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Epstein-Barr Virus (EBV)-Specific T Cells as Therapy for Relapsed/Refractory EBV-positive Lymphomas (EPL)

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
Autologous AdE1- Latent Membrane Protein CTLs
Sponsored by
Queensland Institute of Medical Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring Epstein-Barr virus, lymphoma, immunotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Informed consent.
  • EBV-positive lymphoma as determined by in situ hybridization or equivalent (excluding Burkitts Lymphoma).
  • Age 18 years or older.
  • ECOG performance status 1, 2 or 3
  • Life expectancy of at least 6 months.
  • Measurable disease: either relapsing, partially responsive, refractory or progressive disease, includes disease detected either by clinical examination, radiographic evaluation (including CT scans, and at physician's discretion by functional imaging), or a persistently detectable plasma EBV viral load.
  • No chemotherapy / radiotherapy and/or antibody therapy for at least 2 weeks prior to anticipated date of first infusion.

Exclusion Criteria:

  • EBV negative tumour
  • Presence of detectable malignant cells in the peripheral circulation by flow cytometry or morphology
  • Serious infection within the past 28 days that has not adequately responded to therapy
  • Pregnancy, or unwilling to use adequate contraception
  • Serology (taken within 3 months of CTL release date) indicating active HBV or HCV infection, positive serology for HIV I&II, HTLV1 or syphilis
  • Negative serology for EBV
  • Psychiatric, addictive or any condition which may compromise the ability to participate in this trial

Sites / Locations

  • Princess Alexandra Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single group study

Arm Description

Autologous AdE1- Latent Membrane Protein (LMP) Cytotoxic T Lymphocytes.

Outcomes

Primary Outcome Measures

Feasibility (generation of autologous clinical grade AdE1-LMP-specific CTL from the blood of EBV-positive lymphoma patients)
Safety as assessed by adverse event monitoring. Patients will be questioned and toxicities recorded according to the International Common Toxicity Criteria.
Reconstitution of EBV-specific CTL immunity with anti-viral efficacy measured by immunological & virological assessment of blood samples including immunophenotyping, intracellular cytokine assays, CD107 cytotoxicity assays and EBV DNA load analysis.

Secondary Outcome Measures

Optimal dose intensity of the intervention. Clinical efficacy (radiological assessment by CT), biological efficacy (reconstitution of EBV-specific CTL immunity & anti-viral efficacy), safety & efficacy of the 1st treatment schedule vs the 2nd schedule
Clinical efficacy

Full Information

First Posted
October 22, 2008
Last Updated
May 21, 2012
Sponsor
Queensland Institute of Medical Research
Collaborators
The Atlantic Philanthropies, Australian Department of Industry, Tourism and Resources, British Society for Haematology, National Health and Medical Research Council, Australia
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1. Study Identification

Unique Protocol Identification Number
NCT00779337
Brief Title
Epstein-Barr Virus (EBV)-Specific T Cells as Therapy for Relapsed/Refractory EBV-positive Lymphomas
Acronym
EPL
Official Title
Epstein-Barr Virus (EBV)-Specific T Cells as Therapy for Relapsed/Refractory EBV-positive Lymphomas
Study Type
Interventional

2. Study Status

Record Verification Date
May 2012
Overall Recruitment Status
Completed
Study Start Date
October 2008 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
May 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Queensland Institute of Medical Research
Collaborators
The Atlantic Philanthropies, Australian Department of Industry, Tourism and Resources, British Society for Haematology, National Health and Medical Research Council, Australia

