Early Assessment of Cardiac Function After Treatment With CAR-T Cells (Cardio CAR-T)

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).

Study Overview

• Status: Recruiting
• Conditions: Lymphoma, B-Cell; Multiple Myeloma; Acute Lymphoblastic Leukemia; Hematologic Malignancy; Car T- Cell

Detailed Description

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:

• What are the incidence and characteristics of acute cardiac toxicity (clinical and subclinical) of CAR-T cells and their association with CRS?
• Is there a link between cardiac toxicity and the intensity of the cytokine inflammatory response? This makes it possible to provide new pathophysiological elements on the existence of a heart disease directly caused by the inflammatory storm, applicable to other areas such as septic shock, ischemia-reperfusion or major surgery.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Jérémie JOFFRE, MD, PhD; Phone Number: +33 1 49 28 21 45; Email: Jeremie.joffre@aphp.fr
• Study Contact Backup: Name: Hafid AIT-OUFELLA, Professor; Phone Number: +33 1 49 28 21 45; Email: hafid.ait-oufella@aphp.fr

Study Locations

• France
  • Paris, France, 75012
    • Recruiting
    • Critical care medicine department
    • Contact: Jérémie JOFFRE, MD, PhD; Phone Number: +33 1 49 28 21 45; Email: Jeremie.joffre@aphp.fr
    • Contact: Hafid AIT-OUFELLA, Professor; Phone Number: +33 1 49 28 21 45; Email: hafid.ait-oufella@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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.

Description

Inclusion Criteria:

• CAR-T cells infusion received within 3 to 5 days before the echocardiography
• Pre-therapeutic cardiac assessment (in accordance with the recommendations and standard care protocol in force in the hematology department of Saint-Antoine Hospital): Echocardiography and EKG before conditioning and infusion of CAR -T cells,
• Not opposed to participating in research.
• Patient affiliated to a social security system or beneficiary of the "state medical insurance help" (namely aide médicale d'état).

Exclusion Criteria:

• Opposition or consent withdrawal

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Cardio CAR-T; Transthoracic bedside echocardiography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	Multiplex bioassays for immune-inflammatory biomarkers.	5 days and 3 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Jérémie JOFFRE, Assistance Publique - Hopitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: February 21, 2024
• First Submitted That Met QC Criteria: April 3, 2024
• First Posted (Actual): April 8, 2024

Study Record Updates

• Last Update Posted (Estimated): September 2, 2025
• Last Update Submitted That Met QC Criteria: August 29, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Cardiomyopathy; Cardiotoxicity; CAR-T cells; Pharmacovigilance; Hematological malignancies
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Neoplasms by Site; Neoplasms; Heart Diseases; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Chemically-Induced Disorders; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Lymphoma, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Multiple Myeloma; Cardiomyopathies; Cardiotoxicity
• Other Study ID Numbers: APHP230625; IDRCB 2023-A01957-38 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No