A Study About How Blood Cell Growth Patterns Relate to Heart Health After Treatment for Hodgkin Lymphoma

Recruiting

• Conditions: Cardiovascular Disorder; Hodgkin Lymphoma; Clonal Hematopoiesis
• Interventions: Procedure: Biospecimen Collection; Other: Electronic Health Record Review; Procedure: Magnetic Resonance Imaging; Other: Survey Administration

• Registration Number: NCT05705531
• Lead Sponsor: Children's Oncology Group

Brief Summary

This study assesses how blood cell growth patterns (clonal hematopoiesis), relates to heart health or cardiovascular disease (CVD) after treatment in patients with Hodgkin lymphoma. In some patients, cancer treatment at a young age may lead to later complications, including problems with heart health. Checking for blood cell growth patterns called therapy-related clonal hematopoiesis (t-CH) can help predict who might be at risk for heart health problems after Hodgkin lymphoma treatment. If doctors know who may be at greater risk for developing later heart complications, then they can more closely monitor those patients to prevent or detect heart complications early.

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the prevalence of participants in AHOD1331 with therapy-related clonal hematopoiesis (t-CH) possessing somatic mutations associated with cardiovascular disease (CVD) which are detected after Hodgkin Lymphoma therapy.

II. To assess participants of AHOD1331 with t-CH for the presence or absence of objective signs of CVD using cardiac magnetic resonance imaging (MRI).

SECONDARY OBJECTIVES:

I. To assess whether participants in AHOD1331 with t-CH expand this population over time and possess objective findings of CVD.

II. To assess whether patients both with and without objective findings of CVD using cardiac MRI possess clinical risk factors for CVD.

EXPLORATORY OBJECTIVES:

I. To assess the prevalence of patients receiving mediastinal radiation who have objective findings of CVD using cardiac MRI, that also possess t-CH with mutations associated with CVD.

II. To assess whether specific patient characteristics and treatment (age, gender, race, dexrazoxane usage, etc.) correlate with a higher incidence of t-CH with mutations associated with CVD.

III. To assess the effects of t-CH on CVD by considering other factors such as patient characteristics and clinical conditions associated with an elevated risk for CVD.

OUTLINE: This is an observational study.

Patients undergo collection of blood samples, complete surveys, and undergo cardiac MRI on study. Patients also have their medical records reviewed.

Study Timeline

• Study First Submitted: 2023-01-11
• Study First Submitted QC: 2023-01-20
• Study First Posted: 2023-01-30
• Study Start: 2023-08-18
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-11
• Last Update Posted: 2025-02-13
• Primary Completion: 2028-10-01
• Study Completion: 2028-10-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 230

Inclusion Criteria

• Patient must be >= 7 years of age at the time of enrollment (age to perform an MRI without sedation).
• Enrolled and completed therapy on AHOD1331.
• Not known to have had a primary event (relapse/second malignancy/death). Note: Subjects enrolled and/or treated on AHOD1331 at another institution are eligible if they are now being followed at the current Children's Oncology Group (COG) institution.
• Patient must have access to cardiac MRI at institution where receiving follow-up care and must be able to complete cardiac MRI without sedation.
• All patients and/or their parents or legal guardians must sign a written informed consent.
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria

• Medical contraindication to undergoing a cardiac MRI.
• Removed from AHOD1331 therapy prior to completing the AHOD1331 protocol specified treatment plan.
• Received cancer therapy in addition to that of AHOD1331 (e.g., for disease progression or recurrence, or subsequent malignant neoplasm).
• History of cardiovascular disease prior to enrollment on AHOD1331.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Observational (blood samples, surveys, MRI, record review)	Biospecimen Collection	Patients undergo collection of blood samples, complete surveys, and undergo cardiac MRI on study. Patients also have their medical records reviewed.
Observational (blood samples, surveys, MRI, record review)	Electronic Health Record Review	Patients undergo collection of blood samples, complete surveys, and undergo cardiac MRI on study. Patients also have their medical records reviewed.
Observational (blood samples, surveys, MRI, record review)	Magnetic Resonance Imaging	Patients undergo collection of blood samples, complete surveys, and undergo cardiac MRI on study. Patients also have their medical records reviewed.
Observational (blood samples, surveys, MRI, record review)	Survey Administration	Patients undergo collection of blood samples, complete surveys, and undergo cardiac MRI on study. Patients also have their medical records reviewed.

