Assessment of Clonal Hematopoiesis and Its Relationship to Cardiovascular Disease in Hodgkin Lymphoma Survivors
Study Details
Study Description
Brief Summary
This study will capitalize on technologies that can detect the presence of t-CH at very low levels to determine whether such clones emerge from therapy, expand over time and whose presence correlate with early signs of CVD as detected by cardiac MRI.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
PRIMARY OBJECTIVES:
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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.
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To assess participants of AHOD1331 with t-CH for the presence or absence of objective signs of CVD using cardiac MRI.
SECONDARY OBJECTIVES:
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To assess whether participants in AHOD1331 with t-CH expand this population over time and possess objective findings of CVD.
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To assess whether patients both with and without objective findings of CVD using cardiac MRI possess clinical risk factors for CVD.
EXPLORATORY OBJECTIVES:
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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.
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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.
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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:
Participants from the recent COG trial, (AHOD1331) will be recruited for this study. Both freshly collected blood specimens and archived samples will be assessed for the presence of t-CH and a cardiac MRI will be obtained to assess the presence of CVD as it provides the most sensitive means of detecting early cardiac injury from anthracycline chemotherapy.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Observational (Specimen Collection, Clinical Measures, Patient Surveys) Archived blood samples will be obtained prior to therapy initiation and at the end of therapy. Subsequent samples will be collected in conjunction with cMRI imaging. Blood samples will be obtained at two study time points, separated by a year. Additional data from patient surveys and basic laboratory tests will be completed. |
Other: Patient Self Reporting
Completion of Healthy Cardiac Lifestyle Survey
Procedure: Clinical Evaluations
Fasting laboratory tests (cholesterol, triglycerides, HDL-C and blood glucose) will be completed locally as per routine monitoring for cardiac health
Procedure: Study Blood Sampling
Collection of a peripheral blood sample
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Outcome Measures
Primary Outcome Measures
- The proportions of t-CH and t-CH with mutation for patients with or without CVD after Hodgkin Lymphoma therapy [Up to 4 years]
The proportions will be compared with one-sided Z-Test with normal approximation and significance level 0.05.
Secondary Outcome Measures
- Assess whether participants in AHOD1331 with t-CH expand this population over time and possess objective findings of CVD. [Up to 4 years]
The time varying trend in the association between the expansion of CH over time and the presence/worsening of CVD signs. Graphic analysis will be used 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.
- The number of patients with and without objective findings of CVD using cardiac MRI possess clinical risk factors for CVD. [Up to 4 years]
The number of patients with the presence of CVD and the individual variables constituting the clinical profile. Either parametric (e.g., independent t-test, χ2-test, Pearson correlation coefficients) or non-parametric (e.g., Wilcoxon rank sum tests, Spearman's rank correlation coefficients) methods will be applied.
Other Outcome Measures
- 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 [Up to 4 years]
The sample proportions 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.
- Assess whether specific patient characteristics and treatment correlate with a higher incidence of t-CH with mutations associated with CVD [Up to 4 years]
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. Comparisons will be conducted to compare the patient characteristic and treatments between the with and without mutation group. 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.
- 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 [Up to 4 years]
The effects of t-CH on CVD will be evaluated by considering other covariates such as patient characteristics (age, gender, race, etc.) and clinical conditions (RT treatment with cardiac dosimetry, follow-up duration, etc.). A multivariable model will be constructed with CVD as the endpoint and t-CH as the explanatory variable together with other covariates such as patient characteristics and clinical conditions.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Enrolled and completed therapy on AHOD1331.
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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 COG institution.
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Patient must have access to cardiac MRI at institution where receiving follow-up care and must be able to complete cardiac MRI without sedation.
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All patients and/or their parents or legal guardians must sign a written informed consent.
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All institutional, FDA, and NCI requirements for human studies must be met.
Exclusion Criteria:
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Medical contraindication to undergoing a cardiac MRI.
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Removed from AHOD1331 therapy prior to completing the AHOD1331 protocol specified treatment plan.
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Received cancer therapy in addition to that of AHOD1331 (e.g., for disease progression or recurrence, or subsequent malignant neoplasm).
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History of cardiovascular disease prior to enrollment on AHOD1331.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Children's Oncology Group
- National Cancer Institute (NCI)
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ALTE21C1