Chemotherapy Regimens

Acute Lymphocytic Leukemia

CALGB 8811

(6 modifications)
Induction, patients <60 years of age (4-week cycle):
Cyclophosphamide: IV: 1200 mg/m2 day 1 [total dose/cycle = 1200 mg/m2]
Daunorubicin: IV: 45 mg/m2/dose days 1, 2, and 3 [total dose/cycle = 135 mg/m2]
Vincristine: IV: 2 mg/dose days 1, 8, 15, and 22 [total dose/cycle = 8 mg]
Prednisone: Oral: 60 mg/m2/dose days 1 to 21 [total dose/cycle = 1260 mg/m2]
Asparaginase (E. coli): SubQ: 6000 units/m2/dose days 5, 8, 11, 15, 18, and 22 [total dose/cycle = 36,000 units/m2]

Induction, patients ≥60 years of age (4-week cycle):
Cyclophosphamide: IV: 800 mg/m2 day 1 [total dose/cycle = 800 mg/m2]
Daunorubicin: IV: 30 mg/m2/dose days 1, 2, and 3 [total dose/cycle = 90 mg/m2]
Vincristine: IV: 2 mg/dose days 1, 8, 15, and 22 [total dose/cycle = 8 mg]
Prednisone: Oral: 60 mg/m2/dose days 1 to 7 [total dose/cycle = 420 mg/m2]
Asparaginase (E. coli): SubQ: 6000 units/m2/dose days 5, 8, 11, 15, 18, and 22 [total dose/cycle = 36,000 units/m2]

Early intensification (4-week cycle; repeat cycle once):
Methotrexate: Intrathecal: 15 mg/dose day 1 [total dose/cycle = 15 mg]
Cyclophosphamide: IV: 1000 mg/m2 day 1 [total dose/cycle = 1000 mg/m2]
Mercaptopurine: Oral: 60 mg/m2/dose days 1 to 14 [total dose/cycle = 840 mg/m2]
Cytarabine: SubQ: 75 mg/m2/dose days 1 to 4 and 8 to 11 [total dose/cycle = 600 mg/m2]
Vincristine: IV: 2 mg/dose days 15 and 22 [total dose/cycle = 4 mg]
Asparaginase (E. coli): SubQ: 6000 units/m2/dose days 15, 18, 22, and 25 [total dose/cycle = 24,000 units/m2]

CNS prophylaxis/interim maintenance (12-week duration; with cranial irradiation days 1 to 12):
Methotrexate: Intrathecal: 15 mg/dose days 1, 8, 15, 22, and 29 [total dose/cycle = 75 mg]
Mercaptopurine: Oral: 60 mg/m2/dose days 1 to 70 [total dose/cycle = 4200 mg/m2]
Methotrexate: Oral: 20 mg/m2/dose days 36, 43, 50, 57, and 64 [total dose/cycle = 100 mg/m2]

Late intensification (8-week cycle):
Doxorubicin: IV: 30 mg/m2/dose days 1, 8, and 15 [total dose/cycle = 90 mg/m2]
Vincristine: IV: 2 mg/dose days 1, 8, and 15 [total dose/cycle = 6 mg]
Dexamethasone: Oral: 10 mg/m2/dose days 1 to 14 [total dose/cycle = 140 mg/m2]
Cyclophosphamide: IV: 1000 mg/m2 day 29 [total dose/cycle = 1000 mg/m2]
Thioguanine: Oral: 60 mg/m2/dose days 29 to 42 [total dose/cycle = 840 mg/m2]
Cytarabine: SubQ: 75 mg/m2/dose days 29 to 32 and 36 to 39 [total dose/cycle = 600 mg/m2]

Maintenance (continue until 24 months from diagnosis):
Vincristine: IV: 2 mg/dose day 1 every 4 weeks [total dose/4 weeks = 2 mg]
Prednisone: Oral: 60 mg/m2/dose days 1 to 5 every 4 weeks [total dose/4 weeks = 300 mg/m2]
Methotrexate: Oral: 20 mg/m2/dose days 1, 8, 15, and 22 [total dose/phase = 80 mg/m2]
Mercaptopurine: Oral: 60 mg/m2/dose days 1 to 28 [total dose/phase = 1680 mg/m2]

CALGB 9111

(6 modifications)
Induction, patients <60 years of age (4-week cycle):
Cyclophosphamide: IV: 1200 mg/m2 day 1[total dose/cycle = 1200 mg/m2]
Daunorubicin: IV: 45 mg/m2/dose days 1, 2, and 3[total dose/cycle = 135 mg/m2]
Vincristine: IV: 2 mg/dose days 1, 8, 15, and 22[total dose/cycle = 8 mg]
Prednisone: Oral: 60 mg/m2/dose days 1 to 21[total dose/cycle = 1260 mg/m2]
Asparaginase (E. coli): SubQ, IM: 6000 units/m2/dose days 5, 8, 11, 15, 18, and 22[total dose/cycle = 36,000 units/m2]
Filgrastim: SubQ: 5 mcg/kg/day starting day 4; continue for at least 7 days and until ANC ≥1000/mm3 on two draws, 24 hours apart

