Observational Study of Cardiac Arrhythmias During Treatment With BTK Inhibitors or Venetoclax
- Conditions
- Waldenstr(SqrRoot)(Delta)m s MacroglobulinemiaCardiac ArrhythmiasHematologic MalignanciesMantle Cell LymphomaSudden Cardiac DeathChronic Lymphocytic Leukemia (CLL)
- Registration Number
- NCT05724121
- Brief Summary
Background:
Bruton s tyrosine kinase inhibitors (BTKi) are used to treat a form of leukemia. But taking BTKi can also increase a person s risk of developing an abnormal heart rhythm. This can cause sudden death. In this natural history study, researchers want to learn how BTKi affects the heart.
Objective:
To identify and monitor the effects of BTKi on the heart.
Eligibility:
People aged 18 and older currently receiving or planning to receive BTKi or venetoclax.
Design:
Participants who have not yet started BTKi will have 2 required clinic visits: 1 before they start taking BTKi, and 1 about 6 months later. Participants who are already taking BTKi will have 1 required visit.
Participants will undergo multiple tests:
A physical exam, including collection of blood and saliva.
A test that measures heart activity via stickers placed on the chest.
A test that uses sound waves to capture images of the heart.
An exercise stress test that monitors heart activity and blood pressure while the participant works on a treadmill or stationary bike. Sound wave images of the heart may also be taken while the participant exercises.
Stress magnetic resonance imaging (MRI) may be done in place of an exercise test. Participants will lie on a table that slides into a tube. They will be given drugs to stress the heart while images are taken.
Participants may wear a device to monitor their heart at home.
Participants may have repeat visits if they develop heart symptoms or if they need to stop taking BTKi. They will have follow-up phone calls each year for up to 3 years.
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- Detailed Description
Study Description:
Pharmacologic therapy with BTK inhibitors (BTKi) is associated with an increased risk of cardiac arrhythmias which can lead to sudden death. There is currently no standard for cardiac screening or monitoring patients on BTKi. We hypothesize that thorough and routine comprehensive cardiac evaluations prior to starting therapy with BTKi and repeated during therapy with BTKi will result in earlier identification of cardiac arrhythmias with the goal of minimizing associated morbidity and mortality. In addition, venetoclax, a different standard therapy for chronic lymphocytic leukemia, has not been associated with increased cardiac adverse events and could serve as a control group.
Objectives:
Primary objective: Identify, monitor, and analyze the arrhythmogenic effects of BTKi as well as sudden death
Secondary objective: Assess the utility of different cardiac tests for identifying and monitoring cardiac arrhythmias in patients receiving BTKi or venetoclax
Exploratory objective: To examine the relationship between the development of cardiac arrhythmias in patients on BTKi as it relates to other variables
Endpoints:
Primary endpoint:
-A composite endpoint of clinically significant cardiac arrhythmias and sudden death in patients starting a BTKi (Cohort A) and in patients already receiving BTKi (Cohort B).
Secondary endpoints:
* Detection of arrhythmias on devices (rest/stress EKG, ambulatory EKG monitor, KardiaMobile)
* Arrhythmia (treatment emergent or worsening) in patients on BTKi
* Sudden death in patients on BTKi
* A composite endpoint of clinically significant cardiac arrhythmias and sudden death in patients starting venetoclax
* Difference in cardiac arrhythmias and sudden death between different BTKi groups (e.g., ibrutinib vs. non-ibrutinib group)
* Difference in cardiac arrhythmias and sudden death between BTKi and venetoclax groups
Exploratory endpoints:
* Pharmacokinetic levels of BTKi
* Duration of BTKi exposure
* Cumulative BTKi dose
* Genetic variants
* Cardiac structural remodeling
* Medical comorbidities
* Concomitant medications
* Substance use
* Identify risk factors or biomarkers for arrhythmia
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 135
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method arrhythmogenic cardiac effects of BTKi and sudden death within the first 12 months of BTKi therapy 12 months 1. Clinically significant cardiac arrhythmias while on a BTKi (treatment emergent in those without a history of arrhythmias and worsening of arrhythmia for those with an arrhythmia at the time of enrollment testing) within 12 months. For Cohort A, if a patient has an arrhythmia at the time of baseline testing, only worsening or new arrhythmias will be called an event. For Cohort B, all arrhythmias will be called an event. 2. Sudden death
- Secondary Outcome Measures
Name Time Method tests for identifying and monitoring cardiac arrhythmias in patients receiving BTKi 36 months -Detection of arrhythmias on devices (rest EKG, stress EKG, ambulatory EKG monitor, KardiaMobile) -Clinically significant and other arrhythmias (treatment emergent or worsening) in patients on BTKi and on venetoclax -Sudden death -Composite endpoint of clinically significant cardiac arrhythmias and sudden death in patients starting venetoclax -Differences in cardiac arrhythmias and sudden death within BTKi (e.g., ibrutinib vs. non-ibrutinib group) -Differences in cardiac arrhythmias and sudden death between patients on BTKi and venetoclax
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States