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This trial will use a new method of treating lymphoma using a therapy derived from a person's Killer T cells. These Killer T cells are taken from a person's blood and grown in a test tube to increase the number of these cells that are specifically active against the lymphoma cells. The cells are then given to the patient by intravenous infusion with the aim of killing the lymphoma cells. Potentially this treatment will help to kill the residual/recurrent tumour that is present after other lymphoma treatment and reduce the chance of the tumour recurring.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
Epstein-Barr virus, lymphoma, immunotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single group study
Arm Type
Experimental
Arm Description
Autologous AdE1- Latent Membrane Protein (LMP) Cytotoxic T Lymphocytes.
Intervention Type
Biological
Intervention Name(s)
Autologous AdE1- Latent Membrane Protein CTLs
Intervention Description
Total dose 20-800 million CTL given in 4 equal doses (5-200 million CTL) given intravenously, at weekly intervals for the first cohort of 10 patients and twice a week for the second cohort of 10 patients.
Primary Outcome Measure Information:
Title
Feasibility (generation of autologous clinical grade AdE1-LMP-specific CTL from the blood of EBV-positive lymphoma patients)
Time Frame
The investigational product for each participant will be assessed post production. The patient will have blood samples taken prior to and following each infusion, and then at 1, 3, 6 & 12 months following the final infusion.
Title
Safety as assessed by adverse event monitoring. Patients will be questioned and toxicities recorded according to the International Common Toxicity Criteria.
Time Frame
1 hour post 4 AdE1-LMP CTL injections (injections are weekly for first 10 participants & twice weekly for the next 10 participants), 3-5 weeks post the 4th injection, then 3, 6 and 12 months post the 4th injection
Title
Reconstitution of EBV-specific CTL immunity with anti-viral efficacy measured by immunological & virological assessment of blood samples including immunophenotyping, intracellular cytokine assays, CD107 cytotoxicity assays and EBV DNA load analysis.
Time Frame
At baseline, pre and 1 hour post 4 AdE1-LMP CTL injections, 3-5 weeks post the 4th injection, then 3, 6 and 12 months post the 4th injection
Secondary Outcome Measure Information:
Title
Optimal dose intensity of the intervention. Clinical efficacy (radiological assessment by CT), biological efficacy (reconstitution of EBV-specific CTL immunity & anti-viral efficacy), safety & efficacy of the 1st treatment schedule vs the 2nd schedule
Time Frame
Clinical evaluation, AE monitoring & collection of blood samples at baseline, pre & 1 hr post injections, 3-5 weeks, 3, 6 and 12 months post 4th injection. Radiological examination at baseline & at 3 to 5 wks & 3 months post the 4th treatment.
Title
Clinical efficacy
Time Frame
CT scan +/- additional scans at baseline , 3-5 weeks & 3 months post the 4th injection. Clinical evaluation at baseline, pre and 1 hour post injections, 3-5 weeks, 3, 6 and 12 months post the 4th injection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Informed consent. EBV-positive lymphoma as determined by in situ hybridization or equivalent (excluding Burkitts Lymphoma). Age 18 years or older. ECOG performance status 1, 2 or 3 Life expectancy of at least 6 months. Measurable disease: either relapsing, partially responsive, refractory or progressive disease, includes disease detected either by clinical examination, radiographic evaluation (including CT scans, and at physician's discretion by functional imaging), or a persistently detectable plasma EBV viral load. No chemotherapy / radiotherapy and/or antibody therapy for at least 2 weeks prior to anticipated date of first infusion. Exclusion Criteria: EBV negative tumour Presence of detectable malignant cells in the peripheral circulation by flow cytometry or morphology Serious infection within the past 28 days that has not adequately responded to therapy Pregnancy, or unwilling to use adequate contraception Serology (taken within 3 months of CTL release date) indicating active HBV or HCV infection, positive serology for HIV I&II, HTLV1 or syphilis Negative serology for EBV Psychiatric, addictive or any condition which may compromise the ability to participate in this trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maher K Gandhi, MB CHB PhD
Organizational Affiliation
Queensland Institute of Medical Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
Princess Alexandra Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia

12. IPD Sharing Statement

Learn more about this trial

Epstein-Barr Virus (EBV)-Specific T Cells as Therapy for Relapsed/Refractory EBV-positive Lymphomas

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