Induction, patients ≥60 years of age (4-week cycle):
Cyclophosphamide: IV: 800 mg/m2 day 1[total dose/cycle = 800 mg/m2]
Daunorubicin: IV: 30 mg/m2/dose days 1, 2, and 3[total dose/cycle = 90 mg/m2]
Vincristine: IV: 2 mg/dose days 1, 8, 15, and 22[total dose/cycle = 8 mg]
Prednisone: Oral: 60 mg/m2/dose days 1 to 7[total dose/cycle = 420 mg/m2]
Asparaginase (E. coli): SubQ, IM: 6000 units/m2/dose days 5, 8, 11, 15, 18, and 22[total dose/cycle = 36,000 units/m2]
Filgrastim: SubQ: 5 mcg/kg/day starting day 4; continue for at least 7 days and until ANC ≥1000/mm3 on two draws, 24 hours apart

Early intensification (4-week cycle; repeat cycle once):
Methotrexate: Intrathecal: 15 mg/dose day 1[total dose/cycle = 15 mg]
Cyclophosphamide: IV: 1000 mg/m2 day 1[total dose/cycle = 1000 mg/m2]
Mercaptopurine: Oral: 60 mg/m2/dose days 1 to 14[total dose/cycle = 840 mg/m2]
Cytarabine: SubQ: 75 mg/m2/dose days 1 to 4 and 8 to 11[total dose/cycle = 600 mg/m2]
Vincristine: IV: 2 mg/dose days 15 and 22[total dose/cycle = 4 mg]
Asparaginase (E. coli): SubQ, IM: 6000 units/m2/dose days 15, 18, 22, and 25[total dose/cycle = 24,000 units/m2]
Filgrastim: SubQ: 5 mcg/kg/day starting day 2; continue at least 14 days and until ANC ≥5000/mm3 on two draws, 24 hours apart

CNS prophylaxis/interim maintenance (12-week duration; with cranial irradiation days 1 to 12):
Methotrexate: Intrathecal: 15 mg/dose days 1, 8, 15, 22, and 29[total dose/cycle = 75 mg]
Mercaptopurine: Oral: 60 mg/m2/dose days 1 to 70[total dose/cycle = 4200 mg/m2]
Methotrexate: Oral: 20 mg/m2/dose days 36, 43, 50, 57, and 64[total dose/cycle = 100 mg/m2]

Late intensification (8-week cycle):
Doxorubicin: IV: 30 mg/m2/dose days 1, 8, and 15[total dose/cycle = 90 mg/m2]
Vincristine: IV: 2 mg/dose days 1, 8, and 15[total dose/cycle = 6 mg]
Dexamethasone: Oral: 10 mg/m2/dose days 1 to 14[total dose/cycle = 140 mg/m2]
Cyclophosphamide: IV: 1000 mg/m2 day 29[total dose/cycle = 1000 mg/m2]
Thioguanine: Oral: 60 mg/m2/dose days 29 to 42[total dose/cycle = 840 mg/m2]
Cytarabine: SubQ: 75 mg/m2/dose days 29 to 32 and 36 to 39[total dose/cycle = 600 mg/m2]

Maintenance (continue until 24 months from diagnosis):
Vincristine: IV: 2 mg/dose day 1 every 4 weeks[total dose/4 weeks = 2 mg]
Prednisone: Oral: 60 mg/m2/dose days 1 to 5 every 4 weeks[total dose/4 weeks = 300 mg/m2]
Mercaptopurine: Oral: 60 mg/m2/dose days 1 to 28[total dose/phase = 1680 mg/m2]
Methotrexate: Oral: 20 mg/m2/dose days 1, 8, 15, and 22[total dose/phase = 80 mg/m2]

CLOVE

(relapsed/refractory; persistent minimal residual disease; bridging regimen to hematopoietic stem cell transplant; ≤21 years of age)
Clofarabine: IV: 20 to 30 mg/m2/day days 1 to 5[total dose/cycle = 100 to 150 mg/m2]
Cyclophosphamide: IV: 300 to 340 mg/m2/day days 1 to 5[total dose/cycle = 1,500 to 1,700 mg/m2]
Etoposide: IV: 100 mg/m2/day days 1 to 5[total dose/cycle = 500 mg/m2]

Hyper-CVAD + Imatinib

Cycle A: (Cycles 1, 3, 5, and 7)
Imatinib: Oral: 400 mg/day days 1 to 14[total dose/cycle = 5,600 mg]
Cyclophosphamide: IV: 300 mg/m2 every 12 hours, for 6 doses, days 1, 2, and 3[total dose/cycle = 1,800 mg/m2]
Mesna: IV 600 mg/m2/day continuous infusion days 1, 2, and 3[total dose/cycle = 1,800 mg/m2]
Vincristine: IV: 2 mg/day days 4 and 11[total dose/cycle = 4 mg]
Doxorubicin: IV: 50 mg/m2/day continuous infusion day 4[total dose/cycle = 50 mg/m2]
Dexamethasone: Oral, IV: 40 mg/day days 1 to 4 and 11 to 14[total dose/cycle = 320 mg]

Cycle B: (Cycles 2, 4, 6, and 8)
Imatinib: Oral: 400 mg/day days 1 to 14[total dose/cycle = 5,600 mg]
Methotrexate: IV: 1 g/m2/day continuous infusion day 1[total dose/cycle = 1 g/m2]
Leucovorin: IV: 50 mg then 15 mg every 6 hours, for 8 doses (start 12 hours after the end of the methotrexate infusion)[total dose/cycle = 170 mg]
Cytarabine: IV: 3 g/m2 every 12 hours for 4 doses, days 2 and 3[total dose/cycle = 12 g/m2]
Repeat every 6 weeks in the following sequence: ABABABAB

CNS Prophylaxis
Methotrexate: Intrathecal: 12 mg/day day 2[total dose/cycle = 12 mg/day] or 6 mg into Ommaya day 2[total dose/cycle = 6 mg/day]
Cytarabine: Intrathecal: 100 mg/day day 7 or 8[total dose/cycle = 100 mg/day]
Repeat cycle every 3 weeks for 3 or 4 cycles

Maintenance (POMP)
Imatinib: Oral: 600 mg/day[total dose/cycle = 18,000 mg]
Vincristine: IV: 2 mg/dose once each month[total dose/cycle = 2 mg]
Prednisone: Oral: 200 mg once daily for 5 days each month (beginning on the day vincristine is administered)[total dose/cycle = 1,000 mg]
Repeat cycle every month (except months 6 and 13) for 13 months

Intensification
Imatinib: Oral: 400 mg/day days 1 to 14[total dose/cycle = 5,600 mg]
Cyclophosphamide: IV: 300 mg/m2 every 12 hours, for 6 doses, days 1, 2, and 3[total dose/cycle = 1,800 mg/m2]
Mesna: IV: 600 mg/m2/day continuous infusion days 1, 2, and 3[total dose/cycle = 1,800 mg/m2]
Vincristine: IV: 2 mg/day days 4 and 11[total dose/cycle = 4 mg]
Doxorubicin: 50 mg/m2/day continuous infusion day 4[total dose/cycle = 50 mg/m2]
Dexamethasone: IV or Oral: 40 mg/day days 1 to 4 and 11 to 14[total dose/cycle = 320 mg]
Cycle is given in months 6 and 13 during maintenance

Variation 1:

Cycle A: (Cycles 1, 3, 5, and 7)
Cyclophosphamide: IV: 300 mg/m2 every 12 hours, for 6 doses, days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]
Mesna: IV: 1,200 mg/m2/day continuous infusion days 1, 2, and 3 [total dose/cycle = 3,600 mg/m2]
Vincristine: IV: 2 mg/day days 4 and 11 [total dose/cycle = 4 mg]
Doxorubicin: IV: 50 mg/m2 day 4 [total dose/cycle = 50 mg/m2]
Dexamethasone: (route not specified): 40 mg/day days 1 to 4 and 11 to 14 [total dose/cycle = 320 mg]

Cycle B: (Cycles 2, 4, 6, and 8)
Methotrexate: IV: 1 g/m2 continuous infusion day 1 [total dose/cycle = 1g/m2]
Leucovorin: (route not specified): 15 mg every 6 hours, for 8 doses (start 12 hours after end of methotrexate infusion) [total dose/cycle = 120 mg]
Cytarabine: IV: 3 g/m2 every 12 hours, for 4 doses, days 2 and 3 [total dose/cycle = 12 g/m2]
Methylprednisolone: IV: 50 mg twice daily, for 6 doses, days 1, 2, and 3 [total dose/cycle = 300 mg]
Repeat every 6 weeks in the following sequence: ABABABAB


CNS Prophylaxis
Methotrexate: Intrathecal: 12 mg/day day 2 [total dose/cycle = 12 mg]
or 6 mg/day into Ommaya day 2 [total dose/cycle = 6 mg]
Cytarabine: Intrathecal: 100 mg day 8 [total dose/cycle = 100 mg]
Repeat cycle every 3 weeks

Maintenance (POMP)
Mercaptopurine: Oral: 50 mg 3 times/day [total dose/cycle = 4,200 to 4,650 mg]
Vincristine: IV: 2 mg day 1 [total dose/cycle = 2 mg]
Methotrexate: Oral: 20 mg/m2/day days 1, 8, 15, and 22 [total dose/cycle = 80 mg/m2]
Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1,000 mg]
or
Mercaptopurine: IV: 1 g/m2/day days 1 to 5 [total dose/cycle = 5 g/m2]
Vincristine: IV: 2 mg day 1 [total dose/cycle = 2 mg]
Methotrexate: IV: 10 mg/m2/day days 1 to 5 [total dose/cycle = 50 mg/m2]
Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1,000 mg]
Repeat cycles every month for 2 years

Variation 2: 

Cycle A: (Cycles 1, 3, 5, and 7)
Cyclophosphamide: IV: 300 mg/m2 every 12 hours, for 6 doses, days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]
Mesna: IV: 600 mg/m2/day continuous infusion days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]
Vincristine: IV: 2 mg/day days 4 and 11 [total dose/cycle = 4 mg]
Doxorubicin: IV: 50 mg/m2 day 4 [total dose/cycle = 50 mg/m2]
Dexamethasone: Oral, IV: 40 mg/day days 1 to 4 and 11 to 14 [total dose/cycle = 320 mg]

Cycle B: (Cycles 2, 4, 6, and 8)
Methotrexate: IV: 1 g/m2 continuous infusion day 1 [total dose/cycle = 1 g/m2]
Leucovorin: IV: 50 mg (start 12 hours after end of methotrexate infusion)
followed by IV: 15 mg every 6 hours, for 8 doses [total dose/cycle = 170 mg]
Cytarabine: IV: 3 g/m2 every 12 hours, for 4 doses, days 2 and 3 [total dose/cycle = 12 g/m2]
Repeat every 6 weeks in the following sequence: ABABABAB

CNS Prophylaxis
Methotrexate: Intrathecal: 12 mg day 2 [total dose/cycle = 12 mg]
or 6 mg into Ommaya day 2 [total dose/cycle = 6 mg]
Cytarabine: Intrathecal: 100 mg day 7 [total dose/cycle = 100 mg]
Repeat cycle every 3 weeks

Variation 3:

