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| ID | Type | Description | Link |
|---|---|---|---|
| IDRCB 2023-A01957-38 | Other Identifier | ANSM |
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CAR-T cells (Chimeric Antigen Receptor) are a new immunotherapy, based on the genetic modification of autologous T lymphocytes. CAR-T cell therapy is not devoid of complications.
Among the most frequent complications are the risk of infection, cytokine release syndrome (CRS) and neurotoxicity. Nevertheless, some authors have reported serious acute cardiac events in a limited number of patients, often contemporaneous with CRS or sepsis, questioning the imputability of CAR-T cells in this heart disease.
This study aims to estimate the incidence of a possible early cardiotoxicity associated with CAR-T cells.
The main endpoint will be the change in cardiac function (LVEF: left ventricular ejection fraction) assessed by ultrasound between the pre CAR-T assessment and the early post CAR-T ultrasound (D3-D5).
CAR-T cells (Chimeric Antigen Receptor) represent a new form of immunotherapy, based on the genetic modification of autologous T lymphocytes collected after apheresis, allowing the recognition of a tumor antigen apart from the presentation by the major complex of histocompatibility (MHC). Treatment with CAR-T cells constitutes a major therapeutic advance in patients with refractory hematological malignancies.
Nevertheless, CAR-T cell therapy is often associated with severe complications leading them to the ICU in >25%.
Among the most frequent complications are the risk of infection cytokine release syndrome (CRS)and neurotoxicity. A recent study reported serious acute cardiac events in the days following the administration of CAR-T cells in 6.5% of patients (12/187). In this work, patients did not benefit from systematic early echocardiography, but only in the event of CRS grade ≥2 or symptoms, with a risk of underdiagnosis of asymptomatic forms. Since the vast majority of reported cases are contemporaneous with CRS or sepsis, the imputability of CAR-Ts in this heart disease is debated.
The Cardio CAR-T study aims to investigate a possible early cardiac toxicity of CAR-T cells, screened by transthoracic echocardiography at the patient's bedside, between D3 and D5 after injection of CAR-T cells (period at which the inflammatory complications of this treatment occur in the majority of cases) associated with the description of routine examinations (BNP, Troponin and ECG) and cytokine analyses.
This pilot descriptive study would answer 2 questions:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cardio CAR-T | Transthoracic bedside echocardiography |
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| Measure | Description | Time Frame |
|---|---|---|
| Estimation of the incidence of possible early CAR-T cells infusion-induced cardiotoxicity | Transthoracic bedside echocardiographic evaluation of the LVEF. | 5 days and 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Characterization of the putative CAR-T cells infusion-induced cardiotoxicity: incidence, phenotype, clinical, rhythmic and biological manifestations | Transthoracic bedside echocardiographic evaluation of the LVEF, EKG, biologicals (troponin, BNP). | 5 days and 3 months |
| Determination of its possible association with a cytokine release syndrome and the levels of inflammatory biomarkers from the analysis of the serum library of these patients |
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Inclusion Criteria:
Exclusion Criteria:
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Adult patients (>18 years old) receiving CAR-T cell therapy for hematological malignancies (acute lymphoblastic -B cell leukemia, lymphoma and multiple myeloma) hospitalized in hematology department or in intensive care unit.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jérémie JOFFRE, MD, PhD | Contact | +33 1 49 28 21 45 | Jeremie.joffre@aphp.fr | |
| Hafid AIT-OUFELLA, Professor | Contact | +33 1 49 28 21 45 | hafid.ait-oufella@aphp.fr |
| Name | Affiliation | Role |
|---|---|---|
| Jérémie JOFFRE | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Critical care medicine department | Recruiting | Paris | 75012 | France |
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| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D016393 | Lymphoma, B-Cell |
| D009101 | Multiple Myeloma |
| D009202 | Cardiomyopathies |
| D066126 | Cardiotoxicity |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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Plasma
Multiplex bioassays for immune-inflammatory biomarkers. |
| 5 days and 3 months |
| D007945 |
| Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D054219 | Neoplasms, Plasma Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D006331 | Heart Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D011832 | Radiation Injuries |
| D014947 | Wounds and Injuries |