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

May 21, 2012 updated by: Maher Gandhi, Queensland Institute of Medical Research
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Queensland
      • Brisbane, Queensland, Australia, 4102
        • Princess Alexandra Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single group study
Autologous AdE1- Latent Membrane Protein (LMP) Cytotoxic T Lymphocytes.
Biological: Autologous AdE1- Latent Membrane Protein CTLs
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
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.
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
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
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
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 Measures

Outcome Measure
Time Frame
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.
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.
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Queensland Institute of Medical Research

Collaborators

National Health and Medical Research Council, Australia
Australian Department of Industry, Tourism and Resources
The Atlantic Philanthropies
British Society for Haematology

Investigators

  • Principal Investigator: Maher K Gandhi, MB CHB PhD, Queensland Institute of Medical Research

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (Actual)

January 1, 2012

Study Completion (Actual)

May 1, 2012

Study Registration Dates

First Submitted

October 22, 2008

First Submitted That Met QC Criteria

October 22, 2008

First Posted (Estimate)

October 24, 2008

Study Record Updates

Last Update Posted (Estimate)

May 22, 2012

Last Update Submitted That Met QC Criteria

May 21, 2012

Last Verified

May 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • QIMR P1167
  • ANZCTR12608000521325

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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