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

NCT00779337 | Completed Phase 1

• 2 other identifiers: QIMR P1167ANZCTR12608000521325
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Lymphoma

Keywords

Epstein-Barr virus; lymphoma; immunotherapy

Outcome Measures

Primary Outcomes (3)

• Feasibility (generation of autologous clinical grade AdE1-LMP-specific CTL from the blood of EBV-positive lymphoma patients)

  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.

  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.

  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 Outcomes (2)

• 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 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

  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

Study Arms (1)

Single group study

EXPERIMENTAL

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

Biological: Autologous AdE1- Latent Membrane Protein CTLs

Interventions

Autologous AdE1- Latent Membrane Protein CTLs BIOLOGICAL

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.

Single group study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Queensland Institute of Medical Research: lead
• The Atlantic Philanthropies: collaborator
• Australian Department of Industry, Tourism and Resources: collaborator
• British Society for Haematology: collaborator
• National Health and Medical Research Council, Australia: collaborator

Study Sites (1)

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

MeSH Terms

Conditions

Lymphoma; Epstein-Barr Virus Infections

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Study Officials

• Maher K Gandhi, MB CHB PhD

  Queensland Institute of Medical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Immunohaematology Laboratory Head

Study Record Dates

• First Submitted: October 22, 2008
• First Posted: October 24, 2008
• Study Start: October 1, 2008
• Primary Completion: January 1, 2012
• Study Completion: May 1, 2012
• Last Updated: May 22, 2012

Record last verified: 2012-05

Locations

AU (1)