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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hodgkin Lymphoma; Cardiovascular Disorder; Clonal Hematopoiesis
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Other: Survey Administration; Procedure: Biospecimen Collection; Other: Electronic Health Record Review

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 Type: Observational
• Enrollment (Estimated): 230

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33607
      • Recruiting
      • Saint Joseph's Hospital/Children's Hospital-Tampa
      • Contact: Site Public Contact; Phone Number: 813-357-0849; Email: jennifer.manns@baycare.org
      • Principal Investigator: Don E. Eslin
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Contact: Site Public Contact; Phone Number: 800-600-3606; Email: info@siteman.wustl.edu
      • Principal Investigator: Robert J. Hayashi
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Hackensack University Medical Center
      • Contact: Site Public Contact; Phone Number: 201-996-2879
      • Principal Investigator: Katharine R. Lange
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Cancer Institute
      • Contact: Site Public Contact; Phone Number: 800-767-9355; Email: askroswell@roswellpark.org
      • Principal Investigator: Kara M. Kelly
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Recruiting
      • Nationwide Children's Hospital
      • Contact: Site Public Contact; Phone Number: 614-722-6039; Email: Melinda.Triplet@nationwidechildrens.org
      • Principal Investigator: Mark A. Ranalli
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University
      • Contact: Site Public Contact; Phone Number: 503-494-1080; Email: trials@ohsu.edu
      • Principal Investigator: Susan J. Lindemulder
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Principal Investigator: Jill P. Ginsberg
      • Contact: Site Public Contact; Phone Number: 267-425-5544; Email: CancerTrials@email.chop.edu
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • Children's Hospital of Pittsburgh of UPMC
      • Contact: Site Public Contact; Phone Number: 412-692-8570; Email: jean.tersak@chp.edu
      • Principal Investigator: Jean M. Tersak
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • Cook Children's Medical Center
      • Contact: Site Public Contact; Phone Number: 682-885-2103; Email: CookChildrensResearch@cookchildrens.org
      • Principal Investigator: Donald T. Beam
    • San Antonio, Texas, United States, 78207
      • Recruiting
      • Children's Hospital of San Antonio
      • Contact: Site Public Contact; Phone Number: 210-704-2894; Email: bridget.medina@christushealth.org
      • Principal Investigator: Timothy C. Griffin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years and older (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Prior to enrollment on this study, patients must have been enrolled on AHOD1331.

Description

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 Plan

How is the study designed?

Design Details

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

Number of groups / cohorts

1

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.

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 (procedure); Other: Survey Administration; Complete surveys; Procedure: Biospecimen Collection; Undergo blood specimen collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Other: Electronic Health Record Review; Undergo medical record abstraction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective signs of CVD	Left Ventricular Ejection Fraction (LVEF), < 55%	Up to 1 year
Objective signs of CVD	Global Longitudinal Strain (GLS) less negative than -18%	Up to 1 year
Objective signs of CVD	Left Ventricular End Diastolic Volume indexed to body surface are (LVEDVi) > 85 mL:/meter^2.	Up to 1 year
Proportion of therapy-related clonal hematopoiesis (t-CH) for patients with cardiovascular disease (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.	Up to 1 year
Proportion of t-CH with mutations for patients with CVD after Hodgkin Lymphoma therapy	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.	Up to 1 year
Proportion of t-CH 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.	Up to 1 year
Proportion of t-CH with mutations 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.	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expansion of CH	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	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	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	The outcome here is the incidence of t-CH with mutation. The specific patient characteristic and treatments (age, gender, 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	The outcome is the cardiovascular disease defined by cMRI. This aim is to evaluate the effect of other covariates such as patient characteristics (age, gender, race, etc.) and clinical conditions (radiation treatment with cardiac dosimetry, follow-up duration, etc.) on cardiovascular disease.	Up to 1 year

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Robert J Hayashi, Children's Oncology Group

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 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 (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Cardiovascular Diseases; Hodgkin Disease
• 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