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Trial registered on ANZCTR

Registration number
Ethics application status
Date submitted
Date registered
Date last updated
Type of registration
Prospectively registered

Titles & IDs
Public title
MGMT Gene Therapy and Chemotherapy for the treatment of Childhood Brain Tumours
Scientific title
In paediatric patients with high risk brain tumours, is it safe and feasible to infuse autologous Peripheral Blood Stem Cells transduced with a mutant MGMT Gene?
Secondary ID [1] 280425 0
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Childhood Brain Tumours 286392 0
Condition category
Condition code
Cancer 286643 286643 0 0

Study type
Description of intervention(s) / exposure
1. Participants will be given a single dose of BCNU (600 mg/m^2, IV infusion) 48 to 56 hours before infusion of gene modified bone marrow stem cells. Patients who have had prior craniospinal radiotherapy will not receive this BCNU dose, but will be given Busulphan at a dosage of 4 mg/kg IV by 3 hour infusion (once daily for two days), finishing two days prior to the infusion of cells.
2. O6-Benzylguanine (O6BG) in combination with Temozolomide (TMZ) will be given as further cycles of chemotherapy for a maximum of 13 cycles, starting at a minimum of 21 days post infusion of gene modified cells, (provided there has been haematologic recovery and resolution of non-haematologic toxicities) as follows: Post-infusion cycle 1: 120 mg/m^2 O6BG Intravenously over 60 minutes for 5 days, and 75 mg/m^2/day TMZ orally, given 30 minutes after the end of each day's O6BG infusion. Dose escalation of the TMZ dose will occur in individual patients provided no Dose LimitingToxicity is observed in two successive cycles: as follows: Cycles 3 - 13 : Level 1 : TMZ 100 mg/m^2/day orally for 5 days, Level 2: TMZ 133 mg/M^2/day orally for 5 days, Level 3: TMZ 175mg/m^2/day orally for 5 days, Level 4: TMZ 235 mg/m^2/day orally for 5 days. Each cycle of chemotherapy will be given at a minimum of 21 days from the beginning of the previous cycle, provided there has been haematological recovery and resolution of non-haematologic toxicities.
3.Bone marrow stem cells gene-modified with a mutant drug resistance gene (MGMT) will be intravenously infused over 20 - 30 minutes, following completion of conditioning chemotherapy with O6BG and Temozolomide. Target dose minimum of 2 x 10^6 CD34+ cells.

Intervention code [1] 284782 0
Treatment: Drugs
Intervention code [2] 284783 0
Treatment: Other
Comparator / control treatment
There is no control group
Control group

Primary outcome [1] 287047 0
Safety and feasibility of the infusion of autologous Peripheral Blood Stem Cells, gene-modified with a mutant form of MGMT (designated MGMT(P140K), into paediatric patients with high risk brain tumours.
Safety will be assessed by documentation of toxicities graded according to the Common Terminology Criteria for Adverse Events (CTCAE). Feasibility will be assessed be documentation of the PBSC harvest yield, deliverable dose of gene-modified cells for infusion, measurement of engraftment of gene-modified cells.
Timepoint [1] 287047 0
Safety in relation to the chemotherapy component of the trial will be assessed following each cycle of chemotherapy given, and prior to any subsequent cycle, i.e. every 4 weeks until the end of chemotherapy treatment (up to 13 months), then monthly for the next 12 months, 3 monthly for 2 years, then 6 monthly for 2 years (5 yr timepoint) and annual assessment lifelong thereafter.
Feasability will be assessed at the time of cell infusion and then monthly until the end of chemotherapy.
Secondary outcome [1] 297268 0
To determine the:
1. efficiency of gene transfer and
2. the ability to selectively expand MGMT(P140K) expressing bone marrow cells with successive cycles of O6BG and Temozolomide treatment in paediatric patients with high risk brain tumours.
Timepoint [1] 297268 0
Gene transfer efficiency will be assessed using quantitative Polymerase-Chain-reactin (Q-PCR) of DNA extracted from gene-modified cells at the time of infusion.
Selective expansion of gene-modified cells will be assessed monthly by Q-PCR and antibody labelling of blood cells monthly prior to each chemotherapy cycle (up to 13 months)
Secondary outcome [2] 297269 0
To determine whether MGMT(P140K) expression affords the bone marrow protection from the toxic effects of chemotherapy, thus ameliorating toxicities and/or facilitating increased chemotherapy dose intensity in paediatric patients with high risk brain tumours. Tumour responses will be documented
Timepoint [2] 297269 0
Toxicities to chemotherapy will be documented following each cheomtherapy cycle (up to 13 cycles) according to CTCAE grading criteria.
Ability to dose escalate will be documented following criteria set out in the clinical protocol throughout the period during which chemotherapy is given.
Tumour responses will be documented by MRI scan prior to every second cycle of chemotherapy (ie pre-cylces 3,5,7,9,11,13) and then at the completion of chemotherapy.

