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Trial registered on ANZCTR


Registration number
ACTRN12609000338268
Ethics application status
Approved
Date submitted
21/04/2009
Date registered
22/05/2009
Date last updated
26/03/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase I trial to assess safety of autologous Human Cytomegalovirus (HCMV) -specific T cell therapy for glioblastoma multiforme (GBM)
Scientific title
Phase I trial to assess safety of autologous Human Cytomegalovirus (HCMV)-specific T cell therapy for glioblastoma multiforme
Secondary ID [1] 551 0
QIMR P1228 (issued by the Queensland Institute for Medical Research)
Secondary ID [2] 552 0
QGMB01 (issued by Queensland Institute of Medical Research)
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
glioblastoma multiforme 3079 0
Condition category
Condition code
Cancer 3235 3235 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Autologous HCMV-specific T cell therapy administered by fortnightly intravenous infusion. A minimum of 3 infusions and a maximum of 4. The number of infusions will depend on the number of autologous HCMV-specific CTL generated. Between 25 to 40 x 106 cells are required per infusion.
Intervention code [1] 2820 0
Treatment: Other
Comparator / control treatment
None (phase I, single group trial)
Control group
Uncontrolled

Outcomes
Primary outcome [1] 5278 0
Feasibility, to demonstrate that autologous, clinical grade HCMV-specific T cells can be generated to clinical scale from the blood of GBM patients. Expanded CTL lines will be rigorously assessed for HCMV specificity using ELISPOT and Major Histocompatibility Comples (MHC)-peptide pentamers. In addition, the phenotype (CD3, CD4, CD8, CD56 and CD16) of the CTL lines will be analysed by Fluorescence Activated Cell Sorting (FACS) analysis. These T-cell cultures will be assessed for HCMV epitope-specific reactivity on days 14-15. Functional studies of the autologous HCMV-specific CTL will be performed in an appropriate laboratory.
Specifications of release of the investigational product:
1) >2 fold increase in HCMV-specific T cells as detected by intracellular cytokine assay
2) Phenotypic analysis of the culture, >60% CD3+ T cells, < 5% CD19+ B cells
3) Cell viability of >70%
Additionally, the cultures will be tested for sterility and mycoplasma by Q-Gen, the the investigational products manufacturing facility at the QIMR, at the time of cryopreservation of the cells and the product will not be released if sterility or mycoplasma testing fails.
A certificate of manufacture will be issued by Q-Gen when the products are released from the facility.
Timepoint [1] 5278 0
The investigational product for each study participant will be assessed post production. Overall assessment will be made when all study participants have received at least 1 treatment.
Primary outcome [2] 5279 0
to assess the safety and tolerability of infusion of clinical grade HCMV-specific T cells into HCMV-positive GBM patients
Timepoint [2] 5279 0
Safety and tolerability will be assessed by adverse event monitoring. Patients will be questioned and toxicities recorded according to the International Toxicity Criteria. Assessment will occur at screening/enrolment, baseline, pre and post each of the 4 fortnightly infusions and then at 1, 2, 3, 4, 6 and 12 months after the fourth infusion.
Secondary outcome [1] 8892 0
To monitor immunological and virological parameters. Laboratory assessment includes the frequency of Human Cytomegalovirus (HCMV)-specific Cytotoxic T Lymphocyte (CTL) measured by tetramer analysis, phenotyping, and Interferon (IFN) production in response to Human Cytomegalovirus (HCMV) peptide stimulation (Enzyme-linked immunosorbent spot (ELISPOT) assay or Interferon (IFN) intracellular cytokine staining). Additionally, the HCMV Deoxyribonucleic acid (DNA) levels in both the Peripheral Blood Mononuclear Cells (PBMC) and plasma will be measured by real time polymerase chain reaction (PCR).
Timepoint [1] 8892 0
Immunological and virological monitoring will occur at baseline, pre and post each of the 4 fortnightly infusions and then at 1, 2, 3, 4, 6 and 12 months after the fourth infusion.
Secondary outcome [2] 242129 0
To monitor clinical response to treatment. Clinical response will be assessed by Magnetic Resonance Imaging (MRI).
Timepoint [2] 242129 0
MRIs will be performed at baseline, 1, 2, 3, 4, and 6 months post the last treatment.