Cycle A: (Cycles 1, 3, 5, and 7)
Cyclophosphamide: IV: 300 mg/m2 every 12 hours, for 6 doses, days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]
Mesna: IV: 600 mg/m2/day continuous infusion days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]
Vincristine: IV: 2 mg/day days 4 and 11 [total dose/cycle = 4 mg]
Doxorubicin: IV: 50 mg/m2 continuous infusion day 4 [total dose/cycle = 50 mg/m2]
Dexamethasone: Oral, IV: 40 mg/day days 1 to 4 and 11 to 14 [total dose/cycle = 320 mg]

Cycle B: (Cycles 2, 4, 6, and 8)
Methotrexate: IV: 200 mg/m2 day 1 followed by IV: 800 mg/m2 continuous infusion day 1 [total dose/cycle = 1 g/m2]
Leucovorin: IV: 50 mg (start 12 hours after end of methotrexate infusion) followed by IV: 15 mg every 6 hours, for 8 doses [total dose/cycle = 170 mg/m2]
Cytarabine: IV: 3 g/m2 every 12 hours, for 4 doses, days 2 and 3 [total dose/cycle = 12 g/m2]
Repeat every 6 weeks in the following sequence: ABABABAB

CNS Prophylaxis
Methotrexate: Intrathecal: 12 mg day 2 [total dose/cycle = 12 mg]
or 6 mg into Ommaya day 2 [total dose/cycle = 6 mg]
Cytarabine: Intrathecal: 100 mg day 7 or 8 [total dose/cycle = 100 mg]
Repeat cycles every 3 weeks for 6 or 8 cycles 

Maintenance (POMP)
Mercaptopurine: Oral: 50 mg 3 times/day [total dose/cycle = 4,200 to 4,650 mg]
Vincristine: IV: 2 mg day 1 [total dose/cycle = 2 mg]
Methotrexate: Oral, IV: 20 mg/m2/ day days 1, 8, 15, and 22 [total dose/cycle = 80 mg/m2]
Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1,000 mg]
or 
Mercaptopurine: IV: 1 g/m2/day days 1 to 5 [total dose/cycle = 5 g/m2]
Vincristine: IV: 2 mg day 1 [total dose/cycle = 2 mg]
Methotrexate: IV: 10 mg/m2/day days 1 to 5 [total dose/cycle = 50 mg/m2]
Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1,000 mg]
Repeat cycles every month (except months 7 and 11 or 9 and 12) for 2 years

Intensification
Etoposide: IV: 100 mg/m2/day days 1 to 5 [total dose/cycle = 500 mg/m2]
Pegaspargase: IV: 2,500 units/m2 day 1 [total dose/cycle = 2,500 units/m2]
Given during months 9 and 12 of maintenance
or
Methotrexate: IV: 100 mg/m2/day days 1, 8, 15, and 22 [total dose/cycle = 400 mg/m2]
Asparaginase: IV: 20,000 units/day days 2, 9, 16, and 23 [total dose/cycle = 80,000 units]
Given during months 7 and 11 of maintenance

Variation 4:

Cycle A: (Cycles 1, 3, 5, and 7)
Cyclophosphamide: IV: 300 mg/m2 every 12 hours, for 6 doses, days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]
Mesna: IV: 600 mg/m2/day continuous infusion days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]
Vincristine: IV: 2 mg/day days 4 and 11 [total dose/cycle = 4 mg]
Doxorubicin: IV: 50 mg/m2day 4 [total dose/cycle = 50 mg/m2]
Dexamethasone: (route not specified): 40 mg/day days 1 to 4 and 11 to 14 [total dose/cycle = 320 mg]
Cycle B: (Cycles 2, 4, 6, and 8) Methotrexate: IV: 200 mg/m2 day 1
followed by IV: 800 mg/m2 continuous infusion day 1 [total dose/cycle = 1 g/m2]
Leucovorin: (route not specified): 15 mg every 6 hours, for 8 doses (start 24 hours after end of methotrexate infusion) [total dose/cycle = 120 mg]
Cytarabine: IV: 3 g/m2 every 12 hours, for 4 doses, days 2 and 3 [total dose/cycle = 12 g/m2]
Methylprednisolone: IV: 50 mg twice daily, for 6 doses, days 1, 2, and 3 [total dose/cycle = 300 mg]
Repeat every 6 weeks in the following sequence: ABABABAB

CNS Prophylaxis
Methotrexate: Intrathecal: 12 mg day 2 [total dose/cycle = 12 mg]
Cytarabine: Intrathecal: 100 mg day 8 [total dose/cycle = 100 mg]
Repeat cycle every 3 weeks for 4 or 8 cycles

Maintenance (POMP)
Mercaptopurine: Oral: 50 mg 3 times/day [total dose/cycle = 4,200 to 4,650 mg]
Vincristine: IV: 2 mg day 1 [total dose/cycle = 2 mg]
Methotrexate: Oral: 20 mg/m2/day days 1, 8, 15, and 22 [total dose/cycle = 80 mg/m2]
Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1,000 mg]
or
Mercaptopurine: IV: 1 g/m2/day days 1 to 5 [total dose/cycle = 5 g/m2]
Vincristine: IV: 2 mg day 1 [total dose/cycle = 2 mg]
Methotrexate: IV: 10 mg/m2/day days 1 to 5 [total dose/cycle = 50 mg/m2]
Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1,000 mg]
or
Interferon alfa: SubQ: 5 million units/m2 daily [total dose/cycle = 140 to 155 million units/m2]
Cytarabine: SubQ: 10 mg daily [total dose/cycle = 280 to 310 mg]
Repeat cycles every month for 2 years

Variation 5:


