Temporal Characterization of Extracellular Vesicles During Cellular Therapy Using CAR-T Cells and During the Occurrence of Immune Effector Cell-Associated Neurotoxicity Syndrome (VESICANS)

Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS) is a common and serious neurological complication associated with the use of CAR-T cells. The mechanisms involved are still poorly understood but studies suggest that inflammation during treatment leads to an increase in the permeability of the barrier between the brain and the blood vessels and the emission of extracellular vesicles (EVs) circulating between the brain and the blood vessels. EVs are biological particles that play an important role in cellular communication and the modulation of several physiological processes. The VESICANS study aims to characterize the EVs released before and during CAR-T cells treatment and upon the occurrence of ICANS, using flow cytometry, electron microscopy, Nanoparticle Tracking Analysis associated with MRI assessment of the barrier between the brain and blood. This study will ultimately contribute to facilitating the prevention and treatment of this toxicity which affects the prognosis of patients.

Study Overview

• Status: Recruiting
• Conditions: Immune Effector Cell Associated Neurotoxicity Syndrome
• Intervention / Treatment: Diagnostic test: MRI; Biological: Biological tests; Diagnostic test: Neuropsychological tests

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Emilie CHALAYER, MD; Phone Number: +33 (0)4 77 82 28 14; Email: emilie.chalayer@chu-st-etienne.fr
• Study Contact Backup: Name: Hélène RAINGARD; Phone Number: +33 (0)4 77 82 97 03; Email: helene.raingard@chu-st-etienne.fr

Study Locations

• France
  • Saint-Étienne, France, 42055
    • Recruiting
    • CHU de Saint-Etienne
    • Sub-Investigator: Ludovic FOUILLET, MD
    • Sub-Investigator: Emmanuelle TAVERNIER, MD
    • Contact: Emilie CHALAYER, MD; Phone Number: 33 (0)4 77 82 28 14; Email: emilie.chalayer@chu-st-etienne.fr
    • Sub-Investigator: Jérôme CORNILLON, MD
    • Sub-Investigator: Manon SAPET, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient aged over 18,
• Patient for whom CAR-T treatment is indicated,
• Patient affiliated to a social security system
• Patient who give his consent to participate in the study.

Exclusion Criteria:

• Pregnant or breastfeeding woman,
• Patient unable to understand informed consent,
• Patient under legal protection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAR T cell treatment; Major patients for whom CAR-T treatment is indicated.	Diagnostic test: MRI; MRI; Biological: Biological tests; Biological tests : cell quantification et characterization; Diagnostic test: Neuropsychological tests; Neuropsychological tests

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelial EVs quantification (EVs/mL)	Quantification by Nano Tracking Analysis of endothelial EVs as a function of time before and after treatment with CAR-T cells according to ICANS grade.	Days -7, 0, 1, 2, 5, 8, 15, 30 and 60
Endothelial EVs characterization (immunophenotyping)	Characterization by Nano Tracking Analysis (immunophenotyping by size) of endothelial EVs as a function of time before and after treatment with CAR-T cells according to ICANS grade.	Days -7, 0, 1, 2, 5, 8, 15, 30 and 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Other EV subtypes quantification (EV subtype/mL)	Other EV subtypes quantification of as a function of time before and after treatment with CAR-T cells according to ICANS grade.	Days -7, 0, 1, 2, 5, 8, 15, 30 and 60
Other EV subtypes characterization (immunophenotyping)	Other EV subtypes characterization of as a function of time before and after treatment with CAR-T cells according to ICANS grade.	Days -7, 0, 1, 2, 5, 8, 15, 30 and 60
EVS quantification according to the presence of an ICANS versus no ICANS (EV/mL)	EVS quantification according to the presence of an ICANS versus no ICANS	Days -7, 0, 1, 2, 5, 8, 15, 30 and 60
EVs characterization according to the presence of an ICANS versus no ICANS (immunophenotyping)	EVS characterization of EVs according to the presence of an ICANS versus no ICANS	Days -7, 0, 1, 2, 5, 8, 15, 30 and 60
EVs quantification according to levels of cytokines (EVs/mL)	EVs quantification according to levels of cytokines	Days -7, 0, 1, 2, 5, 8, 15, 30 and 60
EVs characterization according to levels of cytokines	EVs characterization according to levels of cytokines	Days -7, 0, 1, 2, 5, 8, 15, 30 and 60
EVs quantification in cerebrospinal fluid (EVs/mL)	EVs quantification after treatment with CAR-T cells in cerebrospinal fluid (CSF) if available.	Days -7, 0, 1, 2, 5, 8, 15, 30 and 60
EVs characterization in cerebrosinalfluid.	EVs characterization of EVs after treatment with CAR-T cells in cerebrospinal fluid (CSF) if available.	Days -7, 0, 1, 2, 5, 8, 15, 30 and 60
Association of EVs subpopulations in clinical neurological damage and sleep apnea syndrome.	Characterization of the association of subpopulations of EVs according to clinical neurological damage and sleep apnea syndrome.	Days -7, 0, 1, 2, 5, 8, 15, 30 and 60
Association of EVs subpopulations in neuropsychological test and RMI.	Characterization of the association of subpopulations of EVs according to neuropsychological test and RMI.	Days -7, 0, 1, 2, 5, 8, 15, 30 and 60
Cerabral involvement on RMI	Diffusion tensor imaging and resting state default mode network	Days -7, 0, 1, 2, 5, 8, 15, 30 and 60

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Investigators: Principal Investigator: Emilie CHALAYER, MD, CHU Saint-Etienne

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: October 14, 2024
• First Submitted That Met QC Criteria: November 22, 2024
• First Posted (Actual): November 26, 2024

Study Record Updates

• Last Update Posted (Actual): July 9, 2025
• Last Update Submitted That Met QC Criteria: July 4, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: CAR-T Cell; ICANS; EVs
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Disease; Chemically-Induced Disorders; Poisoning; Syndrome; Neurotoxicity Syndromes
• Other Study ID Numbers: 24CH009; 2024-515328-35-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No