GRAAPH-2014 treatments
| Treatment phases . | Drugs . | Doses . | Schedules . |
|---|---|---|---|
| Initial treatments | |||
| Prephase | PDN | 60 mg/m2 per day PO | Day −7 to −1 |
| MTX | 15 mg IT | Between day −7 and −4 | |
| Cycle 1 and 3 (both arms)∗ | VCR | 2 mg/day IV | Days 1, 8, 15, and 22 |
| DXM | 40 mg/day PO | Days 1-2, 8-9, 15-16, and 22-23 | |
| Nilotinib | 400 mg bid PO | Days 1 to 28 | |
| G-CSF | 5 μg/kg per day SC/IV | From day 15 to PMN recovery | |
| Cycle 2 and 4 arm A∗ | MTX (leucovorin rescue) | 1000 mg/m2 per 24 h CIV | Day 1 |
| Ara-C | 3000 mg/m2 per 12 h IV (1500 mg/m2 per 12 h IV if age ≥45 y) | Days 2-3 | |
| Nilotinib | 400 mg bid PO | Days 1 to 28 | |
| Peg-filgrastim | 6 mg SC | Day 6 | |
| Cycle 2 and 4 arm B∗ | MTX | 1000 mg/m2 per 24 h CIV | Day 1 |
| Nilotinib | 400 mg bid PO | Days 1 to 28 | |
| Peg-filgrastim | 6 mg SC | Day 6 | |
| Pre-SCT interphase (N = 2)∗ | Nilotinib | 300 mg bid PO | Days 1 to 14 |
| MTX | 25 mg/m2 per day PO | Days 1 and 8 | |
| 6-MP | 60 mg/m2 per day PO | Days 1 to 14 | |
| Postautologous and allogeneic SCT maintenance | Imatinib | 300 mg bid PO | For 24 months |
| CNS treatments | |||
| CNS prophylaxis | Triple IT† | N = 1 | Days 1, 8, and 15 of cycle 1 and day 1 of cycle 3 |
| Triple IT† | N = 1 | Day 9 of cycles 2 and 4 | |
| Triple IT† | N = 1 | Day 1 of the 2 interphase cycles | |
| If initial CNS involvement | Triple IT† | N = 12 | Between day −7 and until day 22 of cycle 2 |
| Triple IT† | N = 1 | As per prophylaxis for cycles 3 and 4 |
| Treatment phases . | Drugs . | Doses . | Schedules . |
|---|---|---|---|
| Initial treatments | |||
| Prephase | PDN | 60 mg/m2 per day PO | Day −7 to −1 |
| MTX | 15 mg IT | Between day −7 and −4 | |
| Cycle 1 and 3 (both arms)∗ | VCR | 2 mg/day IV | Days 1, 8, 15, and 22 |
| DXM | 40 mg/day PO | Days 1-2, 8-9, 15-16, and 22-23 | |
| Nilotinib | 400 mg bid PO | Days 1 to 28 | |
| G-CSF | 5 μg/kg per day SC/IV | From day 15 to PMN recovery | |
| Cycle 2 and 4 arm A∗ | MTX (leucovorin rescue) | 1000 mg/m2 per 24 h CIV | Day 1 |
| Ara-C | 3000 mg/m2 per 12 h IV (1500 mg/m2 per 12 h IV if age ≥45 y) | Days 2-3 | |
| Nilotinib | 400 mg bid PO | Days 1 to 28 | |
| Peg-filgrastim | 6 mg SC | Day 6 | |
| Cycle 2 and 4 arm B∗ | MTX | 1000 mg/m2 per 24 h CIV | Day 1 |
| Nilotinib | 400 mg bid PO | Days 1 to 28 | |
| Peg-filgrastim | 6 mg SC | Day 6 | |
| Pre-SCT interphase (N = 2)∗ | Nilotinib | 300 mg bid PO | Days 1 to 14 |
| MTX | 25 mg/m2 per day PO | Days 1 and 8 | |
| 6-MP | 60 mg/m2 per day PO | Days 1 to 14 | |
| Postautologous and allogeneic SCT maintenance | Imatinib | 300 mg bid PO | For 24 months |
| CNS treatments | |||
| CNS prophylaxis | Triple IT† | N = 1 | Days 1, 8, and 15 of cycle 1 and day 1 of cycle 3 |
| Triple IT† | N = 1 | Day 9 of cycles 2 and 4 | |
| Triple IT† | N = 1 | Day 1 of the 2 interphase cycles | |
| If initial CNS involvement | Triple IT† | N = 12 | Between day −7 and until day 22 of cycle 2 |
| Triple IT† | N = 1 | As per prophylaxis for cycles 3 and 4 |
Ara-C, cytarabine; CIV, continuous IV; CNS, central nervous system; DXM, dexamethasone; G-CSF, granulocyte colony-stimulating factor; IT, intrathecal; IV, intravenous; 6-MP, 6-mercaptopurine; MTX, methotrexate; PDN, prednisone; PMN, neutrophils; PO, per os (by mouth); SC, subcutaneously; VCR, vincristine.
Cycles 2, 3, and 4 and interphase start at day 29 of prior cycle.
Triple IT consisted of 15 mg MTX, 40 mg Ara-C, and 40 mg PDN IT.