RECRUITING

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

Conditions

Chronic Lymphocytic Leukaemia Heart Failure Hemic Diseases Lymphatic Diseases

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2025-02-04

Study Completion:2031-01-29

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06651970

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 130 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. Left ventricular ejection fraction assessed by ECHO \< 50%. 4. Diagnosis of CLL 5. Treatment naïve or relapsed/refractory patients who received no more than 2 prior lines of systemic anti-CLL treatment. 6. Active disease per iwCLL 2018 criteria that requires treatment. 7. Meet the following laboratory parameters: 1. Absolute neutrophil count (ANC) ≥ 500 cells/μL (0.50 × 109/L). 2. Platelet count ≥ 30,000 cells/μL (30 × 109/L). 3. Serum aspartate aminotransferase and ALT ≤ 3.0 × ULN. 4. Total bilirubin ≤ 1.5 × ULN unless directly attributable to Gilbert's syndrome. 5. Estimated creatinine clearance (ie, estimated glomerular filtration rate \[eGFR\] using Cockcroft-Gault) ≥ 40 mL/min, or serum creatinine ≤ 2 × ULN. 8. 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. 9. 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).	1. 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. 2. Ongoing Richter's transformation. 3. Prior exposure to a BTKi. 4. Major surgery within 30 days before first dose of study treatment. 5. Uncontrolled haemolytic anaemia. 6. Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study treatment. 7. Received a live virus vaccination within 28 days of first dose of study treatment. 8. History of or ongoing confirmed PML. 9. History of prior malignancy except for the following: 1. Prior history of malignancy with no evidence of active disease present for more than 1. 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. 2. 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. * Uncontrolled cardiac tachyarrhythmias (sinus, atrial or ventricular) that require new/additional therapy within the last month. * Clinically significant outlying QT interval corrected by Fridericia's formula (QTcF) values; QTcF \> 470 ms or QTcF \< 330 ms. * Unstable ischaemic heart disease (IHD), recent (\< 3 months): episode of acute coronary syndrome, including acute myocardial infarction and unstable angina pectoris. * Percutaneous coronary intervention, or coronary artery bypass graft within the last month. 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.

Inclusion Criteria

Exclusion 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. Left ventricular ejection fraction assessed by ECHO \< 50%.
4. Diagnosis of CLL
5. Treatment naïve or relapsed/refractory patients who received no more than 2 prior lines of systemic anti-CLL treatment.
6. Active disease per iwCLL 2018 criteria that requires treatment.
7. Meet the following laboratory parameters:
1. Absolute neutrophil count (ANC) ≥ 500 cells/μL (0.50 × 109/L).
2. Platelet count ≥ 30,000 cells/μL (30 × 109/L).
3. Serum aspartate aminotransferase and ALT ≤ 3.0 × ULN.
4. Total bilirubin ≤ 1.5 × ULN unless directly attributable to Gilbert's syndrome.
5. Estimated creatinine clearance (ie, estimated glomerular filtration rate \[eGFR\] using Cockcroft-Gault) ≥ 40 mL/min, or serum creatinine ≤ 2 × ULN.
8. 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.
9. 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).

1. 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.
2. Ongoing Richter's transformation.
3. Prior exposure to a BTKi.
4. Major surgery within 30 days before first dose of study treatment.
5. Uncontrolled haemolytic anaemia.
6. Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study treatment.
7. Received a live virus vaccination within 28 days of first dose of study treatment.
8. History of or ongoing confirmed PML.
9. History of prior malignancy except for the following:
1. Prior history of malignancy with no evidence of active disease present for more than
1. 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.
2. 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.
* Uncontrolled cardiac tachyarrhythmias (sinus, atrial or ventricular) that require new/additional therapy within the last month.
* Clinically significant outlying QT interval corrected by Fridericia's formula (QTcF) values; QTcF \> 470 ms or QTcF \< 330 ms.
* Unstable ischaemic heart disease (IHD), recent (\< 3 months): episode of acute coronary syndrome, including acute myocardial infarction and unstable angina pectoris.
* Percutaneous coronary intervention, or coronary artery bypass graft within the last month. 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.

Contacts and Locations

Study Contact

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479

information.center@astrazeneca.com

Study Locations (Sites)

Research Site

Charlotte, North Carolina, 28204

United States

Research Site

Columbus, Ohio, 43210

United States

Research Site

Philadelphia, Pennsylvania, 19104

United States

Collaborators and Investigators

Sponsor: AstraZeneca

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-02-04

Study Completion Date2031-01-29

Study Record Updates

Study Start Date2025-02-04

Study Completion Date2031-01-29

Terms related to this study

Keywords Provided by Researchers

Hemic Diseases
Lymphatic Diseases

Additional Relevant MeSH Terms

Chronic Lymphocytic Leukaemia
Heart Failure