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A Study of the Safety and Efficacy of EBV Specific T-cell Lines (EBV-TCL-01)

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: NCT02580539
Recruitment Status : Recruiting
First Posted : October 20, 2015
Last Update Posted : August 15, 2019
Sponsor:
Information provided by (Responsible Party):
Dr. Jean-Sebastien Delisle, MD, PhD, Maisonneuve-Rosemont Hospital

Brief Summary:
This study evaluates the safety and efficacy of EBV-specific T-cell lines to treat patients suffering from high EBV viral titers not responding to standard of care therapies and to treat EBV-related lymphoma. The study will recruit 6 patients to receive autologous T cells or a T cell line derived from the patient's allogeneic donor (in the case of stem cell transplant recipients), and 6 patients to receive a T-cell line prepared from a matched or partially matched related donor.

Condition or disease Intervention/treatment Phase
Epstein-Barr Virus Infections Post-Transplant Lymphoproliferative Disorder Lymphoma Biological: Group A Biological: Group B Phase 1 Phase 2

Detailed Description:

Epstein-Barr virus (EBV) is a member of the herpes virus family and infects up to 95% of individuals over their lifetime. Most initial infections occur in childhood and after a brief flu-like illness, the virus enters a phase of latency.

Patients who receive a bone marrow transplant or an organ transplant take medications drugs that weaken their immune systems. In these contexts, the virus can "reactivate" and cause very serious problems, such as lymphoma. For unknown reasons, people with a normal immune system can also develop lymphoma due to EBV.

The purpose of this study is to test the safety and efficacy of immune cells (T lymphocytes) that are specifically "taught" to recognize the virus-infected cells and to eliminate them. This "education" occurs is done over during a 2 weeks period (approximately), in the research laboratory. The cells are then transfused into the patient.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Open-label Study of the Safety and Efficacy of Epstein-Barr Virus Specific T-cell Lines for the Treatment of EBV Infection or EBV-related Lymphoproliferative Diseases
Study Start Date : November 2015
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020


Arm Intervention/treatment
Experimental: Autologous or allogenic (stem cell donor) T cells
Subjects receive an autologous anti-EBV T-cell line or a T-cell line derived from the patient's allogeneic (stem cell transplant) donor.
Biological: Group A
Peptide-stimulated T cells 2 x 10^7/m^2

Experimental: Allogeneic "third party" T cells
Subjects receive a T-cell line from a matched or partially matched related donor.
Biological: Group B
Peptide-stimulated T cells per dose-escalation protocol




Primary Outcome Measures :
  1. Safety: Incidence and description of CTCAE v.4.03 adverse events related to the experimental treatment [ Time Frame: During observation period (up to 42 days post infusion) ]
    Complications: infusional toxicity, immune-related and other


Secondary Outcome Measures :
  1. Changes in EBV titers (viral load) for each patient [ Time Frame: Until 12 months post infusion ]
    As measured by PCR weekly until week 6, at 3 months, 6 months and 12 months

  2. Immune reconstitution as measured by various laboratory assays of immune cell type and function [ Time Frame: During observation period until 12 months post infusion ]
    ELISpot on peripheral blood is assessed at the time points mentioned above

  3. All cause mortality [ Time Frame: At 12 months ]
    Within the 12 months observation period

  4. Transplant-related outcomes [ Time Frame: During observation period until 12 months post infusion ]
    Incidence/severity of graft-versus-host disease, solid organ rejection episodes, relapse

  5. Incidence/severity of graft-versus-host disease among patients who underwent stem cell transplantation [ Time Frame: During observation period until 12 months post infusion ]
    Based on standardized assessments done weekly until week 6 and at 3, 6 and 12 months

  6. Number and severity of solid organ rejection episodes per patient among those who underwent solid organ transplant [ Time Frame: During observation period until 12 months post infusion ]
    Based on standardized assessments done weekly until week 6 and at 3, 6 and 12 months

  7. Incidence of primary disease relapse among patients who underwent stem cell transplantation [ Time Frame: During observation period until 12 months post infusion ]
    Based on standardized assessments done weekly until week 6 and at 3, 6 and 12 months

  8. Malignancy staging for patients with lymphoma, per internationally-accepted guidelines for the different specific lymphomas [ Time Frame: During observation period until 12 months post infusion ]
    As clinically indicated by the investigators and/or primary physician



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Capacity to provide informed consent
  • Age ≥ 18 years old
  • Confirmed treatment-refractory EBV reactivation or EBV-related lymphoma
  • ECOG of 2 or less

Exclusion Criteria:

  • Medical condition requiring a corticosteroid dose greater than Prednisone 0.5mg/kg/day (or equivalent) at the time of the infusion.
  • Patient has received T-cell depleting antibodies or stem cell transplantation in the 28 days prior to proposed date of anti-EBV T-cell line infusion
  • Patient has received a solid organ transplant in the 3 months prior to proposed date of anti-EBV T-cell line infusion.
  • Pregnant or nursing females
  • Life expectancy of less than 3 months due to a condition unrelated to the EBV- related disease.
  • Active uncontrolled GVHD
  • Active uncontrolled SOT rejection episode

DONOR ELIGIBILITY: An allogeneic donor must be a first-degree relative with at least 3/6 HLA compatibility, have consented to donate peripheral blood mononuclear cells, and fulfill the same criteria for stem cell donation according to the hospital's standard operating procedure.


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): NCT02580539


Contacts
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Contact: Jean-Sebastien Delisle, MD,PhD (514) 252-3404 jsdelisle@umontreal.ca
Contact: Stephanie Thiant (514) 252-4681

Locations
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Canada, Quebec
Hôpital Maisonneuve-Rosemont Recruiting
Montreal, Quebec, Canada, H1T 2M4
Contact: Jean-Sébastien Delisle, MD, PhD    5142523404    js.delisle@umontreal.ca   
Contact: Stéphanie Thiant, PhD    5142523404    sthiant.hmr@ssss.gouv.qc.ca   
Sponsors and Collaborators
Dr. Jean-Sebastien Delisle, MD, PhD
Investigators
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Principal Investigator: Jean-Sebastine Delisle, MD,PhD Maisonneuve-Rosemont Hospital

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Responsible Party: Dr. Jean-Sebastien Delisle, MD, PhD, Clinician-Scientist, Hematopoietic Cell Transplantation Program, Maisonneuve-Rosemont Hospital
ClinicalTrials.gov Identifier: NCT02580539    
Other Study ID Numbers: CER15020
First Posted: October 20, 2015    Key Record Dates
Last Update Posted: August 15, 2019
Last Verified: August 2019
Keywords provided by Dr. Jean-Sebastien Delisle, MD, PhD, Maisonneuve-Rosemont Hospital:
Allogeneic Transplantation
T cell
Epstein-Barr Virus
Additional relevant MeSH terms:
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Infection
Epstein-Barr Virus Infections
Lymphoproliferative Disorders
Virus Diseases
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Herpesviridae Infections
DNA Virus Infections
Tumor Virus Infections