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

Official title

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

Overview

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.

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.

Interventions

• Procedure Archive Sample Retrieval
  Undergo collection of archived blood sample
• Procedure Biospecimen Collection
  Undergo blood sample collection
• Other Electronic Health Record Review
  Undergo medical record abstraction
• Procedure Magnetic Resonance Imaging
  Undergo MRI
• Other Survey Administration
  Complete surveys

Primary outcome measures

• Therapy-related clonal hematopoiesis (t-CH) with mutations associated with cardiovascular disease [Time frame: Up to 1 year]

Secondary outcome measures (2)

• Expansion of CH [Time frame: Up to 1 year]
• Association between the presence of CVD and individual variables [Time frame: Up to 1 year]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Other

Study locations

United States · 35 centers

• USA Health Strada Patient Care Center — Mobile
• Phoenix Childrens Hospital — Phoenix
• City of Hope Comprehensive Cancer Center — Duarte
• Valley Children's Hospital — Madera
• Connecticut Children's Medical Center — Hartford
• Yale University — New Haven
• Alfred I duPont Hospital for Children — Wilmington
• Golisano Children's Hospital of Southwest Florida — Fort Myers
• … and 27 more centers

Canada · 1 center

• Hospital for Sick Children — Toronto

Publications

• Castellino SM, Giulino-Roth L, Harker-Murray P, Kahn JM, Forlenza C, Cho S, Hoppe B, Parsons SK, Kelly KM; COG Hodgkin Lymphoma Committee. Children's Oncology Group's 2023 blueprint for research: Hodgkin lymphoma. Pediatr Blood Cancer. 2023 Sep;70 Suppl 6(Suppl 6):e30580. doi: 10.1002/pbc.30580. Epub 2023 Jul 28. PMID 37505794

Identifiers

NCT: NCT05705531 · ALTE21C1 · NCI-2022-09972 · ALTE21C1 · COG-ALTE21C1 · ALTE21C1 · UG1CA189955

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