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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)

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ClinicalTrials.gov Identifier: NCT02912897
Recruitment Status : Not yet recruiting
First Posted : September 23, 2016
Last Update Posted : September 23, 2016
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital

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.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Other: Cellular therapy with EBV specific autologous CTL infusion Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : January 2017
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cellular therapy with EBV specific autologous CTL infusion Other: Cellular therapy with EBV specific autologous CTL infusion



Primary Outcome Measures :
  1. Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE [ Time Frame: 1 year ]


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 Swanton criteria At least 1 lesion detected in 2 or more following locations (sites) periventricular, juxtacortical, infratentorial, spinal cord
    • With a possible dissemination of MRI lesions in time based on the revised McDonald criteria1 i.e. at least simultaneous detection of one Gadolinium (Gd) enhancing asymptomatic lesion with at least one no Gd enhancing lesion
  • 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, or fungal infections.
  • Patients with white blood cell count (Leukocytes) < 750/mm3
  • Pregnant or breast feeding women
  • No effective 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02912897


Contacts
Contact: David LAPLAUD, Doctor + 33 (0)2 40 16 52 00 david.laplaud@univ-nantes.fr

Locations
France
University Hospital Not yet recruiting
Nantes, France
Contact: David LAPLAUD, Doctor    + 33 (0)2 40 16 52 00    david.laplaud@univ-nantes.fr   
Sponsors and Collaborators
Nantes University Hospital

Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT02912897     History of Changes
Other Study ID Numbers: RC14_0359
First Posted: September 23, 2016    Key Record Dates
Last Update Posted: September 23, 2016
Last Verified: September 2016

Keywords provided by Nantes University Hospital:
EBV-CTL
Multiple sclerosis
cellular therapy
clinically isolated syndrome

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases