Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02912897
Recruitment Status : Recruiting
First Posted : September 23, 2016
Last Update Posted : January 28, 2021
Sponsor:
Information provided by (Responsible Party):
Nantes University Hospital

Tracking Information
First Submitted Date  ICMJE September 13, 2016
First Posted Date  ICMJE September 23, 2016
Last Update Posted Date January 28, 2021
Actual Study Start Date  ICMJE January 26, 2021
Estimated Primary Completion Date November 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 3, 2019)
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 21, 2016)
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE [ Time Frame: 1 year ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE Biological: Cellular therapy with EBV specific autologous CTL infusion
CTL infusions at D0, M3 and M6
Study Arms  ICMJE Experimental: Cellular therapy with EBV specific autologous CTL infusion
Intervention: Biological: Cellular therapy with EBV specific autologous CTL infusion
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 3, 2019)
7
Original Estimated Enrollment  ICMJE
 (submitted: September 21, 2016)
8
Estimated Study Completion Date  ICMJE November 2024
Estimated Primary Completion Date November 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: David LAPLAUD, Doctor + 33 (0)2 40 16 52 00 david.laplaud@univ-nantes.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02912897
Other Study ID Numbers  ICMJE RC14_0359
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nantes University Hospital
Study Sponsor  ICMJE Nantes University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Nantes University Hospital
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP