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

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma; Epstein-Barr Virus Infections; Post-Transplant Lymphoproliferative Disorder
• Intervention / Treatment: Biological: Group A; Biological: Group B

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 Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Hôpital Maisonneuve-Rosemont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in EBV titers (viral load) for each patient	As measured by PCR weekly until week 6, at 3 months, 6 months and 12 months	Until 12 months post infusion
Immune reconstitution as measured by various laboratory assays of immune cell type and function	ELISpot on peripheral blood is assessed at the time points mentioned above	During observation period until 12 months post infusion
All cause mortality	Within the 12 months observation period	At 12 months
Transplant-related outcomes	Incidence/severity of graft-versus-host disease, solid organ rejection episodes, relapse	During observation period until 12 months post infusion
Incidence/severity of graft-versus-host disease among patients who underwent stem cell transplantation	Based on standardized assessments done weekly until week 6 and at 3, 6 and 12 months	During observation period until 12 months post infusion
Number and severity of solid organ rejection episodes per patient among those who underwent solid organ transplant	Based on standardized assessments done weekly until week 6 and at 3, 6 and 12 months	During observation period until 12 months post infusion
Incidence of primary disease relapse among patients who underwent stem cell transplantation	Based on standardized assessments done weekly until week 6 and at 3, 6 and 12 months	During observation period until 12 months post infusion
Malignancy staging for patients with lymphoma, per internationally-accepted guidelines for the different specific lymphomas	As clinically indicated by the investigators and/or primary physician	During observation period until 12 months post infusion

Collaborators and Investigators

• Sponsor: Dr. Jean-Sebastien Delisle, MD, PhD
• Investigators: Principal Investigator: Jean-Sebastien Delisle, MD,PhD, Maisonneuve-Rosemont Hospital

Publications and helpful links

Helpful Links

• Center for Excellence in Cell Therapy

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): May 1, 2025
• Study Completion (Actual): May 1, 2025

Study Registration Dates

• First Submitted: October 15, 2015
• First Submitted That Met QC Criteria: October 19, 2015
• First Posted (Estimated): October 20, 2015

Study Record Updates

• Last Update Posted (Actual): May 14, 2025
• Last Update Submitted That Met QC Criteria: May 11, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Allogeneic Transplantation; T cell; Epstein-Barr Virus
• Additional Relevant MeSH Terms: Immune System Diseases; Virus Diseases; DNA Virus Infections; Lymphatic Diseases; Immunoproliferative Disorders; Herpesviridae Infections; Tumor Virus Infections; Infections; Lymphoproliferative Disorders; Epstein-Barr Virus Infections
• Other Study ID Numbers: CER15020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No