Study: NCT00795132

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Fludarabine
Description: Administration and Dosage: Fludarabine will be administered at a dose of 30 mg/m2 in 100 ml of D5W intravenously over one hour on each of six consecutive days -10 through -5 for unrelated grafts or d-7 through d-2 for related grafts. Fludarabine is a fluorinated nucleotide analog of the antiviral agent vidarabine, 9-beta-D-arabinofuranosyladenine. Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. The half-life of 2-fluoro-ara-A is approximately 10 hours. The mean total plasma clearance is 8.9 L/hr/m2 and the mean volume of distribution is 98 L/m2. Approximately 23% is excreted unchanged. This metabolite appears to act by inhibiting DNA polymerase alpha, ribonucleotide reductase and DNA primase, thus inhibiting DNA synthesis.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Cyclosporine
Description: Cyclosporine is a potent immunosuppressive agent that in animals prolongs survival of allogeneic transplants involving skin, kidney, liver, heart, pancreas, bone marrow, small intestine, and lung. The effectiveness of cyclosporine results from specific and reversible inhibition of immunocompetent lymphocytes in the G 0 - and G~1 -phase of the cell cycle. Administration and Dosage: Cyclosporin start on day -3 initially at a dose of 2.5mg/kg IV q12 hours or 3mg/kg/dose (neoral equivalent) PO q12 hours targeting suggested troughs of 250 to 350 ng/ml. Continuous infusion cyclosporin may be allowed per institutional preference. 3x daily dosing may be used for younger children to achieve therapeutic levels. PBMTC Protocol #ONC0313 19 Continuous infusion cyclosporin may be allowed per institutional preference.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Cyclosporine
Description: Cyclosporine is a potent immunosuppressive agent that in animals prolongs survival of allogeneic transplants involving skin, kidney, liver, heart, pancreas, bone marrow, small intestine, and lung. The effectiveness of cyclosporine results from specific and reversible inhibition of immunocompetent lymphocytes in the G 0 - and G~1 -phase of the cell cycle. Administration and Dosage: Cyclosporin start on day -3 initially at a dose of 2.5mg/kg IV q12 hours or 3mg/kg/dose (neoral equivalent) PO q12 hours targeting suggested troughs of 250 to 350 ng/ml. Continuous infusion cyclosporin may be allowed per institutional preference. 3x daily dosing may be used for younger children to achieve therapeutic levels. PBMTC Protocol #ONC0313 19 Continuous infusion cyclosporin may be allowed per institutional preference.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Cyclosporine
Description: Cyclosporine is a potent immunosuppressive agent that in animals prolongs survival of allogeneic transplants involving skin, kidney, liver, heart, pancreas, bone marrow, small intestine, and lung. The effectiveness of cyclosporine results from specific and reversible inhibition of immunocompetent lymphocytes in the G 0 - and G~1 -phase of the cell cycle. Administration and Dosage: Cyclosporin start on day -3 initially at a dose of 2.5mg/kg IV q12 hours or 3mg/kg/dose (neoral equivalent) PO q12 hours targeting suggested troughs of 250 to 350 ng/ml. Continuous infusion cyclosporin may be allowed per institutional preference. 3x daily dosing may be used for younger children to achieve therapeutic levels. PBMTC Protocol #ONC0313 19 Continuous infusion cyclosporin may be allowed per institutional preference.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Mycophenolate mofetil
Description: MMF is a potent, selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA. Administration and Dosage: Initial dosage will be IV or PO with switch to PO when tolerated. Starting doses will be 15 mg/kg/day bid (total dose 30mg/kg/d, IV same as PO dose) beginning day 0 with the first dose given approximately 4-6 hours after the stem cell infusion. This dose will stop on day +30 for patients receiving matched sibling BM/PBSC and UCB grafts, but will continue until day +40 and then taper at approximately 11%/wk over 8 weeks until patients are off at day +96.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Mycophenolate mofetil
Description: MMF is a potent, selective, uncompetitive, and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), and therefore inhibits the de novo pathway of guanosine nucleotide synthesis without incorporation into DNA. Administration and Dosage: Initial dosage will be IV or PO with switch to PO when tolerated. Starting doses will be 15 mg/kg/day bid (total dose 30mg/kg/d, IV same as PO dose) beginning day 0 with the first dose given approximately 4-6 hours after the stem cell infusion. This dose will stop on day +30 for patients receiving matched sibling BM/PBSC and UCB grafts, but will continue until day +40 and then taper at approximately 11%/wk over 8 weeks until patients are off at day +96.