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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 (MS and EBV-CTL)

Primary Purpose

Multiple Sclerosis

Status
Recruiting
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Cellular therapy with EBV specific autologous CTL infusion
Sponsored by
Nantes University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring EBV-CTL, Multiple sclerosis, cellular therapy

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 18<Age≤45 years

  • Patients with :

    • A clinically isolated syndrome (first acute or sub acute neurological event consistent with demyelination [i.e. optic neuritis, spinal cord syndrome, brainstem/ cerebellar syndrome])
    • And a MRI scan showing dissemination of MRI lesions in space based on 2017 McDonald criteria At least 1 lesion detected in 2 or more following locations (sites) periventricular, cortical or juxtacortical, infratentorial, spinal cord
    • With a possible dissemination in time based on the revised McDonald cirteria and evicenced on simultaneous detection of one Gadolinium (Gd) enhancing and non-Gd enhancing lesions
    • Or demonstration of CSF-specific oligoclonal bands (OCBs)
  • EDSS Score <3
  • Patients covered by health care insurance (social security)
  • Written informed consent obtained.
  • Onset of symptoms occurring within 60 days of inclusion
  • Patients with HIV, HTLV, Hepatitis B, C Syphilis testing negative within 30 days
  • Positive EBV serology
  • White blood cell count (Leukocytes) > 750/mm3
  • Negative pregnancy test

Exclusion Criteria:

  • Patients with clinically definite multiple sclerosis
  • Patients known to have HIV, HTLV Hepatitis A, B, C or Syphilis infections or patient with active uncontrolled systemic bacterial, viral, parasitic or fungal infections.
  • Patients with white blood cell count (Leukocytes) < 750/mm3
  • Pregnant or breast feeding women
  • Patient with childbearing potentiel refusing efficient contraceptive method
  • Patients wishing to be pregnant during the course of the study
  • Patients under legal guardianship
  • Concomitant participation of any other trial
  • Patients with mental or psychiatry condition unable to understand the trial
  • Patients with any medically unstable condition or any health conditions that may impact the safety of the patient as determined by the investigator or patient with any stable condition treated with immunotherapy
  • Patients with a history of cancer within 5 years or progressive cancer except for basal or cell skin lesions surgically excised and cured, in situ cervical cancer
  • Patients unable to comply with protocol.
  • Contraindication for MRI or/and any known history of hypersensitivity to contrast medium
  • Patients currently treated with immunosuppressive drugs including oral or systemic corticosteroids

Sites / Locations

  • University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cellular therapy with EBV specific autologous CTL infusion

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE

Secondary Outcome Measures

Full Information

First Posted
September 13, 2016
Last Updated
April 5, 2023
Sponsor
Nantes University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02912897
Brief 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
Acronym
MS and EBV-CTL
Official Title
An Open Single-center, Phase I Proof of Concept 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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 26, 2021 (Actual)
Primary Completion Date
November 2026 (Anticipated)
Study Completion Date
November 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nantes University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
EBV-CTL, Multiple sclerosis, cellular therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cellular therapy with EBV specific autologous CTL infusion
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Cellular therapy with EBV specific autologous CTL infusion
Intervention Description
CTL infusions at D0, M3 and M6
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 18<Age≤45 years Patients with : A clinically isolated syndrome (first acute or sub acute neurological event consistent with demyelination [i.e. optic neuritis, spinal cord syndrome, brainstem/ cerebellar syndrome]) And a MRI scan showing dissemination of MRI lesions in space based on 2017 McDonald criteria At least 1 lesion detected in 2 or more following locations (sites) periventricular, cortical or juxtacortical, infratentorial, spinal cord With a possible dissemination in time based on the revised McDonald cirteria and evicenced on simultaneous detection of one Gadolinium (Gd) enhancing and non-Gd enhancing lesions Or demonstration of CSF-specific oligoclonal bands (OCBs) EDSS Score <3 Patients covered by health care insurance (social security) Written informed consent obtained. Onset of symptoms occurring within 60 days of inclusion Patients with HIV, HTLV, Hepatitis B, C Syphilis testing negative within 30 days Positive EBV serology White blood cell count (Leukocytes) > 750/mm3 Negative pregnancy test Exclusion Criteria: Patients with clinically definite multiple sclerosis Patients known to have HIV, HTLV Hepatitis A, B, C or Syphilis infections or patient with active uncontrolled systemic bacterial, viral, parasitic or fungal infections. Patients with white blood cell count (Leukocytes) < 750/mm3 Pregnant or breast feeding women Patient with childbearing potentiel refusing efficient contraceptive method Patients wishing to be pregnant during the course of the study Patients under legal guardianship Concomitant participation of any other trial Patients with mental or psychiatry condition unable to understand the trial Patients with any medically unstable condition or any health conditions that may impact the safety of the patient as determined by the investigator or patient with any stable condition treated with immunotherapy Patients with a history of cancer within 5 years or progressive cancer except for basal or cell skin lesions surgically excised and cured, in situ cervical cancer Patients unable to comply with protocol. Contraindication for MRI or/and any known history of hypersensitivity to contrast medium Patients currently treated with immunosuppressive drugs including oral or systemic corticosteroids
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David LAPLAUD, Doctor
Phone
+ 33 (0)2 40 16 52 00
Email
david.laplaud@univ-nantes.fr
Facility Information:
Facility Name
University Hospital
City
Nantes
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David LAPLAUD, Doctor
Phone
+ 33 (0)2 40 16 52 00
Email
david.laplaud@univ-nantes.fr

12. IPD Sharing Statement

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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

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