EORTC-CLG treatment protocol for AR (AR1 and AR2) patients
| Drug . | Dose . | Days of administration . |
|---|---|---|
| Induction: protocol IA | ||
| Methotrexate (IT)* | 1 | |
| According to randomization | ||
| PRED (PO) | 60 mg/m2 | 1-7 (prephase) |
| DEX (PO) | 6 mg/m2 | 1-7 (prephase) |
| According to randomization | ||
| PRED (PO) | 60 mg/m2 | 8-28, tapered over 9 d |
| DEX (PO) | 6 mg/m2 | 8-28, tapered over 9 d |
| AR1 | ||
| Vincristine (IV) | 1.5 mg/m2 (max 2 mg) | 8, 15, 22, 29 |
| Daunorubicin (IV) | 30 mg/m2 | 8, 15, 22, 29 |
| Triple chemotherapy (IT)* | 8, 22 | |
| Escherichia coli asparaginase | 10 000 IU/m2 | 12, 15, 18, 22, 25, 29, 32, 35 |
| AR2 | ||
| Cyclophosphamide | 1000 mg/m2 | 9 |
| Methotrexate (24 h)† | 5 g/m2 | 8 |
| Triple chemotherapy (IT)* | 9, 22 | |
| Vincristine (IV) | 1.5 mg/m2 (max 2 mg) | 8, 15, 22, 29 |
| Daunorubicin (IV) | 40 mg/m2 | 15, 22, 29 |
| E coli asparaginase | 10 000 IU/m2 | 12, 15, 18, 22, 25, 29,3 2, 35 |
| Consolidation: protocol IB | ||
| Cyclophosphamide (IV) | 1000 mg/m2 | 36, 63 |
| Cytarabine (IV) | 75 mg/m2 | 38-41, 45-48, 52-55, 59-62 |
| Triple chemotherapy (IT)* | 38, 52 | |
| 6-Mercaptopurine (PO) | 60 mg/m2 | 36-63 |
| According to randomization | ||
| No asparaginase | ||
| E coli asparaginase | 5000 IU/m2 | 38, 41, 45, 48, 52, 55, 59, 62 |
| Interval therapy | ||
| 6-Mercaptopurine (PO) | 25 mg/m2 | 1-56 |
| Methotrexate (24 h)† | 5000 mg/m2 | 8, 22, 36, 50 |
| Triple chemotherapy (IT)* | 9, 23, 37, 51 | |
| Late intensification: protocol II | ||
| DEX (PO) | 6 mg/m2 | 1-21, taper over 9 d |
| Vincristine (IV) | 1.5 mg/m2 (max 2 mg) | 8, 15, 22, 29 |
| Doxorubicin (IV) | 30 mg/m2 | 8, 15, 22, 29 |
| Triple chemotherapy (IT)* | 38 | |
| Cyclophosphamide (IV) | 1000 mg/m2 | 36 |
| Cytarabine (IV) | 75 mg/m2 | 38-41, 45-48 |
| 6-Thioguanine (PO) | 60 mg/m2 | 36-49 |
| According to randomization | ||
| E coli asparaginase | 10 000 IU/m2 | 8, 11, 15, 18 |
| E coli asparaginase | 10 000 IU/m2 | 8, 11, 15, 18 |
| 5000 IU/m2 | 22, 25, 29, 32 | |
| Maintenance (74 wk) | ||
| AR1 | ||
| 6-Mercaptopurine (PO) | 50 mg/m2 | Daily |
| Methotrexate (PO) | 20 mg/m2 | Weekly |
| Triple chemotherapy (IT)* | Every 70 d, starting D22, 6 times | |
| According to randomization | ||
| No pulses | ||
| PRED (PO)‡ | 60 mg/m2 | Every 70 d, for 7 d, starting D57-63, 6 times |
| DEX (PO)‡ | 6 mg/m2 | Every 70 d, for 7 d, starting D57-63, 6 times |
| Vincristine | 1.5 mg/m2 (max 2 mg) | Every 70 d, on D57 and D63, 6 times |
| AR2 | ||
| 6-Mercaptopurine (PO) | 50 mg/m2 | Daily |
| Methotrexate (PO) | 20 mg/m2 | Weekly |
| Methotrexate (24 h)† | 5000 mg/m2 | Every 70 d, starting D22, 6 times |
| Triple chemotherapy (IT)* | Every 70 d, starting D23, 6 times | |
| E coli asparaginase | 25 000 IU/m2 | Every 70 d, starting D23, 6 times |
| According to randomization | ||
| No pulses | ||
| PRED (PO)‡ | 60 mg/m2 | Every 70 d, for 7 d starting D57-63, 6 times |
| DEX (PO)‡ | 6 mg/m2 | Every 70 d, for 7 d, starting D57-63, 6 times |
| Vincristine (IV) | 1.5 mg/m2 (max 2 mg) | Every 70 d, on D57 and D63, 6 times |
| Drug . | Dose . | Days of administration . |
|---|---|---|
| Induction: protocol IA | ||
| Methotrexate (IT)* | 1 | |
| According to randomization | ||
| PRED (PO) | 60 mg/m2 | 1-7 (prephase) |
| DEX (PO) | 6 mg/m2 | 1-7 (prephase) |
