Magnetic Resonance Imaging in Immune Effector Cell-Associated Neurotoxicity Syndrome

NCT05510596 | Completed DMC

• 1 other identifier: RECHMPL20_0424
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The treatment of large-cell B-cell lymphomas refractory to more than 2 lines of therapy has recently been revolutionized by the use of immunotherapies consisting of autologous genetically modified cells or CAR-T CELLS (chimeric antigen receptor-T cells), which very significantly increase progression-free survival and overall survival. Nevertheless, this therapy is frequently associated with cytokine release syndrome and in approximately 20% to 60% of patients with neurological complications that can sometimes be dramatic and are associated with a significant mortality rate. The mechanisms behind this neurotoxicity are unclear. Despite the frequent occurrence of neurological toxicity characterized in particular by headache, tremor, and encephalopathy that is most often transient, brain imaging by CT or, preferably, MRI are most often normal. The rare abnormalities that have been identified suggest the presence of cytotoxic edema associated with the existence of transient modifications of the blood-brain barrier. To date, the management of neurotoxicity associated with CAR-T CELLS remains empirical. It combines early management of cytokine release syndrome (by administration of anti-IL6) and treatment with corticosteroids, the objective of which would be to control neurotoxicity more specifically. A better understanding of the pathophysiological mechanisms associated with this neurotoxicity appears essential today in order to be able to propose adapted prevention and treatment methods. Main objectives are to compare tissue permeability by quantitative MRI measurement of Ktrans to the theoretical peak of neurotoxicity between patients with CAR-T Cell-induced neurotoxicity and those without neurotoxicity and to Study, by MRI, the evolution of tissue microcirculatory parameters (from D-3 to D7) between groups of patients with or without the occurrence of neurotoxicity associated with CAR-T CELL treatment. For this purpose, 25 subjects will be included (the investigators hypothesize 40% with treatment-induced neurological impairment).

Conditions

Lymphoma, B-Cell; Neurotoxicity

Keywords

Neurotoxicity; CAR-T CELLS; Immune cells associated neurotoxicity syndrome; Cytokine release syndrome

Outcome Measures

Primary Outcomes (1)

• Study of tissue permeability evolution

  Quantitative measurement of KTRANS (rate of contrast agent transfer from plasma to the extravascular extracellular space, reflecting capillary permeability). (Time in second)

  10 days

Secondary Outcomes (16)

• Qualitative analysis of tissue signals

  10 days

• Qualitative analysis

  10 days

• Qualitative analysis

  10 days

• Semi-quantitative analysis of parameters associated with permeability

  10 days

• Semi-quantitative analysis of parameters associated with permeability

  10 days

Study Arms (1)

Patients with CAR-T Cell treatment

OTHER

Single arm All patient will undergo an MRI with contrast injection, a blood withdrawal and a neurological consultation with neuropsychological tests

Other: Magnetic Resonance Imaging with contrast injection; Other: Blood withdrawal; Other: Neuropsychological tests

Interventions

Magnetic Resonance Imaging with contrast injection OTHER

Magnetic Resonance Imaging with contrast injection

Patients with CAR-T Cell treatment

Blood withdrawal OTHER

Blood withdrawal : serum, plasma, cytokine assay

Patients with CAR-T Cell treatment

Neuropsychological tests OTHER

Neuropsychological tests

Patients with CAR-T Cell treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject aged from 18 years old
• Subject able to understand the nature, purpose and methodology of the study
• Subject with diffuse large B-cell lymphoma to be treated with axicabtagene ciloleucel, tisagenlecleucel or brexucabtagene autoleucel for their lymphoma.

You may not qualify if:

• Refusal to sign the informed consent
• Subject presenting a cerebral localization of his lymphoma
• Contraindication to the realization of an MRI (metallic foreign body, pace-maker, cochlear implants)
• Claustrophobic subject
• Subject with a neurodegenerative disease (Parkinson's, Alzheimer's...)
• Subject with psychiatric disorders such as psychosis, except for anxiety-depressive episodes
• Subject with a systemic pathology with neurological manifestation
• Subject with a previous or evolving neurological pathology
• Subject with or with a history of severe head trauma (group 2 or 3 according to the Masters classification)
• Contraindication to the use of gadoline contrast products (severe renal insufficiency, liver transplantation, known or suspected hypersensitivity to the product)
• Pregnant or breastfeeding women
• Patient under tutelage
• Patient under curatorship
• Patient deprived of liberty
• Not a beneficiary of a social security system

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

Neurology department, Montpellier University Hospital

Montpellier, Occitanie, 34295, France

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Neurotoxicity Syndromes; Cytokine Release Syndrome

Interventions

Magnetic Resonance Spectroscopy; Contrast Media; Neuropsychological Tests

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Nervous System Diseases; Poisoning; Chemically-Induced Disorders; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Diagnostic Uses of Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals; Psychological Tests; Behavioral Disciplines and Activities

Study Officials

• Clarisse CARRA-DALLIERE, Dr

  Montpellier University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2022
• First Posted: August 22, 2022
• Study Start: September 22, 2022
• Primary Completion: September 13, 2023
• Study Completion: September 14, 2023
• Last Updated: August 9, 2024

Record last verified: 2024-08

Locations

FR (1)