Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12608000521325
Ethics application status
Approved
Date submitted
29/09/2008
Date registered
13/10/2008
Date last updated
6/09/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Epstein-Barr Virus (EBV) -specific T cells as therapy for relapsed / refractory EBV-positive lymphomas
Scientific title
Epstein-Barr Virus (EBV)-specific T cells as therapy for relapsed/refractory EBV-positive lymphomas
Secondary ID [1] 548 0
QIMR P1167 (The trial sponsor, the Queensland Institute of Medical Research is the issuing authority)
Universal Trial Number (UTN)
Trial acronym
EPL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed or refractory EBV-positive lymphoma 3073 0
Condition category
Condition code
Blood 3229 3229 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Autologous AdE1-Latent Membrane Protein (LMP) Cytotoxic T Lymphocytes. Dose, duration and mode of administration: total dose 20-800 million CTL given in 4 equal doses (each dose 5-200 million CTL) intravenously, at weekly intervals for the first cohort of 10 patients, and twice a week for the second cohort of ten patients.
Intervention code [1] 2815 0
Treatment: Other
Comparator / control treatment
None (single group, phase I study)
Control group
Uncontrolled

Outcomes
Primary outcome [1] 4111 0
Feasibility (generation of autologous clinical grade AdE1-LMP-specific Cytotoxic T Lymphocytes (CTL) from the blood of EBV-positive lymphoma patients)
Timepoint [1] 4111 0
The investigational product for each study participant will be assessed post production. Overall assessment when all study participants have received at least 1 treatment. The patient will have blood samples taken prior to and following each of infusion, and then at one, three, six and 12 months following the final infusion.
Primary outcome [2] 4112 0
Safety will be assessed by adverse event monitoring. Patients will be questioned and toxicities recorded according to the International Common Toxicity Criteria.
Timepoint [2] 4112 0
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
Primary outcome [3] 4113 0
Reconstitution of EBV-specific CTL immunity with anti-viral efficacy as a result of infusion of the investigational product. This will be measured by immunological and virological assessment of blood samples. Assays include immunophenotyping (using Major Histocompatibility Complex (MHC) class I peptide-specific tetramers), intracellular cytokine assays, CD107 cytotoxicity assays, and Epstein-Barr Virus deoxyribonucleic acid (EBV DNA) load analysis.
Timepoint [3] 4113 0
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 [1] 6925 0
Determination of the optimal dose intensity of the intervention. Optimal dose intensity will be assessed by comparing the clinical efficacy (as assessed by radiological assessment by Computerized Tomography), biological efficacy (as assessed by reconstitution of EBV-specific CTL immunity and anti-viral efficacy), safety and efficacy of the first schedule (4x weekly infusions) versus the second schedule (2x twice weekly infusions).
Timepoint [1] 6925 0
Clinical evaluation, adverse event monitoring and collection of blood samples for specialised tests will occur 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. Radiologic examination will occur at baseline and at 3 to 5 weeks and 3 months post the fourt treatment.
Secondary outcome [2] 6926 0
Clinical efficacy will be assessed by radiological assessement (as measured by Computerized Tomography) and clinical evaluation (history and physical examination).
Timepoint [2] 6926 0
Computerised Axial Tomography scan and additional scans at the physicican's discretion at baseline , 3-5 weeks post the 4th injection and 3 months post the 4th injection. Clinical evaluation 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

Eligibility
Key inclusion criteria
1 Informed consent.
2 EBV-positive lymphoma as determined by in situ hybridization or equivalent (excluding Burkitts Lymphoma).
3 Age 18 years or older.
4 Eastern Cooperative Oncology Group (ECOG) performance status 1, 2 or 3
5 Life expectancy of at least 6 months.
6 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.
7 No chemotherapy / radiotherapy and/or antibody therapy for at least 2 weeks prior to anticipated date of first infusion.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1 EBV negative tumour.
2 Presence of detectable malignant cells in the peripheral circulation by flow cytometry or morphology.
3 Serious infection within the past 28 days that has not adequately responded to therapy.
4 Pregnancy, or unwilling to use adequate contraception.
5 Serology (taken within 3 months of CTL release date) indicating active HBV or HCV infection, positive serology for HIV I&II, HTLV1 or syphilis.
6 Negative serology for EBV.
7 Psychiatric, addictive or any condition which may compromise the ability to participate in this trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
None
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
27/10/2008
Actual
23/10/2008
Date of last participant enrolment
Anticipated
Actual
21/09/2011
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 3320 0
Charities/Societies/Foundations
Name [1] 3320 0
The Atlantic Philanthropies Award
Country [1] 3320 0
Australia
Funding source category [2] 3322 0
Government body
Name [2] 3322 0
Queensland Smart State Award
Country [2] 3322 0
Australia
Funding source category [3] 3323 0
Charities/Societies/Foundations
Name [3] 3323 0
The Bristish Society for Haematology Award
Country [3] 3323 0
United Kingdom
Funding source category [4] 3324 0
Government body
Name [4] 3324 0
National Health and Medical Research Council (NHMRC) Project Grant
Country [4] 3324 0
Australia
Primary sponsor type
Government body
Name
Queensland Institute of Medical Research (QIMR)
Address
300 Herston Road Herston QLD 4006
Country
Australia
Secondary sponsor category [1] 2968 0
None
Name [1] 2968 0
Address [1] 2968 0
Country [1] 2968 0
Other collaborator category [1] 267 0
Hospital
Name [1] 267 0
Princess Alexandra Hospital
Address [1] 267 0
Ipswich Rd Wolloongabba QLD 4102
Country [1] 267 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5302 0
QIMR HREC
Ethics committee address [1] 5302 0
Ethics committee country [1] 5302 0
Australia
Date submitted for ethics approval [1] 5302 0
14/02/2008
Approval date [1] 5302 0
01/08/2008
Ethics approval number [1] 5302 0
EC00278
Ethics committee name [2] 6008 0
Princess Alexandra Hospital Human Research Ethics Committee
Ethics committee address [2] 6008 0
Ethics committee country [2] 6008 0
Australia
Date submitted for ethics approval [2] 6008 0
Approval date [2] 6008 0
08/08/2008
Ethics approval number [2] 6008 0
EC00167

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28543 0
Dr Maher Gandhi
Address 28543 0
Clinical Immunohaematology Laboratory, QIMR, 300 Herston Rd, Herston QLD 4006
Country 28543 0
Australia
Phone 28543 0
07 3845 3792
Fax 28543 0
07 3845 3510
Email 28543 0
[email protected]
Contact person for public queries
Name 11700 0
Dr Maher Gandhi
Address 11700 0
Clinical Immunohaematology Laboratory, QIMR, 300 Herston Rd, Herston QLD 4006
Country 11700 0
Australia
Phone 11700 0
07 3845 3792
Fax 11700 0
07 3845 3510
Email 11700 0
[email protected]
Contact person for scientific queries
Name 2628 0
Dr Maher Gandhi
Address 2628 0
Clinical Immunohaematology Laboratory, QIMR, 300 Herston Rd, Herston QLD 4006
Country 2628 0
Australia
Phone 2628 0
07 3845 3792
Fax 2628 0
07 3845 3510
Email 2628 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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