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

Multiple Myeloma Clinical Trial

— Cardio CAR-T  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06350994
• Other study ID #: APHP230625
• Secondary ID: IDRCB 2023-A0195
• Status: Not yet recruiting
• Start date: September 2024
• Est. completion date: January 2027

Study information

• Verified date: April 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Jérémie JOFFRE, MD, PhD
• Phone: +33 1 49 28 21 45
• Email: Jeremie.joffre[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: January 2027
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Hematologic Malignancy
• Hematologic Neoplasms
• Lymphoma, B-Cell
• Multiple Myeloma
• Neoplasms
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Locations

Country	Name	City	State
France	Critical care medicine department	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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