Cycle A: (Cycles 1, 4, 6, and 8)
Cyclophosphamide: IV: 300 mg/m2 every 12 hours, for 6 doses, days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]
Mesna: IV: 600 mg/m2/day continuous infusion days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]
Vincristine: IV: 2 mg/day days 4 and 11 [total dose/cycle = 4 mg]
Doxorubicin: IV: 50 mg/m2 continuous infusion day 4 [total dose/cycle = 50 mg/m2]
Dexamethasone: Oral, IV: 40 mg/day days 1 to 4 and 11 to 14 [total dose/cycle = 320 mg]

Cycle B: (Cycles 3, 5, 7, and 9)
Methotrexate: IV: 200 mg/m2 day 1 followed by IV: 800 mg/m2 continuous infusion day 1 [total dose/cycle = 1 g/m2]
Leucovorin: IV: 50 mg (start 12 hours after end of methotrexate infusion) followed by IV: 15 mg every 6 hours, for 8 doses [total dose/cycle = 170 mg]
Cytarabine: IV: 3 g/m2 every 12 hours, for 4 doses, days 2 and 3 [total dose/cycle = 12 g/m2]

Cycle C: Liposomal Daunorubicin/Cytarabine (Cycle 2):
Daunorubicin, liposomal: IV: 150 mg/m2/day days 1 and 2 [total dose/cycle = 300 mg/m2]
Cytarabine: IV: 1.5 g/m2/day continuous infusion days 1 and 2 [total dose/cycle = 3 g/m2]
Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1,000 mg]
Administer in the following sequence: ACBABABA (Cycle C does not repeat)

CNS Prophylaxis
Methotrexate: Intrathecal: 12 mg day 2 [total dose/cycle = 12 mg]
or 6 mg into Ommaya day 2 [total dose/cycle = 6 mg]
Cytarabine: Intrathecal: 100 mg day 7 or 8 [total dose/cycle = 100 mg]
Repeat cycle every 3 weeks for 6 or 8 cycles

Maintenance (POMP)
Mercaptopurine: IV: 1 g/m2/day days 1 to 5 [total dose/cycle = 5 g/m2]
Vincristine: IV: 2 mg day 1 [total dose/cycle = 2 mg]
Methotrexate: IV: 10 mg/m2/day days 1 to 5 [total dose/cycle = 50 mg/m2]
Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1,000 mg]
Repeat cycles monthly, except months 6, 7, 18, and 19 for 3 years

Intensification
Methotrexate: IV: 100 mg/m2/day days 1, 8, 15, and 22 [total dose/cycle = 400 mg/m2]
Asparaginase: IV: 20,000 units/day days 2, 9, 16, and 23 [total dose/cycle = 80,000 units]
Given during months 6 and 18 of maintenance
Cyclophosphamide: IV: 300 mg/m2 every 12 hours, for 6 doses, days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]
Mesna: IV: 600 mg/m2/day continuous infusion days 1, 2, and 3 [total dose/cycle = 1,800 mg/m2]
Vincristine: IV: 2 mg/day days 4 and 11 [total dose/cycle = 4 mg]
Doxorubicin: IV: 50 mg/m2/day continuous infusion day 4 [total dose/cycle = 50 mg/m2]
Dexamethasone: Oral, IV: 40 mg/day days 1 to 4 and 11 to 14 [total dose/cycle = 320 mg]
Given during months 7 and 19 of maintenance
Remission induction:
Daunorubicin: IV: 50 mg/m2/day days 1, 2, and 3 [total dose/cycle = 150 mg/m2]
Vincristine: IV: 2 mg/day days 1, 8, 15, and 22 [total dose/cycle = 8 mg]
Prednisone: Oral: 60 mg/m2/day days 1 to 28 [total dose/cycle = 1680 mg/m2]
Asparaginase: IM: 6000 units/m2/day days 17 to 28 [total dose/cycle = 72,000 units/m2]
If residual leukemia in bone marrow on day 14:
Daunorubicin: IV: 50 mg/m2 day 15 [total dose/cycle = 50 mg/m2]
If residual leukemia in bone marrow on day 28:
Daunorubicin: IV: 50 mg/m2/day days 29 and 30 [total dose/cycle = 100 mg/m2]
Vincristine: IV: 2 mg/day days 29 and 36 [total dose/cycle = 4 mg]
Prednisone: Oral: 60 mg/m2/day days 29 to 42 [total dose/cycle = 840 mg/m2]
Asparaginase: IM: 6000 units/m2/day days 29 to 35 [total dose/cycle = 42,000 units/m2]

Consolidation therapy:
Treatment A (cycles 1, 3, 5, and 7)
Daunorubicin: IV: 50 mg/m2/day days 1 and 2 [total dose/cycle = 100 mg/m2]
Vincristine: IV: 2 mg/day days 1 and 8 [total dose/cycle = 4 mg]
Prednisone: Oral: 60 mg/m2/day days 1 to 14 [total dose/cycle = 840 mg/m2]
Asparaginase: IM: 12,000 units/m2/day days 2, 4, 7, 9, 11, and 14 [total dose/cycle = 72,000 units/m2]

Treatment B (cycles 2, 4, 6, and 8)
Teniposide: IV: 165 mg/m2/day days 1, 4, 8, and 11 [total dose/cycle = 660 mg/m2]
Cytarabine: IV: 300 mg/m2/day days 1, 4, 8, and 11 [total dose/cycle = 1200 mg/m2]

Treatment C (cycle 9)
Methotrexate: IV: 690 mg/m2 continuous infusion over 42 hours day 1 [total dose/cycle = 690 mg/m2]
Leucovorin: IV: 15 mg/m2 every 6 hours for 12 doses (start at end of methotrexate infusion) [total dose/cycle = 180 mg/m2]
Administer remission induction regimen for one cycle only. Repeat consolidation cycle every 28 days.

