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

Hodgkin Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05705531
• Other study ID #: ALTE21C1
• Secondary ID: NCI-2022-09972AL
• Status: Recruiting
• Start date: August 18, 2023
• Est. completion date: October 1, 2028

Study information

• Verified date: May 2024
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 230
• Est. completion date: October 1, 2028
• Est. primary completion date: October 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Cardiovascular Disorder
• Clonal Hematopoiesis
• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma

Intervention

Procedure:
• Biospecimen Collection
Undergo blood specimen collection

Other:
• Electronic Health Record Review
Undergo medical record abstraction

Procedure:
• Magnetic Resonance Imaging
Undergo MRI

Other:
• Survey Administration
Complete surveys

Locations

Country	Name	City	State
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Children's Hospital of San Antonio	San Antonio	Texas
United States	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Objective signs of CVD	Left Ventricular Ejection Fraction (LVEF), < 55%	Up to 1 year
Primary	Objective signs of CVD	Global Longitudinal Strain (GLS) less negative than -18%	Up to 1 year
Primary	Objective signs of CVD	Left Ventricular End Diastolic Volume indexed to body surface are (LVEDVi) > 85 mL:/meter^2.	Up to 1 year
Secondary	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
Secondary	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