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

May 1, 2026 updated by: Children's Oncology Group

Assessment of Clonal Hematopoiesis and Its Relationship to Cardiovascular Disease in Hodgkin Lymphoma Survivors

This study assesses how blood cell growth patterns (clonal hematopoiesis) relate 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the prevalence of therapy-related clonal hematopoiesis (t-CH) possessing somatic mutations associated with cardiovascular disease (CVD) in anthracycline exposed pediatric classical Hodgkin Lymphoma patients detected after front line Hodgkin Lymphoma therapy.

II. To compare rates of t-CH possessing somatic mutations associated with CVD between anthracycline exposed pediatric classical Hodgkin Lymphoma patients with versus without objective signs of CVD according to cardiac magnetic resonance imaging (MRI).

SECONDARY OBJECTIVES:

I. To evaluate whether the incidence of t-CH possessing somatic mutations associated with CVD increases over time among pediatric classical Hodgkin Lymphoma patients previously treated with anthracyclines.

II. To compare rates of objective findings of CVD between groups of anthracycline exposed pediatric classical Hodgkin Lymphoma patients with versus without clinical risk factors for CVD.

EXPLORATORY OBJECTIVES:

I. To compare the prevalence of t-CH with mutations associated with CVD between anthracycline exposed pediatric classical Hodgkin Lymphoma patients who received versus did not receive mediastinal radiation as part of their initial treatment.

II. To assess whether specific patient characteristics and other treatment components (age, sex, race, dexrazoxane usage, etc.) are associated with an increased likelihood of t-CH with mutations associated with CVD.

III. To evaluate the effect of t-CH with mutations associated with CVD on objective findings of CVD, as adjusted for or mediated by 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 and may have archived blood samples collected if available.

Study Type

Observational

Enrollment (Estimated)

190

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Suspended
        • Hospital for Sick Children
  • United States
    • Alabama
      • Mobile, Alabama, United States, 36604
        • Recruiting
        • USA Health Strada Patient Care Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-388-8721
        • Principal Investigator:
          • Hamayun Imran
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Recruiting
        • Phoenix Childrens Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 602-546-0920
        • Principal Investigator:
          • Alexandra M. Walsh
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Saro H. Armenian
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Recruiting
        • Connecticut Children's Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 860-545-9981
        • Principal Investigator:
          • Michael S. Isakoff
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale University
        • Contact:
        • Principal Investigator:
          • Rozalyn L. Rodwin
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Recruiting
        • Alfred I duPont Hospital for Children
        • Contact:
        • Principal Investigator:
          • Emi H. Caywood
    • Florida
      • Fort Myers, Florida, United States, 33908
        • Recruiting
        • Golisano Children's Hospital of Southwest Florida
        • Contact:
        • Principal Investigator:
          • Emad K. Salman
      • Orlando, Florida, United States, 32806
        • Recruiting
        • Arnold Palmer Hospital for Children
        • Principal Investigator:
          • Jaime M. Libes-Bander
        • Contact:
      • Tampa, Florida, United States, 33607
        • Recruiting
        • Saint Joseph's Hospital/Children's Hospital-Tampa
        • Contact:
        • Principal Investigator:
          • Don E. Eslin
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Recruiting
        • Children's Healthcare of Atlanta - Arthur M Blank Hospital
        • Principal Investigator:
          • Karen E. Effinger
        • Contact:
    • Illinois
      • Springfield, Illinois, United States, 62702
        • Recruiting
        • Southern Illinois University School of Medicine
        • Contact:
          • Site Public Contact
          • Phone Number: 217-545-7929
        • Principal Investigator:
          • Gregory P. Brandt
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland/Greenebaum Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-888-8823
        • Principal Investigator:
          • Teresa A. York
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • C S Mott Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 800-865-1125
        • Principal Investigator:
          • Jennifer E. Agrusa
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Recruiting
        • Children's Hospitals and Clinics of Minnesota - Minneapolis
        • Principal Investigator:
          • Michael K. Richards
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
        • Principal Investigator:
          • Robert J. Hayashi
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Recruiting
        • Hackensack University Medical Center
        • Principal Investigator:
          • Katharine R. Lange
        • Contact:
          • Site Public Contact
          • Phone Number: 551-996-2897
    • New York
      • Albany, New York, United States, 12208
        • Recruiting
        • Albany Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 518-262-5513
        • Principal Investigator:
          • Lauren R. Weintraub
      • Buffalo, New York, United States, 14263
        • Recruiting
        • Roswell Park Cancer Institute
        • Contact:
        • Principal Investigator:
          • Kara M. Kelly
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest University Health Sciences
        • Contact:
          • Site Public Contact
          • Phone Number: 336-713-6771
        • Principal Investigator:
          • Sarah Supples
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital Medical Center
        • Contact:
        • Principal Investigator:
          • Jonathan D. Bender
      • Columbus, Ohio, United States, 43205
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health and Science University
        • Contact:
        • Principal Investigator:
          • Susan J. Lindemulder
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia
        • Contact:
        • Principal Investigator:
          • Sogol Mostoufi-Moab
      • Pittsburgh, Pennsylvania, United States, 15224
        • Recruiting
        • Children's Hospital of Pittsburgh of UPMC
        • Contact:
        • Principal Investigator:
          • Jean M. Tersak
    • Tennessee
      • Knoxville, Tennessee, United States, 37916
        • Recruiting
        • East Tennessee Childrens Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 865-541-8266
        • Principal Investigator:
          • Susan E. Spiller
    • Texas
      • Fort Worth, Texas, United States, 76104
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 713-798-1354
          • Email: burton@bcm.edu
        • Principal Investigator:
          • Maria M. Gramatges
      • San Antonio, Texas, United States, 78207
        • Recruiting
        • Children's Hospital of San Antonio
        • Contact:
        • Principal Investigator:
          • Julie Voeller
    • Virginia
      • Charlottesville, Virginia, United States, 22908
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • Seattle Children's Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 866-987-2000
        • Principal Investigator:
          • Sarah E. Leary
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin Carbone Cancer Center - University Hospital
        • Contact:
        • Principal Investigator:
          • Cathy A. Lee-Miller

