GRAAPH-2005 treatments
| Treatment phases . | Drugs . | Doses . | Schedules . |
|---|---|---|---|
| Initial treatments | |||
| Prephase | PDN | 60 mg/m2/d po | Day −7 to day −1 |
| MTX | 15 mg IT | Between day −7 and day −4 | |
| Cycle 1 arm A | VCR | 2 mg/d IV | Days 1, 8, 15, and 22 |
| DXM | 40 mg/d po | Days 1-2, 8-9, 15-16, and 22-23 | |
| Imatinib | 400 mg bid po | Days 1-28 | |
| Filgrastim | 5 μg/kg/d sc/IV | From day 15 to PMN recovery | |
| Cycle 1 arm B | VCR | 2 mg/d IV | Day 4 and day 11 |
| DXM | 40 mg/d po | Days 1-4 and 11-14 | |
| DXR | 50 mg/m2/d CIV | Day 4 | |
| CPM | 300 mg/m2/12 h IV | Day 1-3 | |
| Imatinib | 400 mg bid po | Day 1-14 | |
| Filgrastim or pegfilgrastim | 5 μg/kg/d sc/IV (filgrastim) or 6 mg sc (pegfilgrastim) | From day 15 to PMN recovery (filgrastim) or day 6 (pegfilgrastim) | |
| Cycle 2 (both arms) | MTX | 1000 mg/m2/d CIV | Day 1 |
| Ara-C | 3000 mg/m2/12 h IV | Days 2-3 | |
| Imatinib | 400 mg bid po | Days 1-14 | |
| Filgrastim or pegfilgrastim | 5 μg/kg/d sc/IV (filgrastim) or 6 mg sc (pegfilgrastim) | From day 9 to PMN recovery (filgrastim) or day 6 (pegfilgrastim) | |
| Pre-SCT interphase (n = 2) | MTX | 25 mg/m2/d po | Days 1 and 8 |
| 6-MP | 60 mg/m2/d po | Days 1-14 | |
| Imatinib | 300 mg bid po | Days 1-14 | |
| Further treatments for non-SCT patients | |||
| Cycles 3, 5, and 7 | Identical to cycle 1 arm B, with reduced 300 mg imatinib bid from day 1 to day 14 | ||
| Cycles 4, 6, and 8 | Identical to cycle 2, with reduced 300 mg imatinib bid from day 1 to day 14 | ||
| Monthly maintenance cycles | Replaced at month 6 by a cycle 9 (like cycles 3, 5 and 7) and at month 12 by a cycle 10 (like cycles 4, 6, and 8) | ||
| PDN | 200 mg/d po | Days 1-5, months 1-12 | |
| VCR | 2 mg/d IV | Day 1, months 1-12 | |
| Imatinib | 300 mg bid po | Months 1-24 | |
| Post–autologous SCT maintenance | |||
| Months 1, 3, 5... to 23 | Imatinib | 300 mg bid po | For 1 mo |
| Months 2, 4, 6... to 24 | MTX | 25 mg/m2/wk po | For 1 mo |
| 6-MP | 60 mg/m2/d po | For 1 mo | |
| CNS treatments | |||
| CNS prophylaxis | Triple IT* | n = 1 | Days 1, 8, and 15 of cycle 1 |
| Triple IT | n = 1 | Day 9 of cycle 2 | |
| Triple IT | n = 1 | Day 1 of the 2 interphase cycles | |
| If initial CNS involvement | Triple IT | n = 8 | Between day −7 and day 21 of cycle 1 |
| Triple IT | n = 1 per wk thereafter | For a total of 12 ITs | |
| Cranial irradiation | 15 Gy before SCT or 24 Gy after cycle 8 in non-SCT patients | ||
| Imatinib | 300 mg bid po | During cranial irradiation | |
| Treatment phases . | Drugs . | Doses . | Schedules . |
|---|---|---|---|
| Initial treatments | |||
| Prephase | PDN | 60 mg/m2/d po | Day −7 to day −1 |
