Approaches to Identify Early Biomarkers and Pathogenesis of Anthracycline Cardiotoxicity

Study Overview
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Brief Summary
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Early microRNAs (miRs) and Cardiac Magnetic Resonance (CMR)-derived strain analysis and detection of genes contributing to Anthracycline-Induced Cardiotoxicity (AIC) sensitivity and resistance will identify pediatric cancer patients most and least likely to develop AIC.

Detailed Description
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Plan is to enroll 110 children and adults (≥9 years old) newly diagnosed at CCMC and Nationwide Children's Hospital (55 per institution) who will receive anthracyclines as part of their chemotherapy regimen. The duration of study participation will be approximately a year. Patients will have a total of four study visits: Baseline 1 week after patient's anthracycline cumulative dose hits between 60 and 100 mg/m2 After the patient has completed maximal therapy One year after completion of anthracycline treatments Study tasks for all four visits will be: Collection of clinical data Blood draw for micro RNA and Biomarkers Cardiac MRI Echocardiogram One time blood draw for genetics

Official Title
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Integrated Basis and Translational Approaches to Identify Early Biomarkers and Pathogenesis of Anthracycline Cardiotoxicity

Conditions
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Childhood Cancer

Intervention / Treatment
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* Other: Cardiac MRI
* Other: Echocardiogram
* Other: Blood Draw


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age (≥ 9years old) Newly diagnosed with a malignancy that will receive ACs as part of their chemotherapy. Parental/caregiver consent and subject assent to enrollment. Exclusion Criteria: Subject has contraindications to CMR.* Subject requiring sedation for CMR Subject too large to be safely accommodated by CMR Pregnancy tests are done routinely prior to chemotherapy, if test is positive the patient will be excluded Subject's serum creatinine above guidelines for adequate renal function. See table below: Age (years) Male Female 6-10 1.0 mg/dL 1.0 mg/dL 10-13 1.2 mg/dL 1.2 mg/dL 13-16 1.5 mg/dL 1.4 mg/dL >16 1.7 mg/dL 1.4 mg/dL

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Cardiac MRI|Patients will have a cardiac MRI at four time points during the study|
|Other: Echocardiogram|Patients will have an echocardiogram at four time points during the study|
|Other: Blood Draw|Patients will have blood drawn at four time points to analyze micro RNAs and Biomarkers before, during and after anthracycline treatment. Patients will also have one blood draw for future genetic sequencing.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CMR | 1. Increased myocardial T2 relaxation time in the myocardium compared to baseline as measured by T2 mapping technique | From Baseline to one year after anthracycline therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anthracycline induced cardiotoxicity