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

Sponsor
Dr. Jean-Sebastien Delisle, MD, PhD (Other)
Overall Status
Recruiting
CT.gov ID
NCT02580539
Collaborator
(none)
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Study Details

Study Description

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
  • 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.

Study Design

Study Type:
Interventional
Anticipated 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 :
Nov 1, 2015
Anticipated Primary Completion Date :
Aug 1, 2022
Anticipated Study Completion Date :
Aug 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Safety: Incidence and description of CTCAE v.4.03 adverse events related to the experimental treatment [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 [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 [During observation period until 12 months post infusion]

    ELISpot on peripheral blood is assessed at the time points mentioned above

  3. All cause mortality [At 12 months]

    Within the 12 months observation period

  4. Transplant-related outcomes [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 [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 [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 [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 [During observation period until 12 months post infusion]

    As clinically indicated by the investigators and/or primary physician

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Hôpital Maisonneuve-Rosemont Montreal Quebec Canada H1T 2M4

Sponsors and Collaborators

  • Dr. Jean-Sebastien Delisle, MD, PhD

Investigators

  • Principal Investigator: Jean-Sebastien Delisle, MD,PhD, Maisonneuve-Rosemont Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
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:
Oct 20, 2015
Last Update Posted:
Apr 6, 2022
Last Verified:
Apr 1, 2022
Keywords provided by Dr. Jean-Sebastien Delisle, MD, PhD, Clinician-Scientist, Hematopoietic Cell Transplantation Program, Maisonneuve-Rosemont Hospital
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 6, 2022