| MTX | 15 mg IT | Between day −7 and day −4 | |
| Cycle 1 arm A | VCR | 2 mg/d IV | Days 1, 8, 15, and 22 |
| DXM | 40 mg/d po | Days 1-2, 8-9, 15-16, and 22-23 | |
| Imatinib | 400 mg bid po | Days 1-28 | |
| Filgrastim | 5 μg/kg/d sc/IV | From day 15 to PMN recovery | |
| Cycle 1 arm B | VCR | 2 mg/d IV | Day 4 and day 11 |
| DXM | 40 mg/d po | Days 1-4 and 11-14 | |
| DXR | 50 mg/m2/d CIV | Day 4 | |
| CPM | 300 mg/m2/12 h IV | Day 1-3 | |
| Imatinib | 400 mg bid po | Day 1-14 | |
| Filgrastim or pegfilgrastim | 5 μg/kg/d sc/IV (filgrastim) or 6 mg sc (pegfilgrastim) | From day 15 to PMN recovery (filgrastim) or day 6 (pegfilgrastim) | |
| Cycle 2 (both arms) | MTX | 1000 mg/m2/d CIV | Day 1 |
| Ara-C | 3000 mg/m2/12 h IV | Days 2-3 | |
| Imatinib | 400 mg bid po | Days 1-14 | |
| Filgrastim or pegfilgrastim | 5 μg/kg/d sc/IV (filgrastim) or 6 mg sc (pegfilgrastim) | From day 9 to PMN recovery (filgrastim) or day 6 (pegfilgrastim) | |
| Pre-SCT interphase (n = 2) | MTX | 25 mg/m2/d po | Days 1 and 8 |
| 6-MP | 60 mg/m2/d po | Days 1-14 | |
| Imatinib | 300 mg bid po | Days 1-14 | |
| Further treatments for non-SCT patients | |||
| Cycles 3, 5, and 7 | Identical to cycle 1 arm B, with reduced 300 mg imatinib bid from day 1 to day 14 | ||
| Cycles 4, 6, and 8 | Identical to cycle 2, with reduced 300 mg imatinib bid from day 1 to day 14 | ||
| Monthly maintenance cycles | Replaced at month 6 by a cycle 9 (like cycles 3, 5 and 7) and at month 12 by a cycle 10 (like cycles 4, 6, and 8) | ||
| PDN | 200 mg/d po | Days 1-5, months 1-12 | |
| VCR | 2 mg/d IV | Day 1, months 1-12 | |
| Imatinib | 300 mg bid po | Months 1-24 | |
| Post–autologous SCT maintenance | |||
| Months 1, 3, 5... to 23 | Imatinib | 300 mg bid po | For 1 mo |
| Months 2, 4, 6... to 24 | MTX | 25 mg/m2/wk po | For 1 mo |
| 6-MP | 60 mg/m2/d po | For 1 mo | |
| CNS treatments | |||
| CNS prophylaxis | Triple IT* | n = 1 | Days 1, 8, and 15 of cycle 1 |
| Triple IT | n = 1 | Day 9 of cycle 2 | |
| Triple IT | n = 1 | Day 1 of the 2 interphase cycles | |
| If initial CNS involvement | Triple IT | n = 8 | Between day −7 and day 21 of cycle 1 |
| Triple IT | n = 1 per wk thereafter | For a total of 12 ITs | |
| Cranial irradiation | 15 Gy before SCT or 24 Gy after cycle 8 in non-SCT patients | ||
| Imatinib | 300 mg bid po | During cranial irradiation | |
Ara-C, cytarabine; bid, twice daily; CIV, continuous IV; CNS, central nervous system; CPM, cyclophosphamide; DXM, dexamethasone; DXR, doxorubicin; IT, intrathecal; 6-MP, 6-mercaptopurine; MTX, methotrexate; PDN, prednisone; PMN, polymorphonuclear neutrophil; po, by mouth; sc, subcutaneously; VCR, vincristine.
Triple IT consisted of 15 mg MTX, 40 mg Ara-C, and 40 mg PDN.