CAR T Cell Therapy Related Cardiovascular Outcomes

Study Overview
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Brief Summary
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This will be a cohort study of all patients receiving Cluster of Differentiation 19 (CD19)-specific CAR T cell therapy for relapsed/refractory B cell haematological malignancies. Patients will receive cardiac assessment and have serum cardiac biomarkers, ECG, transthoracic echocardiogram and cardiac magnetic resonance imaging performed at baseline prior to CAR T cell therapy, 7 days post CAR T cell infusion, and 3 months post CAR T cell infusion. Abnormalities in these cardiac investigations will be used to demonstrate cardiac injury and identify which patients are most at risk of developing cardiac injury related to CAR T cell therapy.

Detailed Description
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CD19-specific chimeric antigen receptor (CAR) T cells are a novel therapy for relapsing or refractory blood cancers, which have delivered a significant improvement in the rates of complete and partial remission. However, they are associated with toxicities, with some of early evidence suggestive of cardiovascular involvement. Despite this, the full extent of cardiovascular toxicity is poorly understood. This research study seeks to understand the cardiac safety of CAR T cells in patients who receive this therapy as part of standard care for relapsed/refractory B-cell blood cancer. They will be assessed for cardiovascular risk factors via history, blood biomarkers, and cardiac imaging tests. These parameters will be repeated at 7 days following administration of the CAR T cells or if there are signs of cardiovascular deterioration, and again at 3 months follow up. The aim is to predict the cohort most at risk of cardiovascular toxicity, and demonstrate evidence of cardiac injury on the cardiac imaging scans.

Official Title
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Chimeric Antigen Receptor (CAR) Cell Therapy Related Cardiovascular Outcomes

Conditions
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Cardiovascular Diseases, B-cell Acute Lymphoblastic Leukemia, B-cell Lymphoma Refractory, B-cell Lymphoma Recurrent, Primary Mediastinal Large B-cell Lymphoma (PMBCL), Diffuse Large B Cell Lymphoma, Cardiotoxicity, Cardiovascular Complication

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with capacity, (aged 16 and older) Undergoing CAR T cells for treatment for relapsing or refractory haematological malignancies Exclusion Criteria: Patients under 16 years

Ages Eligible for Study
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Minimum Age: 16 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detected abnormalities - Composite | The primary outcome is a composite of detected abnormalities on biomarkers, transthoracic echocardiogram (TTE), or Cardiac magnetic resonance (CMR) following CAR T cell infusion. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detected abnormalities - Individual | The secondary outcome measures includes a composite of detected abnormalities of factors on cardiac biomarkers (troponin and N-terminal pro B-type natriuretic peptide) , electrocardiogram (ECG) changes and acute heart failure. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardio-oncology, CAR T cell therapy, Cardiotoxicity