None listed
Conditions
Brief summary
Most children with leukaemia are cured, but those with the worst forms do less well. This trial is testing new ways of combining the most effective drugs, and adding a tranplant for children with the worst forms of leukaemia and a suitable donor. This tiral will determine if these new approaches could improve cure rates, and if they could be used more widely.
Interventions
This study involves the administration of Chemotherapy regimes for duration of 2 years. Control group (standard risk and medium risk patients) receives standard chemotherapy regimen for acute lymphoblastic leukaemia in children. Intervention group (high risk and very high risk patients) receives standard chemotherapy regimen similar to the control group plus 2 courses of three different chemotherapy regimes.
Standard chemotherapy regime (given in the following order):
Protocol 1 Days 1-33:
Pr
This study involves the administration of Chemotherapy regimes for duration of 2 years. Control group (standard risk and medium risk patients) receives standard chemotherapy regimen for acute lymphoblastic leukaemia in children. Intervention group (high risk and very high risk patients) receives standard chemotherapy regimen similar to the control group plus 2 courses of three different chemotherapy regimes. Standard chemotherapy regime (given in the following order): Protocol 1 Days 1-33: Prednisolone 60mg/m2 intravenous(IV) or per os(PO) ie through the mouth Vincristine 1.5mg/m2 IV L'Asparaginase 5000IU/m2 intramuscular injection (IMI) Daunorubicin 30mg/m2 IV intrathecal (IT) Methotrexate(MTX) Age related dose 1-2years 8mg 2-3 years 10mg >3years 12mg Protocol 1 Days 36-79: Cytarabine 75mg/m2 IV or subcutaneous (SC) Mercaptopurine 60mg/m2 PO Cyclophosphamide 1000mg/m2 IV IT MTX age related doses as above Protocol M Days 1-57: Mercaptopurine 25mg/m2 PO Methotrexate 5000mg/m2 IV 4500mg/m2 IV IT Methotrexate age related doses as above Folinic Acid 15mg/m2 IV Protocol II Days 1-36: Dexamethasone 10mg/m2 PO Vincristine 1.5mg/m2 IV L-Asparaginase 10 000 Iu /m2 IMI Doxorubicin 30mg/m2 IV IT Methotrexate age related dose as above Protocol II Days 36-49: Cytarabine 75mg/m2 IV or SC Thioguanine 60mg/m2 PO IT Methotrexate age related dose as above Cyclophosphamide 1000mg/m2 IV Maintenance Therapy: Required until a total of 104 weeks of therapy has been completed Mercaptopurine 50mg/m2/day PO Methotrexate 20mg/m2/week PO Additional chemotherapy regimes (intervention): Interventional group will receive protocol 1 (as in the standard chemotherapy regime) and then either 1 or 2 courses of three different chemotherapy regimes (described below) depending on risk. Each High Risk block should be given at five week intervals and ideally no break between courses. The patients will then receive protocol II and Maintenance therapy (as in the standard chemotherapy regime). Patients classified as ‘very high risk’ may or may not receive a stem cell transplant depending on if there is a suitable donor. If they do receive a stem cell transplant then these patients do not receive the second chemotherapy course. High Risk 1 Course 1 6-Mercaptopurine 25mg/m2 PO Methotrexate 5g/m2 IV Vincristine 1.5mg/m2 IV L'Asparaginase 10 000 IU/m2 IMI Etoposide 350mg/m2 IV Cyclophsphamide 1200mg/m2 IV IT Methotrexate Age related dose as above IT Cytaraine Age related dose 1-2 years 20mg 2-3 years 26mg >3 years 30mg IT Hydrocortisone Age related dose 1-2years 30mg 2-3years 40mg >3years 50mg granulocyte colony stimulating factor(GCSF) 10mcg/kg/day SC High Risk 2 Course 1 Methotrexate 5g/m2 IV Vincristine 1.5mg/m2/day IV L'Asparaginase 10 000 IU/m2/day IMi Cytarabine 2000mg/m2 IV Mitoxantrone 7mg/day IV IT Methotrexate Age related dose as above IT Cytarabine Age related dose as above IT Hydrocortisone Age related doses as above GCSF 5mcg/kg/day SC High Risk 3 Course 1 Methotrexate 5g/m2 IV Idarubicin 8mg/m2/day IV Cytarabine 2000mg/m2/day IV Fludarabine 30mg/m2/day IV IT Methotrexate Age related dose as above IT Cytarabine Age related dose as above IT Hydrocortisone Age related dose as above GCSF 5mcg/kg/day SC High High Risk 1 Course 2 Methotrexate 5g/m2 IV Vincristine 1.5mg/m2 IV bolus L'Asparaginase 10 000 IU/day IMI Etoposide 350mg/m2/day IV Cyclophosphamide 1200mg/m2/day IV IT Methotrexate Age related dose as above IT Cytarabine Age related dose as above IT Hydrocortisone Age related dose as above GCSF 5mcg/kg/day SC High Risk 2 Course 2 Methotrexate 5g/m2 IV Vincristine 1.5mg/m2/day IV L'Asparaginase 10 000 IU /m2/day IMI Cytarabine 2000mg/m2 IV Mitoxantrone 7mg/m2/day IV IT Methotrexate Age related dose as above IT Cytarabine Age related dose as above IT Hydrocortisone Age related dose as above GCSF 5mcg/kg/day High Risk 3 Course 2 Methotrexate 5g/m2 IV Cytarabine 2000mg/m2/day IV Fludarabine 30mg/m2/day IV IT Methotrexate Age related dose as above IT Cytarabine Age related dose as above IT Hydrocortisone Age related dose as above GCSF 5mcg/kg/day SC
Sponsors
ANZCHOG
Study design
Allocation
Non-randomised trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
1 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1) All newly diagnosed children with ALL aged between 1 and 17 years of age (inclusive). 2) Written informed consent obtained within 14 days of commencement of systemic therapy since initial induction therapy is a standard 5 drug regimen 3) Patients with any of the following characteristics are also eligible: - B or T lineage immunophenotype - co-expression of myeloid and lymphoid antigens - t(9;22), t(4;11) - Down syndrome - central nervous system leukaemia, extramedullary disease or bulky mass disease - Day 15 bone marrow showing >5% blasts (M2 of M3)
Exclusion criteria
1) Age less than 1 year, or greater than or equal to 18 years 2) ALL occurring as a second malignancy 3) Patients with biphenotypic or bilineage leukaemia 4) Patients who develop a documented switch in the lineage of the leukaemia (after commencing Protocol I) 5) Mature B cell ALL with t(8;14), t(2;8), t(8;22) 6) Previously treated patients: - systemic corticosteroids administered for any reason at a dose equivalent to or greater than 1mg/kg/day. - Prednisolone for more than 72 hours within 4 weeks of diagnosis
Outcome results
None listed