Actively Recruiting

Phase 1
Age: 18Years - 45Years
All Genders
NCT02912897

Trial to Assess the Safety and Feasibility of Adoptive Cell Therapy with Autologous EBV-specific Cytotoxic T Lymphocytes (CTL) in Patients with a First Clinical Episode Highly Suggestive of Multiple Sclerosis

Led by Nantes University Hospital · Updated on 2025-02-19

7

Participants Needed

1

Research Sites

405 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

The etiologic mechanisms involved in multiple sclerosis (MS) are not yet fully understood. Indeed MS is a multifactorial disease involving genetic and environmental factors and Epstein-Barr-Virus (EBV) could be one of these factors. However the link between EBV infection and the immunological mechanisms underlying MS is not clear. Robust sero-epidemiological evidences support an association between EBV infection and MS, and immunological data suggest an altered/deficient immune response against this virus. In healthy individuals EBV produces a persistent infection that is tightly controlled by the immune system. In patients with MS, cellular and humoral immune studies demonstrate an altered response against the virus with a T-cell abnormal reactivity against the EBV-infected autologous B-cells, elevated humoral immune response to Epstein Barr Nuclear Antigen-1, and in the case of children, an increased EBV shedding, demonstrating frequent EBV reactivations. Thus, it has been proposed, that patients with MS present a partially inefficient control of the EBV infection. Some experimental data support the hypothesis suggesting that the presence of autoreactive EBV-B cells in the meninges of patients, probably due to an insufficient clearance of these cells by the immune system, lead to the infiltration of autoreactive T cells. Another hypothesis also suggests a deficient control of the virus, in that case during the inactive phase of the disease. Together, the above data and hypotheses lead to the notion that an immune intervention capable of restoring the host-EBV balance could be beneficial to MS patients In this project, we will assess the feasibility and safety of autologous transfer of several amounts of CD8 T cells directed against autologous EBV transformed B cell lines, in order to finally restore an efficient control of EBV in MS patients. The main objective of the project is to test the feasibility and safety of the process, while efficacy parameters will be also assessed in secondary objectives.

CONDITIONS

Official Title

Trial to Assess the Safety and Feasibility of Adoptive Cell Therapy with Autologous EBV-specific Cytotoxic T Lymphocytes (CTL) in Patients with a First Clinical Episode Highly Suggestive of Multiple Sclerosis

Who Can Participate

Age: 18Years - 45Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age between 18 and 45 years
  • Patients with a clinically isolated syndrome (first acute or subacute neurological event consistent with demyelination such as optic neuritis, spinal cord syndrome, brainstem or cerebellar syndrome)
  • MRI showing dissemination of lesions in at least two of the following areas: periventricular, cortical or juxtacortical, infratentorial, spinal cord according to 2017 McDonald criteria
  • Possible dissemination in time evidenced by simultaneous detection of Gadolinium-enhancing and non-enhancing lesions
  • Or cerebrospinal fluid-specific oligoclonal bands present
  • Expanded Disability Status Scale (EDSS) score less than 3
  • Covered by health care insurance (social security)
  • Written informed consent obtained
  • Onset of symptoms within 60 days before inclusion
  • Negative tests for HIV, HTLV, Hepatitis B, C, and Syphilis within 30 days
  • Positive Epstein-Barr Virus serology
  • White blood cell count greater than 750/mm3
  • Negative pregnancy test
Not Eligible

You will not qualify if you...

  • Patients with clinically definite multiple sclerosis
  • Known infections with HIV, HTLV, Hepatitis A, B, C, or Syphilis, or active uncontrolled infections
  • White blood cell count less than 750/mm3
  • Pregnant or breastfeeding women
  • Women with childbearing potential not using effective contraception
  • Patients planning pregnancy during the study
  • Patients under legal guardianship
  • Participation in another clinical trial
  • Mental or psychiatric conditions preventing understanding of the trial
  • Medically unstable or health conditions impacting safety as determined by investigator
  • Stable conditions treated with immunotherapy
  • History of cancer within 5 years except surgically cured basal or cell skin lesions and in situ cervical cancer
  • Inability to comply with the study protocol
  • Contraindications for MRI or known hypersensitivity to contrast medium
  • Current treatment with immunosuppressive drugs including oral or systemic corticosteroids

AI-Screening

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Trial Site Locations

Total: 1 location

1

University Hospital

Nantes, France

Actively Recruiting

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Research Team

D

David LAPLAUD, Doctor

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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Trial to Assess the Safety and Feasibility of Adoptive Cell Therapy with Autologous EBV-specific Cytotoxic T Lymphocytes (CTL) in Patients with a First Clinical Episode Highly Suggestive of Multiple Sclerosis | DecenTrialz