Hypertension and Arrhythmias in CLL Patients Treated With BTK Inhibitors (SENTINEL)

A Prospective Longitudinal Cohort Study of the Incidence of Hypertension and Arrhythmias In Patients Treated With Bruton's Tyrosine Kinase Inhibitors For Chronic Lymphocytic Leukemia Using Wearable Technology

Acalabrutinib and Zanabrutinib are highly effective drugs used to treat Chronic Lymphocytic Leukemia, but they are associated with high blood pressure and abnormal heart rhythms. SENTINEL is an observational study that will use wearable technology to monitor heart rhythm and blood pressures at home to better understand how frequently patients are experiencing high blood pressure and/or abnormal heart rhythms.

Study Overview

• Status: Enrolling by invitation
• Conditions: Hypertension; Atrial Fibrillation; Chronic Lymphocytic Leukemia; Cardiotoxicity
• Intervention / Treatment: Other: no intervention

Detailed Description

Given the significant morbidity and mortality associated with hypertension and AF including stroke, systemic thromboembolism and heart failure, monitoring asymptomatic patients who are at high risk is an important area of investigation in the general population and is clearly an area of substantial need in the setting of BTK inhibitor use. Leveraging technology (including wearable and digital devices) to evaluate for the development of arrhythmias is an area of increasing focus in the field of cardiology and has led to various partnerships with technology companies including Apple, Google and Amazon. Several devices have shown promise in their ability to detect subclinical arrhythmias including patch and implantable recording devices, Smartwatches and digital sensors. Given the unmet need to better quantitate hypertension and arrhythmia burden in patients treated with BTK inhibitors, the investigators propose a study in which a SmartWatch, as well as at home blood pressure monitoring is used to monitor for the development of arrhythmias in either acalabrutinib- or zanubrutinib-treated CLL patients to better determine incidence and prevalence in a real world population. Based on these data, the investigators will be able to provide optimal treatment to patients while also ensuring accurate representation of hypertension and arrhythmia toxicity data which may translate into reductions in long term cardiovascular morbidity and mortality.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center at University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with Chronic Lymphocytic Leukemia initiating therapy with acalabrutinib and/or zanabrutinib will be evaluated for eligibility.

Description

Inclusion Criteria:

• Age ≥22
• Initiation of BTK inhibitor (acalabrutinib or zanubrutinib) with or without other concurrent systemic therapy as front line or relapsed/refractory therapy for chronic lymphocytic leukemia, ordered by treating oncologist per standard of care
• Normal sinus rhythm at the time of consent
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).

Exclusion Criteria:

• Current use of a class IC or III antiarrhythmic medication
• AF or other arrhythmia at the time of consent
• Uncontrolled hypertension (≥140/90mmHg) at the time of consent
• Inability to provide informed consent
• Inability to wear a watch
• Arm circumference too small (< 9 in) or arm circumference too large (> 14.5in.) to use the QardioArm cuff
• Expected survival less than one year.
• Pregnancy at time of consent
• Lack of access to a personal Apple iPhone. If the patient does not have an Apple iPhone, but another member of the patient's household has an iPhone, the patient may still be enrolled as long as there is no other Apple Watch paired with the phone.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of hypertension	New onset or worsening hypertension recorded on home blood pressure monitoring	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of atrial or ventricular arrhythmias	Any episode of atrial or ventricular arrhythmias identified via wearable device monitoring	6 months
Incident episodes of major cardiovascular events	Incident episode of stroke/TIA, other thromboembolic events, heart failure, ischemic hear events	6 months
Bruton's Tyrosine Kinase inhibitor discontinuation	determination of the rate of Bruton's Tyrosine Kinase inhibitor discontinuation after development of arrhythmia	6 months

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Investigators: Principal Investigator: Michael Fradley, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: January 9, 2024
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Actual): January 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Acalabrutinib; Zanabrutinib
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Neoplasms; Heart Diseases; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Arrhythmias, Cardiac; Hematologic Diseases; Chemically-Induced Disorders; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Hypertension; Leukemia, Lymphocytic, Chronic, B-Cell; Atrial Fibrillation; Cardiotoxicity
• Other Study ID Numbers: UPCC 43421

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No