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

Lymphoma Clinical Trial

— EBV-TCL-01  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02580539
• Other study ID #: CER15020
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 2015
• Est. completion date: August 2024

Study information

• Verified date: March 2023
• Source: Maisonneuve-Rosemont Hospital
• Contact: Jean-Sebastien Delisle, MD,PhD
• Phone: (514) 252-3404
• Email: jsdelisle[@]umontreal.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Epstein-Barr Virus Infections
• Infections
• Lymphoma
• Lymphoproliferative Disorders
• Post-Transplant Lymphoproliferative Disorder

Intervention

Biological:
• Group A
Peptide-stimulated T cells 2 x 10^7/m^2
• Group B
Peptide-stimulated T cells per dose-escalation protocol

Locations

Country	Name	City	State
Canada	Hôpital Maisonneuve-Rosemont	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Dr. Jean-Sebastien Delisle, MD, PhD

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	All cause mortality	Within the 12 months observation period	At 12 months
Secondary	Transplant-related outcomes	Incidence/severity of graft-versus-host disease, solid organ rejection episodes, relapse	During observation period until 12 months post infusion
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Center for Excellence in Cell Therapy