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Trial registered on ANZCTR


Trial ID
ACTRN12613000838718
Ethics application status
Approved
Date submitted
22/07/2013
Date registered
30/07/2013
Date last updated
16/07/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
This study is assessing the safety and tolerability of using T cell therapy targeting Human Cytomegalovirus (HCMV) in treating brain cancer (glioblastoma multiforme or GBM) alongside standard treatment.
Scientific title
Phase I/II trial to assess safety and tolerability of autologous HCMV-specific T cell therapy as adjuvant treatment for glioblastoma multiforme.
Secondary ID [1] 282877 0
Nil
Universal Trial Number (UTN)
nil
Trial acronym
nil
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma multiforme (GBM) 289696 0
Condition category
Condition code
Cancer 290015 290015 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There will be a single treatment arm. Patients will be given up to six infusions every two to six weeks of 2x10e7 cells/m2 autologous HCMV-specific T cells by intravenous infusion. A minimum of 2 adoptive transfers will be given with the total number of infusions (up to a maximum of 6) dependent on the number of autologous HCMV-specific T cells generated.
Intervention code [1] 287579 0
Treatment: Other
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 290062 0
To assess the potential impact of adoptive T cell therapy on progression free survival

Assessed by: Clinical Evaluation, MRI
Timepoint [1] 290062 0
Clinical evaluation at baseline, at each adoptive transfer (2- 6 transfers, each 2-6 weeks apart) then at follow up 1, 2, 3, 4, 6 and 12 months after the last transfer . MRIs are done according to the clinical need and indication as directed by the treating clinicians. In general, MRIs are performed prior to diagnosis, after surgery and prior to radiotherapy, 1 month after radiotherapy, and every 2-3 months subsequently.
Primary outcome [2] 290063 0
To assess the safety and tolerability of adoptive immunotherapy for the treatment of HCMV-positive GBM to enable the development of immunotherapy as a treatment for HCMV-associated diseases. Assessed by: Clinical evaluation and adverse event monitoring, where participants will be questioned and toxicities recorded according to the common terminology for adverse events, safety blood tests, Functional Assessment of Cancer Therapy Brain Quality of Life Questionnaire.

Timepoint [2] 290063 0
Adverse events, safety blood tests and clinical evaluation are assessed at baseline, at each adoptive transfer (2-6 transfers, each 2-6 weeks apart) then at follow up 1, 2, 3, 4, 6 and 12 months after the last transfer. Quality of Life questionnaire at baseline, each adoptive transfer , then at follow up 1, 3, 6 and 12 months after the last transfer, and then 6 month intervals until study end (up to 3.5 years).

Secondary outcome [1] 303856 0
To determine whether adoptive immunotherapy with autologous T cell therapy will improve the overall survival. Overall survival is defined as the time from enrolment until death from progressive GBM.

Assessed by: MRI, clinical evaluation, safety bloods tests.
Timepoint [1] 303856 0
Clinical evaluation and blood tests at baseline, at each adoptive transfer (2-6 transfers, each 2-6 weeks apart) then at follow up 1, 2, 3, 4, 6 and 12 months after the last transfer.
MRIs are done according to the clinical need and indication as directed by the treating clinicians. In general, MRIs are performed prior to diagnosis, after surgery and prior to radiotherapy, 1 month after radiotherapy, and every 2-3 months subsequently.
Secondary outcome [2] 303932 0
In addition, immune functional and correlative studies (induction and persistence of CMV-specific immune response) will be also carried out.
Assessed by: immunological and virological blood tests.
Timepoint [2] 303932 0
Immunological and virological blood tests are at baseline, at each adoptive transfer, then at follow up 1, 2, 3, 4, 6 and 12 months after the last transfer, and then 6 month intervals until study end (up to 3.5 years).

Eligibility
Key inclusion criteria
1. Age 18 years or above
2. Informed consent. 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
3. ECOG performance status 0, 1, or 2
4. Life expectancy of at least 6 months
5. Histological diagnosis of GBM (WHO grade IV)
6. HCMV positive serology or positive staining for HCMV in tumour tissue
7. The patient will also complete the medical, and this will be co-signed by the clinical investigator
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Inability to identify an HCMV peptide to stimulate CTL cultures
2. Positive serology and NAT for HIV
3. Result indicating active HBV infection (N.B. Positive serology for HBV indicating previous but cleared infection with HBV would not be an exclusion criteria.)
4. Result indicating active HCV infection
5. Significant non–malignant disease (e.g. severe cardiac or respiratory dysfunction)
6. Psychiatric, addictive or any conditions which may compromise the ability to participate in this trial, as assessed by the clinical investigator
7. Prior cancers, except those diagnosed greater than 5 years ago with no evidence of disease recurrence and clinical expectation of recurrence of less than percent, or successfully treated nonmelanoma skin cancer, or carcinoma in situ of the cervix.
8. Receiving immunosuppressive therapy, except dexamethasone as given for normal management of symptoms related to their brain tumour and its treatment.
9. Lactating women, 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)
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
Nil
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
With an expected drop out rate of 10 percent and a sample size of 25, the effective sample size will be 23. Power calculations are generated based on the effective sample size of 23.

a) Safety and tolerability
The probability of observing at least one subject experience an adverse event in a sample of 23 subjects receiving the additional treatment (including 5 percent dropout) is 0.99, if the probability of that event occurring is assumed to be 0.2. If the proportion of people who experience an adverse event is greater than 0.5, we will be able to say with 80 percent power and 5 percent statistical significance, that the probability of an adverse event is greater than 0.2.

b) Efficacy
Previous studies have shown that the median time to recurrence is 6.9 months for newly diagnosed GBM patients. If we are to compare to the historical median progression free survival time of 6.9 months, our study based on 23 patients will allow us to conclude with 5 percent significance and 80 percent power that the therapy has increased median progression free survival time. This calculation is performed assuming an accrual time of 24 months and follow-up of 18 months. Furthermore, the results from this study will allow us to design an adequately powered Phase III trial.

