MGMT Gene Therapy and Chemotherapy for the treatment of Childhood Brain Tumours

Phase 1

Completed

Conditions: Childhood Brain Tumours
Cancer - Brain

Registration Number: ACTRN12612000535875

Lead Sponsor: The Sydney Children's Hospital Network

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 12

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

Exclusion Criteria

1. Uncontrolled infection
2. Malignant infiltration of the bone marrow or any other site outside the central nervous system

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.<br>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.[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. <br>Feasability will be assessed at the time of cell infusion and then monthly until the end of chemotherapy.]

Secondary Outcome Measures