Chronic Lymphocytic Leukemia (CLL)NCT05724121
Observational Study of Cardiac Arrhythmias During Treatment With BTK Inhibitors or Venetoclax
An observational study of Chronic Lymphocytic Leukemia (CLL) and Waldenstr(SqrRoot)(Delta)m s Macroglobulinemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 110 years
- Conditions the study is for
- Chronic Lymphocytic Leukemia (CLL), Waldenstr(SqrRoot)(Delta)m s Macroglobulinemia, Mantle Cell Lymphoma
- How many people
- 135 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2023to 8 Apr 2027
- Phase
- Observational
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 110 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Sample size of 135 subjects including men and women over 18 years old followed at the NIH Clinical Center who are either about to start a BTKi (Cohort A) or venetoclax (Cohort C) as well as those already taking BTKi (Cohort B)
Who may be able to join
- To be eligible to participate in this study, an individual must meet all of the following criteria:
- Currently receiving or planning to receive a BTKi or venetoclax.
- Male or female, aged 18 or older
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Ability of subject to understand and the willingness to sign a written informed consent document
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Any acute cardiac condition including myocardial infarction or decompensated heart failure within the past 3 months
- Pregnancy or lactation- use of BTK inhibitors is contraindicated in pregnant or nursing individuals.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
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.
Read more
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.
Read the 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
- Conditions
- Chronic Lymphocytic Leukemia (CLL), Waldenstr(SqrRoot)(Delta)m s Macroglobulinemia, Mantle Cell Lymphoma, Sudden Cardiac Death, Cardiac Arrhythmias, Hematologic Malignancies
- Keywords
- SUDDEN CARDIAC DEATH, Chronic Lymphocytic Leukemia (CLL), Ibrutinib Treatment, Atrial Fibrillation/Flutter, Ventricular Arrhythmias, Natural History
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell, Death, Sudden, Cardiac, Arrhythmias, Cardiac, Hematologic Neoplasms, Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | includes all patients prior to starting therapy with a BTKi | |
| Cohort B | includes all patients already on therapy with a BTKi | |
| Cohort C | includes all patients prior to starting therapy with venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
arrhythmogenic cardiac effects of BTKi and sudden death within the first 12 months of BTKi therapy
- 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
Measured: 12 months
Secondary outcomes (1)
tests for identifying and monitoring cardiac arrhythmias in patients receiving BTKi
-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
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2023
- Study start1 Mar 2023
- Primary completion8 Apr 2027 (estimated)
- Study completion8 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Lymphocytic Leukemia (CLL)Studies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 135 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Christine E Gruessner, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05724121
- Sponsor's protocol ID
- 10000923
- Other IDs
- 000923-H
- Status last verified
- 31 Jul 2026
- First submitted
- 10 Feb 2023
- Last updated
- 13 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No