MTX/6-MP/VP

(Maintenance)
Methotrexate: Oral: 20 mg/m2 weekly [total dose/cycle = 80 mg/m2]
Mercaptopurine: Oral: 75 mg/m2/day [total dose/cycle = 2250 mg/m2]
Vincristine: IV: 1.5 mg/m2 day 1 [total dose/cycle = 1.5 mg/m2]
Prednisone: Oral: 40 mg/m2/day days 1 to 5 [total dose/cycle = 200 mg/m2]
Repeat monthly for 2-3 years
Maintenance:
Mercaptopurine: Oral: 50 mg 3 times/day [total dose/cycle = 4200-4650 mg]
Methotrexate: Oral: 20 mg/m2 once weekly [total dose/cycle = 80 mg/m2]
Vincristine: IV: 2 mg day 1 [total dose/cycle = 2 mg]
Prednisone: Oral: 200 mg/day days 1 to 5 [total dose/cycle = 1000 mg]
Repeat cycle monthly for 2 years
Induction cycle:
Vincristine: IV: 0.4 mg/day continuous infusion days 1 to 4 and 24 to 27 [total dose/cycle = 3.2 mg]
Doxorubicin: IV: 12 mg/m2/day continuous infusion days 1 to 4 and 24 to 27 [total dose/cycle = 96 mg/m2]
Dexamethasone: Oral: 40 mg/day days 1 to 4, 9 to 12, 17 to 20, 24 to 27, 32 to 35, and 40 to 43 [total dose/cycle = 960 mg]
Cyclophosphamide: IV: 1 g/m2 day 24[total dose/cycle = 1 g/m2]
Administer one cycle only

Acute Myeloid Leukemia

Clofarabine-Cytarabine

(relapsed/refractory, 18 to 70 years of age)

Induction:
Filgrastim: SubQ: 5 mcg/kg (round to nearest vial size) once daily beginning day 0 and continuing until the ANC ≥2,000/mm3 for 2 consecutive days
Clofarabine: IV: 25 mg/m2/day over 1 hour days 1 to 5 [total dose/cycle = 125 mg/m2]
Cytarabine: IV: 2,000 mg/m2/day over 2 hours days 1 to 5 (beginning 4 hours after start of clofarabine) [total dose/cycle = 10,000 mg/m2]
A second induction cycle may be administered after day 21 if needed, up to a maximum of 2 induction cycles

Consolidation:
Filgrastim: SubQ: 5 mcg/kg (round to nearest vial size) once daily beginning day 0 and continuing until the ANC ≥2,000/mm3 for 2 consecutive days
Clofarabine: IV: 20 mg/m2/day over 1 hour days 1 to 5 [total dose/cycle = 100 mg/m2]
Cytarabine: IV: 1,000 mg/m2/day over 2 hours days 1 to 5 (beginning 4 hours after start of clofarabine) [total dose/cycle = 5,000 mg/m2]
Repeat consolidation every 21 days for 1 or 2 cycles, up to a maximum of 2 consolidation cycles
Variation 1 (induction):
Etoposide: IV: 80 mg/m2/day over 1 hour days 1 to 6 [total dose/cycle = 480 mg/m2]
Cytarabine: IV: 1,000 mg/m2/day over 6 hours days 1 to 6 [total dose/cycle = 6,000 mg/m2]
Mitoxantrone: IV: 6 mg/m2/day days 1 to 6 (3 hours after the end of the cytarabine infusion) [total dose/cycle = 36 mg/m2]
Patients in complete remission proceeded to consolidation therapy

Variation 2:
Etoposide: IV: 100 mg/m2/day over 2 hours days 1 to 5 [total dose/cycle = 500 mg/m2]
Cytarabine: IV: 1,000 mg/m2/day days 1 to 5 [total dose/cycle = 5,000 mg/m2]
Mitoxantrone: IV: 8 mg/m2/day days 1 to 5 [total dose/cycle = 40 mg/m2]

Cladribine: IV: 5 mg/m2/day over 2 hours days 1 to 5 [total dose/cycle = 25 mg/m2]

Cytarabine: IV: 2 g/m2/day over 4 hours days 1 to 5 (begin 2 hours after cladribine) [total dose/cycle = 10 g/m2]

Filgrastim: SubQ: 300 mcg daily days 0 to 5 (start 24 hours prior to chemotherapy; for a total of 6 days) [total dose/cycle = 1800 mcg]

May administer a second induction cycle if needed

Cladribine: IV: 5 mg/m2/day over 2 hour days 1 to 5 [total dose/cycle = 25 mg/m2]
Cytarabine: IV: 2 g/m2/day over 4 hours days 1 to 5 (begin 2 hours after cladribine) [total dose/cycle = 10 g/m2]
Mitoxantrone: IV: 10 mg/m2/day days 1 to 3 [total dose/cycle = 30 mg/m2]
Filgrastim: SubQ: 300 mcg daily days 0 to 5 (start 24 hours prior to chemotherapy; for a total of 6 days) [total dose/cycle = 1800 mcg]
May administer a second induction cycle if needed
Variation 1:
Fludarabine: IV: 30 mg/m2/day over 30 minutes days 1 to 5 [total dose/cycle = 150 mg/m2]
Cytarabine: IV: 2 g/m2/day over 4 hours days 1 to 5 (begin 4 hours after fludarabine infusion) [total dose/cycle = 10 g/m2]
Filgrastim: SubQ: 300 mcg 12 hours prior to start of fludarabine then 300 mcg/day days 2 through 5 [total dose/cycle = 1500 mcg]
followed by Filgrastim: SubQ: 300 mcg/day beginning one week after the end of treatment and continuing until complete neutrophil recovery