| According to randomization | ||
| PRED (PO) | 60 mg/m2 | 8-28, tapered over 9 d |
| DEX (PO) | 6 mg/m2 | 8-28, tapered over 9 d |
| AR1 | ||
| Vincristine (IV) | 1.5 mg/m2 (max 2 mg) | 8, 15, 22, 29 |
| Daunorubicin (IV) | 30 mg/m2 | 8, 15, 22, 29 |
| Triple chemotherapy (IT)* | 8, 22 | |
| Escherichia coli asparaginase | 10 000 IU/m2 | 12, 15, 18, 22, 25, 29, 32, 35 |
| AR2 | ||
| Cyclophosphamide | 1000 mg/m2 | 9 |
| Methotrexate (24 h)† | 5 g/m2 | 8 |
| Triple chemotherapy (IT)* | 9, 22 | |
| Vincristine (IV) | 1.5 mg/m2 (max 2 mg) | 8, 15, 22, 29 |
| Daunorubicin (IV) | 40 mg/m2 | 15, 22, 29 |
| E coli asparaginase | 10 000 IU/m2 | 12, 15, 18, 22, 25, 29,3 2, 35 |
| Consolidation: protocol IB | ||
| Cyclophosphamide (IV) | 1000 mg/m2 | 36, 63 |
| Cytarabine (IV) | 75 mg/m2 | 38-41, 45-48, 52-55, 59-62 |
| Triple chemotherapy (IT)* | 38, 52 | |
| 6-Mercaptopurine (PO) | 60 mg/m2 | 36-63 |
| According to randomization | ||
| No asparaginase | ||
| E coli asparaginase | 5000 IU/m2 | 38, 41, 45, 48, 52, 55, 59, 62 |
| Interval therapy | ||
| 6-Mercaptopurine (PO) | 25 mg/m2 | 1-56 |
| Methotrexate (24 h)† | 5000 mg/m2 | 8, 22, 36, 50 |
| Triple chemotherapy (IT)* | 9, 23, 37, 51 | |
| Late intensification: protocol II | ||
| DEX (PO) | 6 mg/m2 | 1-21, taper over 9 d |
| Vincristine (IV) | 1.5 mg/m2 (max 2 mg) | 8, 15, 22, 29 |
| Doxorubicin (IV) | 30 mg/m2 | 8, 15, 22, 29 |
| Triple chemotherapy (IT)* | 38 | |
| Cyclophosphamide (IV) | 1000 mg/m2 | 36 |
| Cytarabine (IV) | 75 mg/m2 | 38-41, 45-48 |
| 6-Thioguanine (PO) | 60 mg/m2 | 36-49 |
| According to randomization | ||
| E coli asparaginase | 10 000 IU/m2 | 8, 11, 15, 18 |
| E coli asparaginase | 10 000 IU/m2 | 8, 11, 15, 18 |
| 5000 IU/m2 | 22, 25, 29, 32 | |
| Maintenance (74 wk) | ||
| AR1 | ||
| 6-Mercaptopurine (PO) | 50 mg/m2 | Daily |
| Methotrexate (PO) | 20 mg/m2 | Weekly |
| Triple chemotherapy (IT)* | Every 70 d, starting D22, 6 times | |
| According to randomization | ||
| No pulses | ||
| PRED (PO)‡ | 60 mg/m2 | Every 70 d, for 7 d, starting D57-63, 6 times |
| DEX (PO)‡ | 6 mg/m2 | Every 70 d, for 7 d, starting D57-63, 6 times |
| Vincristine | 1.5 mg/m2 (max 2 mg) | Every 70 d, on D57 and D63, 6 times |
| AR2 | ||
| 6-Mercaptopurine (PO) | 50 mg/m2 | Daily |
| Methotrexate (PO) | 20 mg/m2 | Weekly |
| Methotrexate (24 h)† | 5000 mg/m2 | Every 70 d, starting D22, 6 times |
| Triple chemotherapy (IT)* | Every 70 d, starting D23, 6 times | |
| E coli asparaginase | 25 000 IU/m2 | Every 70 d, starting D23, 6 times |
| According to randomization | ||
| No pulses | ||
| PRED (PO)‡ | 60 mg/m2 | Every 70 d, for 7 d starting D57-63, 6 times |
| DEX (PO)‡ | 6 mg/m2 | Every 70 d, for 7 d, starting D57-63, 6 times |
| Vincristine (IV) | 1.5 mg/m2 (max 2 mg) | Every 70 d, on D57 and D63, 6 times |
IT indicates intrathecally; PO, orally; PRED, prednisolone; DEX, dexamethasone; IV, intravenously; and D/d, day.
Methotrexate: younger than 1 year, 6 mg; 1 year, 8 mg; 2 years, 10 mg; 3 years and older, 12 mg. Cytarabine: younger than 1 year, 15 mg; 1 year, 20 mg; 2 years 25 mg; 3 years and older, 30 mg. Hydrocortisone: younger than 1 year, 7.5 mg; 1 year, 10 mg; 2 years, 12.5 mg; 3 years and older, 15 mg.
Leucovorin rescue 12 mg/m2 every 6 hours starts at hour 36.
Same corticosteroid as initial randomization (protocol IA).