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Trial registered on ANZCTR


Registration number
ACTRN12609000675224
Ethics application status
Approved
Date submitted
22/07/2009
Date registered
7/08/2009
Date last updated
21/10/2021
Date data sharing statement initially provided
21/10/2021
Date results information initially provided
21/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Killer T cell Therapy for Nasopharyngeal Carcinoma
Scientific title
Adoptive Immunotherapy for Epstein-Barr virus associated Nasopharyngeal Carcinoma
Secondary ID [1] 931 0
Queensland Institute of Medical Research project number P1069
Universal Trial Number (UTN)
Trial acronym
QHKUPNPC01
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epstein-Barr virus associated Nasopharyngeal Carcinoma 237284 0
Condition category
Condition code
Cancer 239611 239611 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
20-40 x 10^6 autologous Latent Membrane Protein Epstein-Barr Nuclear Antigen-1 (LMP/EBNA1) specific cytotoxic T lymphocytes (CTL) administered by fortnightly intravenous infusion. A minimum of 2 infusions and a maximum of 6 (subject to sufficient LMP-CTL being generated).
Intervention code [1] 236963 0
Treatment: Other
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 238403 0
Safety and tolerability: Safety of adoptive transfer will be monitored by blood tests to check full blood cell counts, biochemistry and liver function. Vital signs will be monitored and any adverse events will be recorded and treatment provided if required. A quality of life questionnaire will also assist in monitoring the tolerability of the adoptive transfer.
Timepoint [1] 238403 0
Safety and tolerability will be assessed through monitoring the patient on the day of each adoptive transfer - every 2 weeks for up to six transfers.
Secondary outcome [1] 244874 0
Efficacy:Efficacy will be assessed via immunological and virological monitoring - using Enzyme-linked immunosorbent spot (ELISPOT), tetramer and intracellular cytokine staining methods to measure CTL function ex vivo, and measuring Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) levels in the blood using real time polymerase chain reaction (PCR) to detect the BALF5 gene.

Efficacy will also be assessed via clinical monitoring. Reduction of tumour burden will be assessed via clinical examination and magnetic resonance imaging (MRI) and/or computed tomography (CT) scans
Timepoint [1] 244874 0
Post adoptive immunotherapy monitoring will be done at baseline, prior to each adoptive transfer (every 2 weeks for six transfers) and monthly until six months after the first adoptive transfer.

Reduction of tumour burden will be assessed at baseline and follow up scans will occur at 1, 2, 3, 4 & 6 months from the time of initial adoptive transfer.

Eligibility
Key inclusion criteria
1. Age 15 years or above.
2. Geographically accessible for follow up
3. Informed consent (from patient, or patient and parent/guardian if aged < 16 years) Approved hospital interpreters will be used for patients who do not have sufficient understanding of English for informed consent to be obtained without the use of an interpreter.
4. Eastern Cooperative Oncology Group performance status 0, 1, 2 or 3
5. Previously diagnosed with stage II, III or IV nasopharyngeal carcinoma (NPC)
6. Life expectancy of at least 3 months.
Minimum age
15 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. EBV negative tumour
2. Inability to identify an LMP/EBNA1 peptide to stimulate CTL cultures
3. Positive serology for human immunodeficiency virus (HIV)
4. Serology indicating active Hepititis B Virus (HBV) infection or carrier status for HBV (N.B. Positive serology for HBV indicating previous but cleared infection with HBV would not be an exclusion criteria.)
5. Serology indicating active Hepititis C Virus (HCV) infection
6. Significant non –malignant disease (e.g. severe cardiac or respiratory dysfunction)
7. Psychiatric, addictive or any conditions which may compromise the ability to participate in this trial
8. Prior cancers, except those diagnosed > 5 years ago with no evidence of disease recurrence and clinical expectation of recurrence of < 5%, or successfully treated non-melanoma skin cancer, or carcinoma in situ of the cervix.
9. Currently receiving immunosuppressive therapy, including corticosteroids.
10. Pregnancy, or unwilling to use adequate contraception.

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)
Not applicable (non randomised trial)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable (non randomised trial)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
There will be 2 treatment groups:
1.Patients with stage II, III and IV NPC in remission
2.Patients with stage II, III and IV NPC with refractory or recurrent disease
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
21/01/2008
Actual
12/11/2009
Date of last participant enrolment
Anticipated
Actual
15/07/2014
Date of last data collection
Anticipated
Actual
14/04/2016
Sample size
Target
50
Accrual to date
Final
30
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment outside Australia
Country [1] 1887 0
Hong Kong
State/province [1] 1887 0
Hong Kong

Funding & Sponsors
Funding source category [1] 237348 0
Government body
Name [1] 237348 0
Queensland Institute of Medical Research
Country [1] 237348 0
Australia
Primary sponsor type
University
Name
The University of Hong Kong
Address
Queen Mary Hospital
Pokfulam Road
Hong Kong
Country
Hong Kong
Secondary sponsor category [1] 236839 0
Government body
Name [1] 236839 0
Queensland Institute of Medical Research
Address [1] 236839 0
300 Herston Road
Herston
QLD
4006
Country [1] 236839 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239474 0
Institutional Review Board of the University of Hong Kong / Hospital Authority Hong Kong West Cluster
Ethics committee address [1] 239474 0
Room 901
Administration Block
Queen Mary Hospital
102 Pokfulam Road
Ethics committee country [1] 239474 0
Hong Kong
Date submitted for ethics approval [1] 239474 0
Approval date [1] 239474 0
07/02/2007
Ethics approval number [1] 239474 0
UW 07-032

Summary
Brief summary
Epstein-Barr virus (EBV) is associated with a number of human malignancies including nasopharyngeal carcinoma (NPC). 100% of undifferentiated NPC tumours are EBV- positive meaning the virus is localised to the tumour cells. We are attempting to develop immunotherapy as an alternate treatment for nasopharyngeal carcinoma (NPC) in addition to radiotherapy, chemotherapy and surgery. This immunotherapy would be in the form of adoptive transfer. This requires that a certain type of white blood cell found in the body known as “killer T-cells” or technically "cytotoxic T lymphocytes" (CTL) be isolated from the NPC patient’s own blood. These T cells are trained in the laboratory to become more efficient at recognising and destroying EBV infected tumour cells. Adoptive transfer is when the EBV-specific T cells are given back to the patient via intravenous infusions. This phase I adoptive immunotherapy trial aims to determine the safety, tolerability and efficacy of adoptive transfer of EBV specific T cells for NPC. The study will be carried out in collaboration with The University of Hong Kong, The Queensland Institute of Medical Research (QIMR) and The Princess Alexandra Hospital, Brisbane. A total of 50 eligible participants will be enrolled on the trial (35 from Hong Kong and 15 from the Princess Alexandra Hospital). Following informed consent, a 200-400ml blood sample will be collected from each participant and transported to the Q-Gen laboratory at QIMR in Brisbane where laboratory staff will begin to grow the T cells with a recombinant adenovirus. This process will take about 15 days. The recombinant adenovirus expresses small fragments from NPC-associated viral proteins this technique is used to stimulate the killer T cells in the laboratory. This adenovirus has been modified in such a way that it is non-infectious and does not cause any disease. This stimulation should result in the T cells being able to recognize EBV proteins on the NPC tumour that are there because of the EBV in the tumour. After recognising these proteins, the T cells will try to kill the tumour. After the killer T cells have been grown they will be purified and all residual adenovirus removed. They will be tested for safety, sterility and specific activity before being transported back to the treating hospital. The participants will undergo several baseline assessments, including blood tests. The killer T cells will be given back to the participant via adoptive transfer. Infusions of between 20-40 x 10^6 CTL will be given intravenously on a fortnightly basis, for up to six infusions. Participants will be monitored once a fortnight for the first 12 weeks and then once a month for four months. Monitoring will involve a series of blood tests and MRI scans. Participants will be on the trial for a total of 33 weeks.
Trial website
Trial related presentations / publications
1. Smith, C., et al., Pre-emptive and therapeutic adoptive immunotherapy for nasopharyngeal carcinoma: Phenotype and effector function of T cells impact on clinical response. Oncoimmunology, 2017. 6(2): p. e1273311.
2. Smith, C., et al., Effective treatment of metastatic forms of Epstein-Barr virus-associated nasopharyngeal carcinoma with a novel adenovirus-based adoptive immunotherapy. Cancer Res, 2012. 72(5): p. 1116-25.
Public notes

Contacts
Principal investigator
Name 29920 0
Prof Rajiv Khanna
Address 29920 0
QIMR 300 Herston Road Herston Brisbane Queensland 4006
Country 29920 0
Australia
Phone 29920 0
+61 7 3362 0385
Fax 29920 0
+61 7 3845 3510
Email 29920 0
[email protected]
Contact person for public queries
Name 13167 0
Katherine Matthews
Address 13167 0
QIMR
300 Herston Road
Herston
Brisbane
Queensland
4006
Country 13167 0
Australia
Phone 13167 0
+61 7 3362 0412
Fax 13167 0
+61 7 3845 3510
Email 13167 0
[email protected]
Contact person for scientific queries
Name 4095 0
Rajiv Khanna
Address 4095 0
QIMR
300 Herston Road
Herston
Brisbane
Queensland
4006
Country 4095 0
Australia
Phone 4095 0
+61 7 3362 0385
Fax 4095 0
+61 7 3845 3510
Email 4095 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Study finished pre these requirement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes 1. Smith, C., et al., Pre-emptive and t... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIEffective Treatment of Metastatic Forms of Epstein-Barr Virus–Associated Nasopharyngeal Carcinoma with a Novel Adenovirus-Based Adoptive Immunotherapy2012https://doi.org/10.1158/0008-5472.can-11-3399
Dimensions AIPre-emptive and therapeutic adoptive immunotherapy for nasopharyngeal carcinoma: Phenotype and effector function of T cells impact on clinical response2017https://doi.org/10.1080/2162402x.2016.1273311
EmbaseImmunotherapy Approaches Beyond PD-1 Inhibition: the Future of Cellular Therapy for Head and Neck Squamous Cell Carcinoma.2019https://dx.doi.org/10.1007/s11864-019-0630-9
EmbaseEBV-associated diseases: Current therapeutics and emerging technologies.2022https://dx.doi.org/10.3389/fimmu.2022.1059133
N.B. These documents automatically identified may not have been verified by the study sponsor.