Variation 2:
Fludarabine: IV: 30 mg/m2/day over 30 minutes days 1 to 5 [total dose/cycle = 150 mg/m2]
Cytarabine: IV: 2 g/m2/day over 4 hours days 1 to 5 (begin 3.5 hours after end of fludarabine infusion) [total dose/cycle = 10 g/m2]
Filgrastim: SubQ: 5 mcg/kg/day beginning 24 hours prior to start of fludarabine and continuing until ANC >500 mm3
May repeat cycle one time for partial remission

Variation 3:
Fludarabine: IV: 30 mg/m2/day over 30 minutes days 1 to 5 [total dose/cycle = 150 mg/m2]
Cytarabine: IV: 2 g/m2/day over 2 hours days 1 to 5 (begin 4 hours after the start of fludarabine infusion) [total dose/cycle = 10 g/m2]
Filgrastim: SubQ or IV: 300 mcg/day beginning the day prior to start of chemotherapy and continuing during chemotherapy and until ANC >1000 mm3
May receive a second cycle

Variation 4:
Fludarabine: IV: 25 mg/m2/day over 30 minutes days 1 to 5 [total dose/cycle = 125 mg/m2]
Cytarabine: IV: 2 g/m2/day over 4 hours days 1 to 5 (begin 4 hours after start of fludarabine infusion) [total dose/cycle = 10 g/m2]
Filgrastim: SubQ: 5 mcg/kg/day beginning 24 hours prior to start of cytarabine and continuing until ANC >500 mm3
May repeat cycle in patients with complete remission and partial remission
Variation 1:
Fludarabine: IV: 30 mg/m2/day over 30 minutes days 1 to 5 [total dose/cycle = 150 mg/m2]
Cytarabine: IV: 2 g/m2/day over 4 hours days 1 to 5 (begin 4 hours after the start of fludarabine) [total dose/cycle = 10 g/m2]
Idarubicin: IV: 10 mg/m2/day days 1, 2, and 3 [total dose/cycle = 30 mg/m2]
Filgrastim: SubQ: 5 mcg/kg from day 6 until ANC >500/mm3

Variation 2:
Fludarabine: IV: 30 mg/m2/day over 30 minutes days 1 to 5 [total dose/cycle = 150 mg/m2]
Cytarabine: IV: 2 g/m2/day over 2 hours days 1 to 5 (begin 4 hours after the start of fludarabine infusion) [total dose/cycle = 10 g/m2]
Idarubicin: IV: 8 mg/m2/day over 30 minutes days 1, 2, and 3 [total dose/cycle = 24 mg/m2]
Filgrastim: SubQ or IV: 300 mcg/day beginning the day prior to start of chemotherapy and continuing during chemotherapy and until ANC >1000/mm3
May receive up to 2 cycles

Variation 3:
Fludarabine: IV: 30 mg/m2/day over 30 minutes days 1 to 4 [total dose/cycle = 120 mg/m2]
Cytarabine: IV: 2 g/m2/day over 4 hours days 1 to 4 (begin 4 hours after fludarabine treatment) [total dose/cycle = 8 g/m2]
Idarubicin: IV: 10 mg/m2/day days 1, 2, and 3 [total dose/cycle = 30 mg/m2]
Filgrastim: Sub Q: see article for dose and frequency
Induction:
Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 5 [total dose/cycle = 500 mg/m2]
Daunorubicin: IV: 45 mg/m2/day IV bolus days 1 and 2 [total dose/cycle = 90 mg/m2]
May administer a second induction cycle if needed

Postremission:
Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 5 [total dose/cycle = 500 mg/m2]
Daunorubicin: IV: 45 mg/m2/day IV bolus days 1 and 2 [total dose/cycle = 90 mg/m2]
Administer 2 courses
Variation 1:
Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 7 [total dose/cycle = 700 mg/m2]
Daunorubicin: IV: 45 mg/m2/day IV bolus days 1, 2, and 3 [total dose/cycle = 135 mg/m2]
May administer a second induction cycle if needed

Variation 2 (≥60 years of age):
Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 7 [total dose/cycle = 700 mg/m2]
Daunorubicin: IV: 30 mg/m2/day days 1, 2, and 3 [total dose/cycle = 90 mg/m2]
May administer a second induction cycle if needed (at a reduced dose of daunorubicin [45 mg/m2])

Variation 3 (between 17 and 60 years of age):
Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 7 [total dose/cycle = 700 mg/m2]
Daunorubicin: IV: 90 mg/m2/day IV bolus days 1, 2, and 3 [total dose/cycle = 270 mg/m2]
May administer a second induction cycle if needed

Variation 4 (<60 years of age):
Cytarabine: IV: 200 mg/m2/day continuous infusion days 1 to 7 [total dose/cycle = 1400 mg/m2]
Daunorubicin: IV: 45 mg/m2/day IV bolus days 1, 2, and 3 [total dose/cycle = 135 mg/m2]
May administer a second induction cycle if needed
Induction:
Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 7 [total dose/cycle = 700 mg/m2]
Daunorubicin: IV: 50 mg/m2/day days 1, 2, and 3 [total dose/cycle = 150 mg/m2]
Etoposide: IV: 75 mg/m2/day over 1 hour days 1 to 7 [total dose/cycle = 525 mg/m2]
Up to 3 induction cycles may be given based on individual response

