than
- 3 years before screening or felt to be at low risk for recurrence by treating physician.
- Adequately treated lentigo maligna melanoma without current evidence of disease or adequately resected non-melanomatous skin cancer (ie, basal cell carcinoma or squamous cell carcinoma of the skin). (c) Curatively treated in situ carcinoma of the cervix or carcinoma in situ of the prostate at any time prior to study without current evidence of disease. 10 Unable to swallow tablets or malabsorption syndrome, or disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or gastric bypass, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
- 11 Active uncontrolled systemic infection (bacterial, fungal, viral or other) or clinically significant localised infection. 12 Known history of infection with human immunodeficiency virus (HIV). 13 Serologic status reflecting active HepB or HepC infection.
- Patients with HepB core antibody positive who are surface antigen negative or who are HepC antibody positive will need to have a negative polymerase chain reaction (PCR) result before randomisation and must be willing to undergo deoxyribonucleic acid (DNA) PCR testing during the study. (b) Patients who are HepB surface antigen positive or HepB PCR positive and those who are HepC PCR positive will be excluded. 14 History of stroke or intracranial haemorrhage within 6 months prior to randomisation.
- 15 History of bleeding diathesis (eg, haemophilia, von Willebrand disease). 16 Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study treatment. Direct anti-X (DOACs) or low molecular weight heparins (LMWH, eg, enoxaparin) on stable dosing schedule is allowed. 17 Requires treatment with a strong cytochrome P450 3A (CYP3A) inhibitor/inducer. The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks of the first dose of study treatment is prohibited. 18 Breastfeeding or pregnant. 19 Concurrent participation in another therapeutic clinical trial. 20 Uncontrolled cardiac/cardiovascular disease including the following:
- Baseline cardiac troponin (cTnI or cTnT or hs-cTn) levels greater than the upper limit of normal (per the local laboratories reference range) that is due to an acute coronary event and cannot be fully explained by non-ischaemic conditions.
- Uncontrolled cardiac tachyarrhythmias (sinus, atrial or ventricular) that require new/additional therapy within the last month.
- Clinically significant QT prolongation defined as QT interval corrected by Fridericia's formula (QTcF) values; QTcF > 500 ms.
- Any of the following within the last 3 months:
- Unstable IHD: percutaneous coronary intervention, coronary artery bypass surgery, or an episode of acute coronary syndrome including acute myocardial infarction and unstable angina pectoris. ii. Major cardiac surgery/procedures or valvular surgery. iii. Hospitalization due to heart failure. 21 Uncontrolled hypertension despite optimal management 22 Current life-threatening illness, medical conditions, organ system dysfunction or lifestyle habits which, in the investigator's opinion, could compromise the patient's safety or ability to adhere to the study protocol.
Trial locations and contacts
23 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
23 sites in 6 countries
Italy6 sites, 6 recruiting
- Recruiting
Research Site
Cagliari, 09121
- Recruiting
Research Site
Florence, 50134
- Recruiting
Research Site
Milan, 20122
- Recruiting
Research Site
Milan, 20132
- Recruiting
Research Site
Pavia, 27100
- Recruiting
Research Site
Perugia, 06156
United Kingdom6 sites, 3 recruiting
- Withdrawn
Research Site
Bournemouth, BH7 7DW
- Recruiting
Research Site
Oxford, OX3 7LE
- Recruiting
Research Site
Plymouth, PL6 8DH
- Withdrawn
Research Site
Romford, RM7 0AG
- Withdrawn
Research Site
Stockton, TS19 8PE
- Recruiting
Research Site
Sutton Coldfield, B74 3UP
United States3 sites, 2 recruiting
- Withdrawn
Research Site
Charlotte, North Carolina, 28204
- Recruiting
Research Site
Columbus, Ohio, 43210
- Recruiting
Research Site
Philadelphia, Pennsylvania, 19104
Czechia3 sites, 2 recruiting
- Recruiting
Research Site
Brno, 625 00
- Withdrawn
Research Site
Hradec Králové, 500 05
- Recruiting
Research Site
Prague, 10034
Spain3 sites, 3 recruiting
- Recruiting
Research Site
Barcelona, 08003
- Recruiting
Research Site
Madrid, 28040
- Recruiting
Research Site
Seville, 41009
Poland2 sites, 2 recruiting
- Recruiting
Research Site
Krakow, 30-727
- Recruiting
Research Site
Poznan, 60-693
About this study
Official title: 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
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.
Read the 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.
- Being tested
- Acalabrutinib, Investigator's choice of treatment
- Keywords
- Hemic Diseases, Lymphatic Diseases
- Medical subject headings
- Leukemia, B-Cell, Lymphatic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcalabrutinibDrug
Also called Calquence
Acalabrutinib Monotherapy
Investigator's choice of treatmentOther
Also called Investigator's choice of treatment : i.e venetoclax, Rituximab, Obinutuzumab, Zanubrutinib etc.
control arm treatment type will be defined by the PI prior to randomisation
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm A (Acalabrutinib Monotherapy) | Active comparator | All participants randomised to Arm A will receive treatment with the investigational product acalabrutinib. Receives: Drug: Acalabrutinib |
| Treatment Arm B | Other | Patients in Arm B will receive investigator's choice of treatment its duration will be based on standard duration of therapy for that regimen or until disease progression/patient withdrawal/study termination, whichever occurs first. Receives: Other: Investigator's choice of treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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.