Overall survival and progression free survival will be estimated using Kaplan-Meier method separately. Median Progression free survival will be determined using this methodology and 95 percent confidence interval will be calculated. Response rate and clinical benefit rate will be estimated with 95 percent confidence interval. Survival curves will be estimated by the Kaplan-Meier method and differences will be tested using log-rank test statistics, p values less than 0.05 will be considered statistically significant.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 1353 0
The Wesley Hospital - Auchenflower

Funding & Sponsors
Funding source category [1] 287662 0
Charities/Societies/Foundations
Name [1] 287662 0
QIMR Berghofer Medical Research Institute
Address [1] 287662 0
300 Herston Road, Herston, Brisbane, QLD, 4006
Country [1] 287662 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
QIMR Berghofer Medical Research Institute
Address
300 Herston Road, Herston, Brisbane, QLD, 4006
Country
Australia
Secondary sponsor category [1] 286400 0
None
Name [1] 286400 0
Address [1] 286400 0
Country [1] 286400 0
Other collaborator category [1] 277533 0
Individual
Name [1] 277533 0
Professor David Walker
Address [1] 277533 0
Wesley Hospital, Evan Thomson Building, Level 10 Chasely Street Auchenflower, QLD 4066
Country [1] 277533 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289625 0
QIMR Berghofer Medical Research Institute Human Research Ethics Committee
Ethics committee address [1] 289625 0
QIMR Berghofer Medical Research Institute HREC
QIMR Berghofer Medical Research Institute
300 Herston Rd
Herston QLD 4006
Ethics committee country [1] 289625 0
Australia
Date submitted for ethics approval [1] 289625 0
Approval date [1] 289625 0
28/06/2013
Ethics approval number [1] 289625 0
P1485

Summary
Brief summary
This study is assessing the efficacy, safety and tolerability of using T cell therapy targeting human cytomegalovirus (HCMV) in treating brain cancer (glioblastoma multiforme ).

Who is it for?
You may be eligible to join this study if you are aged 18 years or above, have been diagnosed with glioblastoma multiforme , and have not yet begun standard treatment for this disease .

Trial details:
Patients will be eligible if they have been recently diagnosed with glioblastoma multiforme and are about to begin standard radiotherapy and chemotherapy regimens. A blood sample will be taken from patients prior to beginning standard radiotherapy and chemotherapy, in order to grow the cells for the experimental therapy. These cells, known as T cells (a type of white blood cell) will be grown in the laboratory from each patient’s blood sample. After completing standard radiotherapy and chemotherapy regimens, all participants in this study will receive treatment with killer T cells (a type of white blood cell) which have been grown in the laboratory from the participant’s own white blood cells. Treatment consists of up to 6 infusions of T cells (given fortnightly or monthly, depending on the standard treatment regimen), and patients are monitored for 12 months afterwards to see if treatment is safe and to measure any reduction in tumour and amount of virus in the blood.

Recent studies suggest that most gliomas carry a common virus, called human cytomegalovirus (HCMV), which is normally controlled by killer T cells. The study aims to see if killer T cells grown in the laboratory and trained to recognise components of the virus can also kill HCMV infected gliomas. The standard first-line treatment is usually surgery, radiotherapy and a chemotherapy drug called temozolomide. If the cancer then grows back, there are no known effective treatments.
Trial website
Nil
Trial related presentations / publications
Nil
Public notes

Contacts
Principal investigator
Name 41626 0
Prof Rajiv Khanna
Address 41626 0
QIMR Berghofer Medical Research Institute. 300 Herston Rd Herston QLD 4006
Country 41626 0
Australia
Phone 41626 0
+61 7 3362 0385
Fax 41626 0
+61 7 3845 3510
Email 41626 0
Rajiv.Khanna@qimrberghofer.edu.au
Contact person for public queries
Name 41627 0
Dr Katherine Matthews
Address 41627 0
QIMR Berghofer Medical Research Institute. 300 Herston Rd Herston QLD 4006
Country 41627 0
Australia
Phone 41627 0
+61 7 3362 0412
Fax 41627 0
+61 7 3845 3510
Email 41627 0
immunotherapy@qimrberghofer.edu.au
Contact person for scientific queries
Name 41628 0
Prof Rajiv Khanna
Address 41628 0
QIMR Berghofer Medical Research Institute. 300 Herston Rd Herston QLD 4006
Country 41628 0
Australia
Phone 41628 0
+61 7 3362 0385
Fax 41628 0
+61 7 3845 3510
Email 41628 0
Rajiv.Khanna@qimrberghofer.edu.au