Clinical trial NCT02580539: A Study of the Safety and Efficacy of EBV Specific T-cell Lines
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Epstein-Barr Virus Infections
Post-Transplant Lymphoproliferative Disorder
Lymphoma
Keywords: Allogeneic Transplantation
T cell
Epstein-Barr Virus
Lead sponsor: Maisonneuve-Rosemont Hospital
Sponsor class: OTHER
First posted: 2015-10-20
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Safety: Incidence and description of CTCAE v.4.03 adverse events related to the experimental treatment
timeFrame: During observation period (up to 42 days post infusion)
Secondary outcomes:
measure: Changes in EBV titers (viral load) for each patient
timeFrame: Until 12 months post infusion
measure: Immune reconstitution as measured by various laboratory assays of immune cell type and function
timeFrame: During observation period until 12 months post infusion
measure: All cause mortality
timeFrame: At 12 months
measure: Transplant-related outcomes
timeFrame: During observation period until 12 months post infusion
measure: Incidence/severity of graft-versus-host disease among patients who underwent stem cell transplantation
timeFrame: During observation period until 12 months post infusion
measure: Number and severity of solid organ rejection episodes per patient among those who underwent solid organ transplant
timeFrame: During observation period until 12 months post infusion
measure: Incidence of primary disease relapse among patients who underwent stem cell transplantation
timeFrame: During observation period until 12 months post infusion
measure: Malignancy staging for patients with lymphoma, per internationally-accepted guidelines for the different specific lymphomas
timeFrame: During observation period until 12 months post infusion
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Hôpital Maisonneuve-Rosemont
state: Quebec
Study officials:
affiliation: Maisonneuve-Rosemont Hospital
name: Jean-Sebastien Delisle, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: