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

Dr. Jean-Sebastien Delisle, MD, PhD12 enrolled

Overview

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.

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Epstein-Barr Virus Infections

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Safety: Incidence and description of CTCAE v.4.03 adverse events related to the experimental treatment

Complications: infusional toxicity, immune-related and other

Time frame: During observation period (up to 42 days post infusion)

Secondary Outcomes

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

Time frame: 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