Cardiotoxicities in Patients Receiving BTKi

Study Overview
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Brief Summary
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This is a multicenter, prospective, observational cohort study to comprehensively and longitudinally evaluate and characterizes the cardiovascular events with CLL patients who are initiating treatment with a Bruton's tyrosine kinase (BTK) inhibitor ibrutinib or acalabrutinib.

Detailed Description
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This research study includes three visits for research blood, physical exam, and cardiac testing at baseline, 3 months, and 6 months. The study will collect the following data during the 6-month study period: Blood sample collection Electrocardiogram (ECG) Echocardiogram Cardiac magnetic resonance imaging (MRI) Mobile cardiac telemetry Blood pressure measurement

Official Title
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A Multicenter, Prospective Cohort Study for Detection of Cardiotoxicities in Patients Receiving Ibrutinib or Acalabrutinib for CLL

Conditions
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Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Intervention / Treatment
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* Diagnostic Test: Electrocardiogram
* Diagnostic Test: Echocardiogram
* Diagnostic Test: Cardiac magnetic resonance imaging
* Device: Mobile cardiac telemetry
* Diagnostic Test: Blood pressure monitoring
* Diagnostic Test: Blood draw


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Patients with confirmed diagnosis of CLL who are planned to start either ibrutinib or acalabrutinib per standard of care, in monotherapy or in combination with an anti-CD20 antibody, venetoclax, and/or a PI3K inhibitor. Both treatment-naïve and relapsed or refractory CLL are allowed. No known history of paroxysmal, persistent, or permanent atrial fibrillation. Exception: The study allows enrollment of up to 10 patients with a known history of paroxysmal atrial fibrillation (exploratory cohort). No known history chronic symptomatic congestive heart failure or documented ejection fraction < 50%. Creatinine ≤ 1.5x institutional upper limit of normal (ULN). An adequate kidney function is necessary to ensure safety of IV contrast given before cardiac MRI. Age ≥18 years. ECOG performance status ≤2 (Karnofsky ≥60%). Exclusion criteria Prior exposure to ibrutinib or acalabrutinib. Patients with a clinical contraindication to MRI. Patients with childbearing potential who cannot or do not wish to use an effective method of contraception, during the study period and for 12 months after the final treatment used for the purposes of the study. Patients with any medical condition, psychiatric condition, or social situation that in the opinion of the investigator would compromise compliance with study requirements.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Ibrutinib<br>Patients receiving ibrutinib for the treatment of CLL. | Diagnostic Test: Electrocardiogram<br>* ECG to monitor electrical activities of the heart on each visit<br>* Other names: ECG;Diagnostic Test: Echocardiogram<br>* Echocardiogram at baseline and 6 months<br>* Other names: TTE;Diagnostic Test: Cardiac magnetic resonance imaging<br>* Cardiac MRI at baseline and 6 months<br>* Other names: Cardiac MRI;Device: Mobile cardiac telemetry<br>* Mobile cardiac telemetry at baseline and 6 months<br>* Other names: Mobile telemetry;Diagnostic Test: Blood pressure monitoring<br>* Home blood pressure monitoring three times per week<br>* Other names: Home blood pressure monitoring;Diagnostic Test: Blood draw<br>* Blood draw at baseline, 3 and 6 months<br>|
| Acalabrutinib<br>Patients receiving acalabrutinib for the treatment of CLL. | Diagnostic Test: Electrocardiogram<br>* ECG to monitor electrical activities of the heart on each visit<br>* Other names: ECG;Diagnostic Test: Echocardiogram<br>* Echocardiogram at baseline and 6 months<br>* Other names: TTE;Diagnostic Test: Cardiac magnetic resonance imaging<br>* Cardiac MRI at baseline and 6 months<br>* Other names: Cardiac MRI;Device: Mobile cardiac telemetry<br>* Mobile cardiac telemetry at baseline and 6 months<br>* Other names: Mobile telemetry;Diagnostic Test: Blood pressure monitoring<br>* Home blood pressure monitoring three times per week<br>* Other names: Home blood pressure monitoring;Diagnostic Test: Blood draw<br>* Blood draw at baseline, 3 and 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of atrial arrhythmias | Any documented evidence of atrial arrhythmia including symptomatic and asymptomatic events captured by EKG, 28-day mini cardiac telemetry, or monitoring of cardiac rhythm during echocardiogram or cardiac MRI. | During 6 months of BTK inhibitor therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of ventricular arrhythmias | Assessed by 28-day mobile telemetry | During 6 months of BTK inhibitor therapy | 
| Severity of ventricular arrythmia | NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 | During 6 months of BTK inhibitor therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma