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

Lymphoma Clinical Trial

— EPL  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00779337
• Other study ID #: QIMR P1167
• Secondary ID: ANZCTR1260800052
• Status: Completed
• Phase: Phase 1
• First received: October 22, 2008
• Last updated: May 21, 2012
• Start date: October 2008
• Est. completion date: May 2012

Study information

• Verified date: May 2012
• Source: Queensland Institute of Medical Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: May 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma

Intervention

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.

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane	Queensland

Sponsors (5)

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

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Primary	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	Yes
Primary	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	No
Secondary	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.	Yes
Secondary	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	No