Primary Outcome Measures

Name	Time	Method
Proportion of therapy-related clonal hematopoiesis (t-CH) for patients with cardiovascular disease (CVD) after Hodgkin Lymphoma therapy	Up to 1 year	The proportions will be compared with one-sided Z-Test with normal approximation and significance level 0.05 for primary.
Objective signs of CVD	Up to 1 year	Left Ventricular End Diastolic Volume indexed to body surface are (LVEDVi) \> 85 mL:/meter\^2.
Proportion of t-CH with mutations for patients with CVD after Hodgkin Lymphoma therapy	Up to 1 year	The proportions of t-CH mutation for patients without CVD after Hodgkin Lymphoma therapy. The proportions will be compared with one-sided Z-Test with normal approximation and significance level 0.05 for primary.
Proportion of t-CH for patients without CVD after Hodgkin Lymphoma therapy	Up to 1 year	The proportions will be compared with one-sided Z-Test with normal approximation and significance level 0.05 for primary.
Proportion of t-CH with mutations for patients without CVD after Hodgkin Lymphoma therapy	Up to 1 year	The proportions will be compared with one-sided Z-Test with normal approximation and significance level 0.05 for primary.

Secondary Outcome Measures

Name	Time	Method
Association between the presence of CVD and individual variables	Up to 1 year	The outcome is the presence of CVD. This aim is to determine if there is an association between the presence of CVD and the individual variables constituting the clinical profile, either parametric (e.g., independent t-test, Chi\^2-test, Pearson correlation coefficients) or nonparametric (e.g., Wilcoxon rank sum tests, Spearman's rank correlation coefficients) methods will be applied. Bootstrapping techniques might be used as a method of inference which does not rely on a specific underlying distribution. The statistical significance level will be set to 0.05 and all data analysis will be done using SAS statistical software (version 9.4).
Expansion of CH	Up to 1 year	The outcome is the expansion of the CH, which will be expressed as the variant allele fraction (VAF) (CH verses the total normal DNA in the sample). Graphic analysis to reveal the time varying trend in the association between the expansion of CH over time and the presence/worsening of CVD signs and apply generalized estimating equation method (with each patient as cluster unit) to quantify this association while controlling for the potential correlation of repeated measurements within each patient.

Trial Locations

Locations (23)

USA Health Strada Patient Care Center; 🇺🇸 Mobile, Alabama, United States

Phoenix Childrens Hospital; 🇺🇸 Phoenix, Arizona, United States

Alfred I duPont Hospital for Children; 🇺🇸 Wilmington, Delaware, United States

Golisano Children's Hospital of Southwest Florida; 🇺🇸 Fort Myers, Florida, United States

Arnold Palmer Hospital for Children; 🇺🇸 Orlando, Florida, United States

Saint Joseph's Hospital/Children's Hospital-Tampa; 🇺🇸 Tampa, Florida, United States

C S Mott Children's Hospital; 🇺🇸 Ann Arbor, Michigan, United States

Children's Hospitals and Clinics of Minnesota - Minneapolis; 🇺🇸 Minneapolis, Minnesota, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

Albany Medical Center; 🇺🇸 Albany, New York, United States

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

Wake Forest University Health Sciences; 🇺🇸 Winston-Salem, North Carolina, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States

East Tennessee Childrens Hospital; 🇺🇸 Knoxville, Tennessee, United States

Cook Children's Medical Center; 🇺🇸 Fort Worth, Texas, United States

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center; 🇺🇸 Houston, Texas, United States

Children's Hospital of San Antonio; 🇺🇸 San Antonio, Texas, United States

Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada