Acalabrutinib Monotherapy vs Investigator’s Choice of Treatment in Patients with Chronic Lymphocytic Leukaemia and Moderate to Severe Cardiac Impairment
- Conditions
- Therapeutic area: Diseases [C] - Hemic and Lymphatic Diseases [C15]Chronic Lymphocytic Leukaemia and Moderate to Severe Cardiac Impairment
- Registration Number
- CTIS2023-510147-37-00
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 55
Men and women = 18 years of age, at the time of signing the informed consent., Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3., Left ventricular ejection fraction (LVEF) assessed by echocardiogram (ECHO) < 50%., Diagnosis of CLL per (Hallek et al, 2018)., Treatment naïve (TN) or relapsed/refractory (R/R) patients who received no more than 2 prior lines of systemic anti-CLL treatment., Active disease per iwCLL 2018 (Hallek et al, 2018) criteria that requires treatment., 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 (AST) and alanine aminotransferase (ALT) = 3.0 × upper limit of normal (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 x 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 International Council for Harmonisation (ICH) Good Clinical Practice (GCP), are not allowed on this protocol (eg, prisoners or institutionalised patients).
Known active central nervous system (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 CSF cytology and/or brain MRI., 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., Active uncontrolled systemic infection (bacterial, fungal, viral, or other) or clinically significant localised infection., Known history of infection with human immunodeficiency virus (HIV)., 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 DNA PCR testing during the study. Patients who are HepB surface antigen positive or HepB PCR positive and those who are HepC PCR positive will be excluded., History of stroke or intracranial haemorrhage within 6 months prior to randomisation., History of bleeding diathesis (eg, haemophilia, von Willebrand disease)., 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., 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., Breastfeeding or pregnant., Concurrent participation in another therapeutic clinical trial., Ongoing Richter’s transformation., Uncontrolled cardiac/cardiovascular disease including the following: - 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., Uncontrolled hypertension despite optimal management., 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., 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., Received a live virus vaccination within 28 days of first dose of study treatment., History of or ongoing confirmed progressive multifocal leukoencephalopathy (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 re
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method