Identification and Evaluation of Patients at Risk of Developing Cardiotoxicity After Receiving Chemotherapy for Breast Cancer, Lymphoma or Leukemia

Study Overview
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Brief Summary
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This is an observational study of the occurrence of cardiac toxicity in patients with breast cancer,lymphoma or leukemia receiving chemotherapy including an anthracycline. Patients will be identified at the oncology clinic and will be included in the study if all eligible criteria are met. The study will involve retrospective and prospective evaluations. Safety will be assessed through reporting of serious adverse events (SAEs) related to study procedures.

Detailed Description
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The aim of this study is to identify and evaluate cardiotoxicity in patients with diagnosis of breast cancer, lymphoma or leukemia scheduled to receive anthracycline-based chemotherapy (Cohort A: prospective evaluation); and patients undergoing or having received within the last 5 years anthracycline-based chemotherapy (Cohort B: retrospective and prospective evaluations). Part A and B will be conducted in parallel. This study also has the objectif of identifying biomarkers of cardiotoxicity including inflammatory response proteins and clonal hematopoiesis.

Official Title
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Identification and Evaluation of Patients at Risk of Developing Cardiotoxicity After Receiving Chemotherapy for Breast Cancer, Lymphoma or Leukemia

Conditions
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Breast Cancer, Lymphoma, Leukemia

Intervention / Treatment
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* Diagnostic Test: Cardiac Imaging
* Other: Data Collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older at time of CT initiation Signed informed consent Patients with diagnosis of breast cancer,lymphoma or leukemia (including autografted subjects) Planned, ongoing or completed (within last 5 years) chemotherapy with anthracycline Left ventricular ejection fraction (LVEF) ≥50% pre-chemotherapy The participant is willing to undergo CMR scans and all other required study procedures Exclusion Criteria: Known cardiomyopathy and/or LVEF <50% Known heart failure History of myocardial infarction (MI) Clinically significant cardiac valvular disease Clinically significant pericardial effusion Allografted subjects Contraindications to CMR testing (Cohort A & prospective evaluation for Cohort B): Pacemakers, other metallic implants or severe claustrophobia Weight > 135 kg Patients with a history of previous allergic reaction to gadolinium Patients with history of seizure Renal insufficiency (eGFR of < 45ml/min/1.73m2 using the MDRD equation) Pregnant or breastfeeding women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort A<br>Prospective | Diagnostic Test: Cardiac Imaging<br>* Cardiac Imaging: echography, ECG, MRI Blood tests: Lipid profile, hs-CRP, metabolic markers, HDL functionality, pharmacogenetic testing (optional), hematocrit, pregnancy test<br>* Other names: Blood tests;|
| Cohort B<br>Retrospective/Prospective | Diagnostic Test: Cardiac Imaging<br>* Cardiac Imaging: echography, ECG, MRI Blood tests: Lipid profile, hs-CRP, metabolic markers, HDL functionality, pharmacogenetic testing (optional), hematocrit, pregnancy test<br>* Other names: Blood tests;Other: Data Collection<br>* Collection of retrospective data<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myocardial extracellular volume (ECV) | Cohort A | Change from baseline to 3, 6, 12,and 24 months | 
| Myocardial extracellular volume (ECV) | Cohort B | Change from baseline to prior study entry, 12 and 24 months post study entry. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular (LV) systolic function (global and regional) | Cohort A | Change from baseline to 3, 6, 12,and 24 months. | 
| Biomarker of myocardial injury (high-sensitivity troponin (hs-cTn)) | Cohort A | Change from baseline to 3, 6, 12,and 24 months. | 
| Biomarker of elevated LV fitting pressure (N-Terminal-pro-hormone B-type Natriuretic Peptide (NT-proBNP)) | Cohort A | Change from baseline to 3, 6, 12,and 24 months. | 
| Biomarker of inflammation (high-sensitivity C-reactive protein (hs-CRP)) | Cohort A | Change from baseline to 3, 6, 12,and 24 months. | 
| Clonal hematopoiesis associated gene mutations. | Cohort A | Change from baseline to 24 months.. | 
| Telomere length measurement | Cohort A | Change from baseline to 24 months.. | 
| Left ventricular (LV) systolic function (global and regional) | Cohort B | Change from study entry to 12 and 24 months. | 
| Biomarker of myocardial injury (high-sensitivity troponin (hs-cTn)) | Cohort B | Change from study entry to 12 and 24 months. | 
| Biomarker of elevated LV fitting pressure (N-Terminal-pro-hormone B-type Natriuretic Peptide (NT-proBNP)) | Cohort B | Change from study entry to 12 and 24 months. | 
| Biomarker of inflammation (high-sensitivity C-reactive protein (hs-CRP)) | Cohort B | Change from study entry to 12 and 24 months. | 
| Clonal hematopoiesis associated gene mutations. | Cohort B | Change from baseline to 24 months.. | 
| Telomere length measurement | Cohort B | Change from baseline to 24 months.. |