Measured: 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.
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.
Measured: 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.
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
Measured: 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.
Safety endpoints 5: To evaluate the frequency of AESI per Acalabrutinib IB after acalabrutinib treatment compared to investigators choice of treatment.
Incidence and relationship to study treatment of Non-cardiovascular AE that led to discontinuation of any study treatment.
Measured: 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.
Safety endpoints 6: To evaluate the rate of discontinuation due to non-CV adverse events after acalabrutinib treatment compared to investigators choice of treatment.
Incidence and relationship to study treatment of Events of clinical interest (ECI) per acalabrutinib IB
Measured: 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.
Safety endpoints 7: To evaluate the rate of any serious adverse event after acalabrutinib treatment compared to investigators choice of treatment.
Incidence and relationship to study treatment of Serious adverse events (SAEs).
Measured: 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 (5)
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.
Measured: 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.
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).
Measured: 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.
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).
Measured: 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.
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).
Measured: 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.
Efficacy Endpoints 5:To evaluate the event free survival 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).
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2024
- Study start4 Feb 2025
- Primary completion30 Sep 2032 (estimated)
- Study completion30 Sep 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic LeukaemiaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Fortrea, CALYX Inc., eResearch Technology, Inc., CISCRP
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06651970
- Sponsor's protocol ID
- D8223C00016
- Status last verified
- Sep 2026
- First submitted
- 20 Aug 2024
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06651970
- Acronym / sponsor ID
- D8223C00016
- Keywords
- Hemic Diseases, Lymphatic Diseases
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Fortrea, CALYX Inc., eResearch Technology, Inc., CISCRP
- Study start
- 4 Feb 2025 (actual)
- Primary completion
- 30 Sep 2032 (estimated)
- Study completion
- 30 Sep 2032 (estimated)
- First posted
- 22 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm A (Acalabrutinib Monotherapy) | Active comparator | Drug: AcalabrutinibAll participants randomised to Arm A will receive treatment with the investigational product acalabrutinib. |
| Treatment Arm B | Other | Other: Investigator's choice of treatmentPatients in Arm B will receive investigator's choice of treatment its duration will be based on standard duration of therapy for that regimen or until disease progression/patient withdrawal/study termination, whichever occurs first. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
- Treatment naïve or relapsed/refractory patients who have received no more than 2 prior lines of systemic anti-CLL treatment.
Key exclusion criteria (20 listed)
- 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.
- Uncontrolled haemolytic anaemia.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcalabrutinibAlso: CalquenceAcalabrutinib Monotherapy | Drug | Treatment Arm A (Acalabrutinib Monotherapy) |
| Investigator's choice of treatmentAlso: Investigator's choice of treatment : i.e venetoclax, Rituximab, Obinutuzumab, Zanubrutinib etc.control arm treatment type will be defined by the PI prior to randomisation | Other | Treatment Arm B |
Primary outcome
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.
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.
Frequency and time to discontinuation of any study treatment due to worsening in cardiovascular function or cardiovascular AEs.
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.
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.
Incidence of Grade 4 and 5 cardiovascular events of interest.
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.
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.
Incidence and relationship to study treatment of Grade ≥ 3 AEs.
Safety endpoints 4: To evaluate the frequency of grade≥3 Adverse events after acalabrutinib treatment compared to investigators choice of treatment.
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.
Incidence and relationship to study treatment
Safety endpoints 5: To evaluate the frequency of AESI per Acalabrutinib IB after acalabrutinib treatment compared to investigators choice of treatment.
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.
Incidence and relationship to study treatment of Non-cardiovascular AE that led to discontinuation of any study treatment.
Safety endpoints 6: To evaluate the rate of discontinuation due to non-CV adverse events after acalabrutinib treatment compared to investigators choice of treatment.
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.
Incidence and relationship to study treatment of Events of clinical interest (ECI) per acalabrutinib IB
Safety endpoints 7: To evaluate the rate of any serious adverse event after acalabrutinib treatment compared to investigators choice of treatment.
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.
Incidence and relationship to study treatment of Serious adverse events (SAEs).
5 secondary outcomes
Efficacy Endpoints 1:To evaluate the overall survival after acalabrutinib treatment compared to investigators choice of treatment.
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.
Efficacy Endpoints 2:To evaluate the overall response rate after acalabrutinib treatment compared to investigators choice of treatment.
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.
Efficacy Endpoints 3: To evaluate the duration of response after acalabrutinib treatment compared to investigators choice of treatment.
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.
Efficacy Endpoints 4: To evaluate the progression free survival after acalabrutinib treatment compared to investigators choice of treatment.
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.
Efficacy Endpoints 5:To evaluate the event free survival after acalabrutinib treatment compared to investigators choice of treatment.
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2026.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
AstraZeneca Clinical Study Information Center contact
23 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Acalabrutinib and Investigator's choice of treatment in people with Chronic Lymphocytic Leukaemia and Moderate to Severe Cardiac Impairment, run by AstraZeneca at 23 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Italy, United Kingdom, United States, Czechia, Spain and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact AstraZeneca Clinical Study Information Center (1-877-240-9479, information.center@astrazeneca.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (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.). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.