Consolidation:
Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 5 [total dose/cycle = 500 mg/m2]
Daunorubicin: IV: 50 mg/m2/day IV bolus days 1 and 2 [total dose/cycle = 100 mg/m2]
Etoposide: IV: 75 mg/m2/day over 1 hour days 1 to 5 [total dose/cycle = 375 mg/m2]
Administer 2 courses

Induction:
Variation 1:
Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 7 [total dose/cycle = 700 mg/m2]
Idarubicin: IV: 12 mg/m2/day slow IV infusion days 1, 2, and 3 [total dose/cycle = 36 mg/m2]
May administer a second induction cycle if needed
Variation 2:
Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 7 [total dose/cycle = 700 mg/m2]
Idarubicin: IV: 13 mg/m2/day slow IV infusion days 1, 2, and 3 [total dose/cycle = 39 mg/m2]
May administer a second induction cycle if needed

Consolidation:
Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 5 [total dose/cycle = 500 mg/m2]
Idarubicin: IV: 13 mg/m2/day IV bolus days 1 and 2 [total dose/cycle = 26 mg/m2]
Administer 2 courses

Cytarabine-Mitoxantrone

7 + 3 Induction
5 + 2 Consolidation

Induction:
Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 7 [total dose/cycle = 700 mg/m2]
Mitoxantrone: IV: 12 mg/m2/day days 1, 2, and 3 [total dose/cycle = 36 mg/m2]

Reinduction if needed:
Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 5 [total dose/cycle = 500 mg/m2]
Mitoxantrone: IV: 12 mg/m2/day days 1 and 2 [total dose/cycle = 24 mg/m2]

Consolidation:
Cytarabine: IV: 100 mg/m2/day continuous infusion days 1 to 5 [total dose/cycle = 500 mg/m2]
Mitoxantrone: IV: 12 mg/m2/day days 1 and 2 [total dose/cycle = 24 mg/m2]
Administered every 28 days for a total of 2 cycles

Cytarabine-Daunorubicin

Induction:
Cytarabine: IV: 2 g/m2/day over 1 hour every 12 hours days 1 to 6 (12 total doses)[total dose/cycle = 24 g/m2]
Daunorubicin: IV: 45 mg/m2/day IV bolus days 7 to 9[total dose/cycle = 135 mg/m2]

Cytarabine-Daunorubicin-Etoposide

Daunorubicin: IV: 50 mg/m2/day days 1, 2, and 3[total dose/cycle = 150 mg/m2]
Cytarabine: IV: 3 g/m2/dose over 3 hours every 12 hours days 1, 3, 5, and 7 (8 total doses)[total dose/cycle = 24 g/m2]
Etoposide: IV: 75 mg/m2/day days 1 to 7[total dose/cycle = 525 mg/m2]

Up to 3 induction cycles may be given based on individual response
Induction:
Variation 1 (ages 14 to 50 years):Cytarabine: IV: 3 g/m2 over 2 hours every 12 hours days 1 to 6 (total of 12 doses)[total dose/cycle = 36 g/m2]
May administer a second induction cycle if needed
Variation 2 (ages >50 years):Cytarabine: IV: 2 g/m2 over 2 hours every 12 hours days 1 to 6 (total of 12 doses)[total dose/cycle = 24 g/m2]
May administer a second induction cycle if needed

Consolidation:
Variation 1: Cytarabine: IV: 3 g/m2 over 3 hours every 12 hours on days 1, 3, and 5 (total of 6 doses)[total dose/cycle = 18 g/m2]
Repeat cycle every 4 to 5 weeks (depending on marrow recovery) for a total of 4 postremission cycles
Variation 2: Cytarabine: IV: 400 mg/m2/day continuous infusion on days 1 to 5[total dose/cycle = 2000 mg/m2]
Repeat cycle every 4 to 5 weeks (depending on marrow recovery) for a total of 4 postremission cycles
Variation 3: Cytarabine: IV: 100 mg/m2/day continuous infusion on days 1 to 5[total dose/cycle = 500 mg/m2]
Repeat cycle every 4 to 5 weeks (depending on marrow recovery) for a total of 4 postremission cycles
Variation 4 (≥60 years of age):Cytarabine: IV: 100 mg/m2/day continuous infusion on days 1 to 5[total dose/cycle = 500 mg/m2]
Repeat cycle every 28 days for a total of 4 consolidation cycles
Variation 5 (≤50 years of age):Cytarabine: IV: 3 g/m2 every 12 hours on days 1 to 3 (total of 6 doses)[total dose/cycle = 18 g/m2]
Administer a total of 3 consolidation cycles
Variation 6 (>50 years of age)Cytarabine: IV: 2 g/m2 every 12 hours on days 1 to 3 (total of 6 doses)[total dose/cycle = 12 g/m2]
Administer a total of 3 consolidation cycles
Variation 7 (>65 years of age):Cytarabine: SubQ: 10 mg/m2/dose every 12 hours days 1 to 14[total dose/cycle = 280 mg/m2]
Repeat cycle every 6 weeks for 18 months
Variation 1 (>50 years of age):Cytarabine: SubQ: 20 mg/m2/day days 1 to 14[total dose/cycle = 280 mg/m2]
Repeat cycle every 28 days for at least 4 cycles
Variation 2 (>65 years of age):Cytarabine: SubQ: 10 mg/m2/day every 12 hours days 1 to 21[total dose/cycle = 420 mg/m2]
After 15 days, a second induction course may be administered if needed
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