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

This study has been completed.
Sponsor:
Collaborators:
The Atlantic Philanthropies
Australian Department of Industry, Tourism and Resources
British Society for Haematology
National Health and Medical Research Council, Australia
Information provided by (Responsible Party):
Maher Gandhi, Queensland Institute of Medical Research
ClinicalTrials.gov Identifier:
NCT00779337
First received: October 22, 2008
Last updated: May 21, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Lymphoma
Biological: Autologous AdE1- Latent Membrane Protein CTLs
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Epstein-Barr Virus (EBV)-Specific T Cells as Therapy for Relapsed/Refractory EBV-positive Lymphomas

Resource links provided by NLM:


Further study details as provided by Queensland Institute of Medical Research:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

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 [ 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. ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: October 2008
Study Completion Date: May 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00779337

Locations
Australia, Queensland
Princess Alexandra Hospital
Brisbane, Queensland, Australia, 4102
Sponsors and Collaborators
Queensland Institute of Medical Research
The Atlantic Philanthropies
Australian Department of Industry, Tourism and Resources
British Society for Haematology
National Health and Medical Research Council, Australia
Investigators
Principal Investigator: Maher K Gandhi, MB CHB PhD Queensland Institute of Medical Research
  More Information

No publications provided

Responsible Party: Maher Gandhi, Immunohaematology Laboratory Head, Queensland Institute of Medical Research
ClinicalTrials.gov Identifier: NCT00779337     History of Changes
Other Study ID Numbers: QIMR P1167, ANZCTR12608000521325
Study First Received: October 22, 2008
Last Updated: May 21, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Queensland Institute of Medical Research:
Epstein-Barr virus
lymphoma
immunotherapy

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on August 28, 2014