Key inclusion criteria
1. Patient diagnosed with one of the following:
a) High grade glioma which has progessed or recurred following standard therapy
b) Medulloblastoma which has recurred following conventional therapy
c) Ependymoma which has recurred following maximal safe surgical resection and radiotherapy, and where maximal safe re-section and re-irradiation has been undertaken or considered not appropriate
d) Atypical teratoid/rhabdoid tumour which has recurred
e) Low grade glioma which has recurred
f) Brainstem glioma of diffuse pontine type

2. Life expectancy greater than or equal to 8 weeks
3. No severe uncontrolled infection
4. Performance status :
a) Karnofsky score > or equal to 50% (patient over 10 years old) OR
b) Lansky score > or equal to 50% (patient under/equal 10 years old)
5. Patient has adequate bone marrow function
6. Signed Informed Consent
Minimum age
1 Years
Maximum age
21 Years
Both males and females
Can healthy volunteers participate?
Key exclusion criteria
1. Uncontrolled infection
2. Malignant infiltration of the bone marrow or any other site outside the central nervous system

Study design
Purpose of the study
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
Who is / are masked / blinded?

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

Recruitment status
Date of first participant enrolment
Date of last participant enrolment
Date of last data collection
Sample size
Accrual to date
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 285182 0
Name [1] 285182 0
The Kids' Cancer Project (formerly Oncology Children's Foundation)
Address [1] 285182 0
PO Box 6400
Alexandria NSW 2015
Country [1] 285182 0
Funding source category [2] 285183 0
Name [2] 285183 0
Sporting Chance Cancer Foundation
Address [2] 285183 0
c/o Jenny Nairne
PKF Australia
Level 10, 1 Margaret St
Sydney NSW 2000
Country [2] 285183 0
Funding source category [3] 285184 0
Government body
Name [3] 285184 0
Department of Innovation, Industry Science and Research
Address [3] 285184 0
GPO Box 9839
Canberra ACT 2601
Country [3] 285184 0
Primary sponsor type
The Sydney Children's Hospital Network
The Children's Hospital at Westmead
Cnr Hawkesbury Rd and Hainsworth St
Locked Bag 4001
Westmead NSW 2145
Secondary sponsor category [1] 284050 0
Name [1] 284050 0
Address [1] 284050 0
Country [1] 284050 0

Ethics approval
Ethics application status
Ethics committee name [1] 287191 0
Sydney Children's Hospital Network Human Research Ethics Committee
Ethics committee address [1] 287191 0
Kid's Research Institute
Locked Bag 4001
Westmead NSW 2145
Ethics committee country [1] 287191 0
Date submitted for ethics approval [1] 287191 0
Approval date [1] 287191 0
Ethics approval number [1] 287191 0

Brief summary
This trial aims to test the safety and feasibility of infusing gene-modified bone marrow stem cells into paediatric patients with high risk brain tumours.
Who is it for?
Patients between the ages of 1 and 21 who have a brain tumour which has recurred, or a newly diagnosed brainstem tumour are eligible for this trial.
Trial details.
Bone marrow stem cells will be harvested from patients, and then modified with a form of a drug resistance gene called MGMT. These cells will be given back to patients after they have received chemotherapy to aid in the engraftment of the cells in the bone marrow and treat the tumour. Further cycles of chemotherapy will then be given at 4 weekly intervals and the survival and/or expansion of the gene-modified cells will be measured. If possible, the dose of chemotherapy given will be increased if the gene-modified cells successfully engraft in the patient and prove to be drug resistant to the chemotherapy.
Trial website
Trial related presentations / publications
Public notes

Principal investigator
Name 34126 0
Prof Ian Alexander
Address 34126 0
Gene Therapy Research Unit,
The Children's Hospital at Westmead
Locked Bag 4001
NSW 2145
Country 34126 0
Phone 34126 0
+ 612 9845 3071
Fax 34126 0
Email 34126 0
Contact person for public queries
Name 17373 0
Dr Dr Geoff McCowage
Address 17373 0
Senior Staff Specialist
Oncology Unit
The Children's Hospital at Westmead
Locked Bag 4001
Westmead NSW 2145
Country 17373 0
Phone 17373 0
+61 2 98452141
Fax 17373 0
Email 17373 0
Contact person for scientific queries
Name 8301 0
Prof Professor Ian Alexander
Address 8301 0
Professor in Paediatrics and Molecular Medicine
Head, Gene Therapy Research Unit
The Children's Hospital at Westmead
Locked Bag 4001
Westmead NSW 2145
Country 8301 0
Phone 8301 0
+61 2 98453071
Fax 8301 0
Email 8301 0

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