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

Phase 4

Not yet recruiting

• Conditions: Immune Effector Cell Associated Neurotoxicity Syndrome
• Interventions: Biological: Biological tests; Diagnostic Test: MRI; Diagnostic Test: Neuropsychological tests

• Registration Number: NCT06706102
• Lead Sponsor: Centre Hospitalier Universitaire de Saint Etienne

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2024-10-14
• Study First Submitted QC: 2024-11-22
• Last Update Submitted: 2024-11-22
• Study First Posted: 2024-11-26
• Last Update Posted: 2024-11-26
• Study Start: 2025-01
• Primary Completion: 2027-09
• Study Completion: 2027-11

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

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.

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR T cell treatment	Biological tests	Major patients for whom CAR-T treatment is indicated.
CAR T cell treatment	MRI	Major patients for whom CAR-T treatment is indicated.
CAR T cell treatment	Neuropsychological tests	Major patients for whom CAR-T treatment is indicated.

Primary Outcome Measures

Name	Time	Method
Endothelial EVs quantification (EVs/mL)	Days -7, 0, 1, 2, 5, 8, 15, 30 and 60	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.
Endothelial EVs characterization (immunophenotyping)	Days -7, 0, 1, 2, 5, 8, 15, 30 and 60	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

CHU de Saint-Etienne; 🇫🇷 Saint-Étienne, France