Table I:
Treatment Plan
| Study Phase | Dosing |
|---|---|
| Block 1 (VPLD) 28 days; response at Day 28–36 | |
| CNS 1 or 2: IT- AraC/ IT- MTX* | Day 1/ Day 15 and 29 |
| CNS3: IT-AraC/IT-MTX + HC + AraC (ITT)* | Day 1/Days 8, 15, 22 and 29 |
| Vincristine 1.5 mg/m2 (max 2 mg) IV | Days 1, 8, 15, and 22 |
| Doxorubicin (60 mg/m2) IV | Day 1 |
| Prednisone (40 mg/m2/day PO divided BID)** | Days 1–28 |
| Bortezomib (1.3 mg/m2) IV | Days 1, 4, 8, and 11 |
| PEG-asparaginase (2500 units/m2) IM | Days 2, 8, 15, and 22 |
| Block 2: 28 days; response at Day 28–36 | |
| CNS1: IT MTX/ CNS3 ITT | Days 1 and 22 |
| Etoposide (100 mg/m2) IV | Days 1–5 |
| Cyclophosphamide (440 mg/m2) IV | Days 1–5 |
| Bortezomib (1.3 mg/m2 ) IV | Days 1, 4, and 8 |
| Methotrexate (5 000 mg/m2) IV | Day 22 |
| Block 3: 28 days; response assessed at Day 28 | |
| Cytarabine (3 000 mg/m2/dose) IV BID | Days 1, 2, 8 and 9 |
| E-coli asparaginase (6 000 units/m2) IM *** | Days 2 and 9 |
IT therapy followed age-based dosing. Day 1: Cytarabine 30 mg (age 1–2 years), 50 mg (age 2–3 years) or 70 mg (>3 years). Subsequent days for CNS-negative: IT MTX: 8 mg (ages 1–2 years), 10 mg (2–3 years), 12 mg (3–9 years) or 15 mg (>9 years). Subsequent days for CNS-positive: MTX: 8 mg, HC: 8 mg, AraC: 16 mg (1–2 y), MTX: 10 mg, HC: 10 mg, AraC: 20 mg (2–3 years); MTX: 12 mg, HC: 12 mg, AraC: 24 mg (3–9 years) or MTX: 15 mg, HC: 15 mg, AraC: 30 mg (>9 years).
Methylprednisolone IV could be substituted for prednisone PO.
Alternative asparaginase regimen: PEG-asparaginase 2500 units/m2 IM on Day 2.
AraC: cytarabine; BID: twice a day; CNS: central nervous system; HC: hydrocortisone; IM: intramuscularly; IT: intrathecal; ITT: intention-to-treat; IV: intravenously; PO: orally; VPLD vincristine, prednisone, pegylated asparaginase and doxorubicin