Eligibility
Key inclusion criteria
1. Age 18 years or above.
2. Geographically accessible for follow up
3. Informed consent.
4. ECOG (Eastern Cooperative Oncology Group) performance status 0, 1, 2 or 3
5. Life expectancy of at least 3 months
6. Previous histological diagnosis of GBM (WHO (World Health Organization) grade IV) and radiological and/or clinical evidence of tumour progression or recurrence
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. HCMV negative serology
2. Positive serology for HIV (Human Immunodefficiency Virus)
3. Serology indicating active HBV infection or carrier status for HBV.
4. Serology indicating active HCV infection
5. Significant non–malignant disease
6. Psychiatric, addictive or any conditions which may compromise the ability to participate in this trial
7. 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.
8. Receiving immunosuppressive therapy, including corticosteroids.
9. 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)
Not applicable (non randomised trial)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment postcode(s) [1] 657 0
4001

Funding & Sponsors
Funding source category [1] 3331 0
Charities/Societies/Foundations
Name [1] 3331 0
The Atlantic Philanthropies Award
Address [1] 3331 0
Administered by the sponsor, the Queensland Institute of Medical Research, 300 Herston Rd, Herston, Queensland 4006
Country [1] 3331 0
Australia
Funding source category [2] 4422 0
Government body
Name [2] 4422 0
Queensland Institute of Medical Research
Address [2] 4422 0
300 Herston Rd, Herston, Queensland 4006
Country [2] 4422 0
Australia
Primary sponsor type
Government body
Name
Queensland Institute of Medical Research
Address
300 Herston Rd Herston Queensland 4006
Country
Australia
Secondary sponsor category [1] 2977 0
None
Name [1] 2977 0
Address [1] 2977 0
Country [1] 2977 0
Other collaborator category [1] 270 0
Commercial sector/Industry
Name [1] 270 0
Briz Brain and Spine
Address [1] 270 0
St Andrew's Place, Suite 297, Level 1, 33 North St, Spring Hill Queensland 4000
Country [1] 270 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5342 0
Queensland Institute of Medical Research Human Research Ethics Committee (QIMR HREC)
Ethics committee address [1] 5342 0
300 Herston Rd, Herston Queensland 4006
Ethics committee country [1] 5342 0
Australia
Date submitted for ethics approval [1] 5342 0
19/11/2008
Approval date [1] 5342 0
11/06/2009
Ethics approval number [1] 5342 0
EC00278
Ethics committee name [2] 5343 0
Uniting Health Care Human Research Ethics Committee (HREC)
Ethics committee address [2] 5343 0
Toowong 4006
Ethics committee country [2] 5343 0
Australia
Date submitted for ethics approval [2] 5343 0
Approval date [2] 5343 0
23/06/2006
Ethics approval number [2] 5343 0
EC00374

Summary
Brief summary
This study looks at the safety and effectiveness of using T cell therapy targeting Human Cytomegalovirus (HCMV) in treating brain cancer (glioblastoma multiforme or GBM).

Who is it for?
You can join this study if you have brain cancer (glioblastoma multiforme) that has progressed or recurred since it was first diagnosed.

Trial details
Participants 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 is 4 fortnightly infusions, 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 and kill 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
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28547 0
Prof Rajiv Khanna
Address 28547 0
QIMR 300 Herston Rd Herston Brisbane Queensland 4006
Country 28547 0
Australia
Phone 28547 0
+61 7 3362 0385
Fax 28547 0
+61 7 3845 3510
Email 28547 0
Rajiv.Khanna@qimr.edu.au
Contact person for public queries
Name 11704 0
Dr Katherine Matthews
Address 11704 0
QIMR 300 Herston Rd Herston Brisbane Queensland 4006
Country 11704 0
Australia
Phone 11704 0
+61 7 3362 0412
Fax 11704 0
+61 7 3845 3510
Email 11704 0
Katherine.Matthews@qimr.edu.au
Contact person for scientific queries
Name 2632 0
Prof Rajiv Khanna
Address 2632 0
QIMR 300 Herston Rd Herston Brisbane Queensland 4006
Country 2632 0
Australia
Phone 2632 0
+61 7 3362 0385
Fax 2632 0
+61 7 3845 3510
Email 2632 0
Rajiv.Khanna@qimr.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary