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

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ClinicalTrials.gov Identifier: NCT02580539
Recruitment Status : Recruiting
First Posted : October 20, 2015
Last Update Posted : September 11, 2020
Sponsor:
Information provided by (Responsible Party):
Dr. Jean-Sebastien Delisle, MD, PhD, Maisonneuve-Rosemont Hospital

Tracking Information
First Submitted Date  ICMJE October 15, 2015
First Posted Date  ICMJE October 20, 2015
Last Update Posted Date September 11, 2020
Study Start Date  ICMJE November 2015
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 19, 2015)
Safety: Incidence and description of CTCAE v.4.03 adverse events related to the experimental treatment [ Time Frame: During observation period (up to 42 days post infusion) ]
Complications: infusional toxicity, immune-related and other
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2019)
  • Changes in EBV titers (viral load) for each patient [ Time Frame: Until 12 months post infusion ]
    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 [ Time Frame: During observation period until 12 months post infusion ]
    ELISpot on peripheral blood is assessed at the time points mentioned above
  • All cause mortality [ Time Frame: At 12 months ]
    Within the 12 months observation period
  • Transplant-related outcomes [ Time Frame: During observation period until 12 months post infusion ]
    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 [ Time Frame: During observation period until 12 months post infusion ]
    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 [ Time Frame: During observation period until 12 months post infusion ]
    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 [ Time Frame: During observation period until 12 months post infusion ]
    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 [ Time Frame: During observation period until 12 months post infusion ]
    As clinically indicated by the investigators and/or primary physician
Original Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2015)
  • Changes in EBV titers (viral load) for each patient [ Time Frame: Until 12 months post infusion ]
  • Immune reconstitution as measured by various laboratory assays of immune cell type and function [ Time Frame: During observation period until 12 months post infusion ]
  • All cause mortality [ Time Frame: At 12 months ]
  • Transplant-related outcomes [ Time Frame: During observation period until 12 months post infusion ]
    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 [ Time Frame: 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 [ Time Frame: During observation period until 12 months post infusion ]
  • Incidence of primary disease relapse among patients who underwent stem cell transplantation [ Time Frame: During observation period until 12 months post infusion ]
  • Malignancy staging for patients with lymphoma, per internationally-accepted guidelines for the different specific lymphomas [ Time Frame: During observation period until 12 months post infusion ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Safety and Efficacy of EBV Specific T-cell Lines
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Epstein-Barr Virus Infections
  • Post-Transplant Lymphoproliferative Disorder
  • Lymphoma
Intervention  ICMJE
  • Biological: Group A
    Peptide-stimulated T cells 2 x 10^7/m^2
  • Biological: Group B
    Peptide-stimulated T cells per dose-escalation protocol
Study Arms  ICMJE
  • 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.
    Intervention: Biological: Group A
  • Experimental: Allogeneic "third party" T cells
    Subjects receive a T-cell line from a matched or partially matched related donor.
    Intervention: Biological: Group B
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 19, 2015)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2022
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Jean-Sebastien Delisle, MD,PhD (514) 252-3404 jsdelisle@umontreal.ca
Contact: Stephanie Thiant (514) 252-4681
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02580539
Other Study ID Numbers  ICMJE CER15020
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr. Jean-Sebastien Delisle, MD, PhD, Maisonneuve-Rosemont Hospital
Study Sponsor  ICMJE Dr. Jean-Sebastien Delisle, MD, PhD
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jean-Sebastine Delisle, MD,PhD Maisonneuve-Rosemont Hospital
PRS Account Maisonneuve-Rosemont Hospital
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP