ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

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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 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]

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

Condition category

Condition code

Cancer

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]

Treatment: Other

Comparator / control treatment

None

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

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]

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]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD

Recruitment outside Australia

Country [1]

Hong Kong

State/province [1]

Hong Kong

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Queensland Institute of Medical Research

Address [1]

300 Herston Road
Herston
QLD
4006

Country [1]

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]

Government body

Name [1]

Queensland Institute of Medical Research

Address [1]

300 Herston Road
Herston
QLD
4006

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Institutional Review Board of the University of Hong Kong / Hospital Authority Hong Kong West Cluster

Ethics committee address [1]

Room 901
Administration Block
Queen Mary Hospital
102 Pokfulam Road

Ethics committee country [1]

Hong Kong

Date submitted for ethics approval [1]

Approval date [1]

07/02/2007

Ethics approval number [1]

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

Prof Rajiv Khanna

Address

QIMR 300 Herston Road Herston Brisbane Queensland 4006

Country

Australia

Phone

+61 7 3362 0385

Fax

+61 7 3845 3510

Rajiv.Khanna@qimr.edu.au

Contact person for public queries

Name

Katherine Matthews

Address

QIMR
300 Herston Road
Herston
Brisbane
Queensland
4006

Country

Australia

Phone

+61 7 3362 0412

Fax

+61 7 3845 3510

Katherine.Matthews@qimr.edu.au

Contact person for scientific queries

Name

Rajiv Khanna

Address

QIMR
300 Herston Road
Herston
Brisbane
Queensland
4006

Country

Australia

Phone

+61 7 3362 0385

Fax

+61 7 3845 3510

Rajiv.Khanna@qimr.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Dimensions AI	Effective Treatment of Metastatic Forms of Epstein-Barr Virus–Associated Nasopharyngeal Carcinoma with a Novel Adenovirus-Based Adoptive Immunotherapy	2012	https://doi.org/10.1158/0008-5472.can-11-3399
Dimensions AI	Pre-emptive and therapeutic adoptive immunotherapy for nasopharyngeal carcinoma: Phenotype and effector function of T cells impact on clinical response	2017	https://doi.org/10.1080/2162402x.2016.1273311
Embase	Immunotherapy Approaches Beyond PD-1 Inhibition: the Future of Cellular Therapy for Head and Neck Squamous Cell Carcinoma.	2019	https://dx.doi.org/10.1007/s11864-019-0630-9
Embase	EBV-associated diseases: Current therapeutics and emerging technologies.	2022	https://dx.doi.org/10.3389/fimmu.2022.1059133

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically