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

Primary Purpose

Epstein-Barr Virus Infections, Post-Transplant Lymphoproliferative Disorder, Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Group A
Group B
Sponsored by
Dr. Jean-Sebastien Delisle, MD, PhD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Epstein-Barr Virus Infections focused on measuring Allogeneic Transplantation, T cell, Epstein-Barr Virus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Hôpital Maisonneuve-RosemontRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Autologous or allogenic (stem cell donor) T cells

Allogeneic "third party" T cells

Arm Description

Subjects receive an autologous anti-EBV T-cell line or a T-cell line derived from the patient's allogeneic (stem cell transplant) donor.

Subjects receive a T-cell line from a matched or partially matched related donor.

Outcomes

Primary Outcome Measures

Safety: Incidence and description of CTCAE v.4.03 adverse events related to the experimental treatment
Complications: infusional toxicity, immune-related and other

Secondary Outcome Measures

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
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
All cause mortality
Within the 12 months observation period
Transplant-related outcomes
Incidence/severity of graft-versus-host disease, solid organ rejection episodes, relapse
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
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
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
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

Full Information

First Posted
October 15, 2015
Last Updated
March 13, 2023
Sponsor
Dr. Jean-Sebastien Delisle, MD, PhD
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1. Study Identification

Unique Protocol Identification Number
NCT02580539
Brief Title
A Study of the Safety and Efficacy of EBV Specific T-cell Lines
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 2015 (undefined)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Dr. Jean-Sebastien Delisle, MD, PhD

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epstein-Barr Virus Infections, Post-Transplant Lymphoproliferative Disorder, Lymphoma
Keywords
Allogeneic Transplantation, T cell, Epstein-Barr Virus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Autologous or allogenic (stem cell donor) T cells
Arm Type
Experimental
Arm Description
Subjects receive an autologous anti-EBV T-cell line or a T-cell line derived from the patient's allogeneic (stem cell transplant) donor.
Arm Title
Allogeneic "third party" T cells
Arm Type
Experimental
Arm Description
Subjects receive a T-cell line from a matched or partially matched related donor.
Intervention Type
Biological
Intervention Name(s)
Group A
Intervention Description
Peptide-stimulated T cells 2 x 10^7/m^2
Intervention Type
Biological
Intervention Name(s)
Group B
Intervention Description
Peptide-stimulated T cells per dose-escalation protocol
Primary Outcome Measure Information:
Title
Safety: Incidence and description of CTCAE v.4.03 adverse events related to the experimental treatment
Description
Complications: infusional toxicity, immune-related and other
Time Frame
During observation period (up to 42 days post infusion)
Secondary Outcome Measure Information:
Title
Changes in EBV titers (viral load) for each patient
Description
As measured by PCR weekly until week 6, at 3 months, 6 months and 12 months
Time Frame
Until 12 months post infusion
Title
Immune reconstitution as measured by various laboratory assays of immune cell type and function
Description
ELISpot on peripheral blood is assessed at the time points mentioned above
Time Frame
During observation period until 12 months post infusion
Title
All cause mortality
Description
Within the 12 months observation period
Time Frame
At 12 months
Title
Transplant-related outcomes
Description
Incidence/severity of graft-versus-host disease, solid organ rejection episodes, relapse
Time Frame
During observation period until 12 months post infusion
Title
Incidence/severity of graft-versus-host disease among patients who underwent stem cell transplantation
Description
Based on standardized assessments done weekly until week 6 and at 3, 6 and 12 months
Time Frame
During observation period until 12 months post infusion
Title
Number and severity of solid organ rejection episodes per patient among those who underwent solid organ transplant
Description
Based on standardized assessments done weekly until week 6 and at 3, 6 and 12 months
Time Frame
During observation period until 12 months post infusion
Title
Incidence of primary disease relapse among patients who underwent stem cell transplantation
Description
Based on standardized assessments done weekly until week 6 and at 3, 6 and 12 months
Time Frame
During observation period until 12 months post infusion
Title
Malignancy staging for patients with lymphoma, per internationally-accepted guidelines for the different specific lymphomas
Description
As clinically indicated by the investigators and/or primary physician
Time Frame
During observation period until 12 months post infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jean-Sebastien Delisle, MD,PhD
Phone
(514) 252-3404
Email
jsdelisle@umontreal.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Stephanie Thiant
Phone
(514) 252-4681
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Sebastien Delisle, MD,PhD
Organizational Affiliation
Maisonneuve-Rosemont Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Maisonneuve-Rosemont
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Sébastien Delisle, MD, PhD
Phone
5142523404
Email
js.delisle@umontreal.ca
First Name & Middle Initial & Last Name & Degree
Stéphanie Thiant, PhD
Phone
5142523404
Email
sthiant.hmr@ssss.gouv.qc.ca

12. IPD Sharing Statement

Links:
URL
https://ciusss-estmtl.gouv.qc.ca/propos/axes-dexcellence/therapie-cellulaire
Description
Center for Excellence in Cell Therapy

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

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