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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2022-09972 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| ALTE21C1 | Other Identifier | Children's Oncology Group | |
| COG-ALTE21C1 | Other Identifier | DCP | |
| ALTE21C1 | Other Identifier | CTEP | |
| UG1CA189955 | U.S. NIH Grant/Contract | View source |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Archive Sample Retrieval | Procedure | Undergo collection of archived blood sample |
|
| Measure | Description | Time Frame |
|---|---|---|
| Therapy-related clonal hematopoiesis (t-CH) with mutations associated with cardiovascular disease | Measured in the blood of eligible participants who were previously treated with anthracycline-containing therapy for pediatric classical Hodgkin lymphoma. | Up to 1 year |
| 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. |
| 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. |
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.
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).
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.
History of an immunodeficiency that existed prior to cHL diagnosis, such as primary immunodeficiency syndromes, organ transplant recipients and conditions requiring systemic immunosuppressive agents.
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Patients with pathologically confirmed classical Hodgkin Lymphoma (cHL) initially diagnosed when the patient was >= 2 and < 22 years of age
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| Name | Affiliation | Role |
|---|---|---|
| Robert J Hayashi | Children's Oncology Group | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| USA Health Strada Patient Care Center | Recruiting | Mobile | Alabama | 36604 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37505794 | Derived | 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. |
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Blood
| Biospecimen Collection | Procedure | Undergo blood sample collection |
|
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| Electronic Health Record Review | Other | Undergo medical record abstraction |
|
| Magnetic Resonance Imaging | Procedure | Undergo MRI |
|
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| Survey Administration | Other | Complete surveys |
|
| 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 |
| 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, 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 | 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 |
| Phoenix Childrens Hospital | Recruiting | Phoenix | Arizona | 85016 | United States |
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| City of Hope Comprehensive Cancer Center | Recruiting | Duarte | California | 91010 | United States |
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| Connecticut Children's Medical Center | Recruiting | Hartford | Connecticut | 06106 | United States |
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| Yale University | Recruiting | New Haven | Connecticut | 06520 | United States |
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| Alfred I duPont Hospital for Children | Recruiting | Wilmington | Delaware | 19803 | United States |
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| Golisano Children's Hospital of Southwest Florida | Recruiting | Fort Myers | Florida | 33908 | United States |
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| Arnold Palmer Hospital for Children | Recruiting | Orlando | Florida | 32806 | United States |
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| Saint Joseph's Hospital/Children's Hospital-Tampa | Recruiting | Tampa | Florida | 33607 | United States |
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| Children's Healthcare of Atlanta - Arthur M Blank Hospital | Recruiting | Atlanta | Georgia | 30329 | United States |
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| Southern Illinois University School of Medicine | Recruiting | Springfield | Illinois | 62702 | United States |
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| University of Maryland/Greenebaum Cancer Center | Recruiting | Baltimore | Maryland | 21201 | United States |
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| C S Mott Children's Hospital | Recruiting | Ann Arbor | Michigan | 48109 | United States |
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| Children's Hospitals and Clinics of Minnesota - Minneapolis | Recruiting | Minneapolis | Minnesota | 55404 | United States |
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| Washington University School of Medicine | Recruiting | St Louis | Missouri | 63110 | United States |
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| Hackensack University Medical Center | Recruiting | Hackensack | New Jersey | 07601 | United States |
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| Albany Medical Center | Recruiting | Albany | New York | 12208 | United States |
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| Roswell Park Cancer Institute | Recruiting | Buffalo | New York | 14263 | United States |
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| Wake Forest University Health Sciences | Recruiting | Winston-Salem | North Carolina | 27157 | United States |
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| Cincinnati Children's Hospital Medical Center | Recruiting | Cincinnati | Ohio | 45229 | United States |
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| Nationwide Children's Hospital | Recruiting | Columbus | Ohio | 43205 | United States |
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| Oregon Health and Science University | Recruiting | Portland | Oregon | 97239 | United States |
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| Children's Hospital of Philadelphia | Recruiting | Philadelphia | Pennsylvania | 19104 | United States |
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| Children's Hospital of Pittsburgh of UPMC | Recruiting | Pittsburgh | Pennsylvania | 15224 | United States |
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| East Tennessee Childrens Hospital | Recruiting | Knoxville | Tennessee | 37916 | United States |
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| Cook Children's Medical Center | Recruiting | Fort Worth | Texas | 76104 | United States |
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| Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center | Recruiting | Houston | Texas | 77030 | United States |
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| Children's Hospital of San Antonio | Recruiting | San Antonio | Texas | 78207 | United States |
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| University of Virginia Cancer Center | Recruiting | Charlottesville | Virginia | 22908 | United States |
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| Seattle Children's Hospital | Recruiting | Seattle | Washington | 98105 | United States |
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| University of Wisconsin Carbone Cancer Center - University Hospital | Recruiting | Madison | Wisconsin | 53792 | United States |
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| Hospital for Sick Children | Suspended | Toronto | Ontario | M5G 1X8 | Canada |
| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D009682 | Magnetic Resonance Spectroscopy |
| ID | Term |
|---|---|
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D008919 | Investigative Techniques |
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
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