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

7 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with pathologically confirmed classical Hodgkin Lymphoma (cHL) initially diagnosed when the patient was >= 2 and < 22 years of age

Description

Inclusion Criteria:

  • Patient must be >= 7 years of age at the time of enrollment (age to perform an MRI without sedation).
  • History of pathologically confirmed classical Hodgkin Lymphoma (cHL) initially diagnosed when the patient was >= 2 and < 22 years of age.

  • As part of frontline therapy for cHL, the patient must have received a cumulative doxorubicin equivalent anthracycline dose of ≥ 200 mg/m^2 as estimated in doxorubicin isotoxic equivalents dose conversion calculation.

    • Note: History of COG therapeutic trial participation is not required. Institutional records (e.g., clinic note, treatment summary, chemotherapy roadmap) can be used as reference documentation of receipt of anthracycline dose.
  • All systemic cancer treatment must have been completed ≥ 2 years prior to study enrollment.

  • Not known to have had a primary event (relapse/second malignancy/death).

    • Note: Subjects treated at another institution are eligible if they are now being followed at the current COG institution, if the study procedures can be performed and the data accessible by a COG institution where the study is open.
  • Patient must have access to cardiac MRI at the enrolling institution and must be able to complete cardiac MRI without sedation.

Exclusion Criteria:

  • Medical contraindication to undergoing a non-contrast cardiac MRI.
  • Patients with nodular lymphocyte-predominant HL.
  • Received cancer therapy in addition to that for primary Hodgkin Disease (e.g., for disease progression or recurrence, or subsequent malignant neoplasm).

  • History of CTCAE grade 3 or higher cardiovascular disease or condition known to exist prior to the patient's initial diagnosis of cHL.

    • Note: exceptions are made for congenital conditions considered fully resolved by surgery and chronic conditions such as hypertension or hypercholesterolemia that are managed with medical intervention.
  • History of an immunodeficiency that existed prior to cHL diagnosis, such as primary immunodeficiency syndromes, organ transplant recipients and conditions requiring systemic immunosuppressive agents.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Observational (blood samples, surveys, MRI, record review)
Patients undergo collection of blood samples, complete surveys, and undergo cardiac MRI on study. Patients also have their medical records reviewed and may have archived blood samples collected if available.
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Other: Survey Administration
Complete surveys
Other: Electronic Health Record Review
Undergo medical record abstraction
Procedure: Archive Sample Retrieval
Undergo collection of archived blood sample
Other Names:
  • ARCHIVE RETRIEVING

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Therapy-related clonal hematopoiesis (t-CH) with mutations associated with cardiovascular disease
Time Frame: Up to 1 year
Measured in the blood of eligible participants who were previously treated with anthracycline-containing therapy for pediatric classical Hodgkin lymphoma.
Up to 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Expansion of CH
Time Frame: 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.
Up to 1 year
Association between the presence of CVD and individual variables
Time Frame: 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).
Up to 1 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prevalence and nature of CVD, CH and CH with mutations associated with cardiovascular disease
Time Frame: 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). The VAFs and their exact 90% (Clopper-Pearson) confidence intervals are used to summarize the prevalence and nature of CVD, CH and CH with mutations associated with CVD for patients receiving mediastinal radiation.
Up to 1 year
Patient characteristics and treatments
Time Frame: Up to 1 year
The outcome here is the incidence of t-CH with mutation. The specific patient characteristic and treatments (age, sex, race, dexrazoxane usage etc.) will be used to predict the incidence of t-CH with mutation rate. Regression model will be constructed to evaluate the effect of these patient characteristics and treatments on the incidence of t-CH with mutation rate, which will be presented by p-values, coefficients and their confidence intervals.
Up to 1 year
Effect of therapy-related clonal hematopoiesis on cardiovascular disease
Time Frame: Up to 1 year
The outcome is the cardiovascular disease defined by cMRI. This aim is to evaluate the effect of other covariates such as patient characteristics (age, sex, race, etc.) and clinical conditions (radiation treatment with cardiac dosimetry, follow-up duration, etc.) on cardiovascular disease.
Up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Children's Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Robert J Hayashi, Children's Oncology Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 18, 2023

Primary Completion (Estimated)

October 1, 2028

Study Completion (Estimated)

October 1, 2028

Study Registration Dates

First Submitted

January 11, 2023

First Submitted That Met QC Criteria

January 20, 2023

First Posted (Actual)

January 30, 2023

Study Record Updates

Last Update Posted (Actual)

May 5, 2026

Last Update Submitted That Met QC Criteria

May 1, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ALTE21C1 (Other Identifier: CTEP)
  • UG1CA189955 (U.S. NIH Grant/Contract)
  • NCI-2022-09972 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • COG-ALTE21C1 (Other Identifier: DCP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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