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

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.

[title]Epstein-Barr Virus (EBV)-Specific T Cells as Therapy for Relapsed/Refractory EBV-Positive Lymphomas [conditions]

Lymphoma

[studytype]Interventional[studydesign]Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study [studydetails]

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]

Study arms and assigned interventions

Single group study: Experimental 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.

[studystart]October 2008 - October 2012[eligibility]

Ages eligible for study: 18 years and older
Genders eligible for study: Both
Accepts healthy volunteers: No

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

[enrolment]20[contact]

Maher K Gandhi
MBChB, PhD
61 7 3845 3792
maher.gandhi@qimr.edu.au

Rajiv Khanna
MSc, PhD
61 7 3362 0385
rajiv.khanna@qimr.edu.au