None listed
Conditions
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.
Interventions
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 chemothera
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.
Sponsors
The Sydney Children's Hospital Network
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
1 Years to 21 Years
Healthy volunteers
No
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
Outcome results
None listed