Page 142 - 2019_05-HaematologicaMondo-web

M. Burke et al.
Table 1. AALL1131 very high-risk treatment regimen. Experimental Arm 1
Control Arm
CPM (1 g/n2) D29
ARAC (75 mg/m2) D29-32, D36-39 MP (60 mg/m2) D29-42
VCR (1.5 mg/m2, 2 mg max) D43, 50 PEG-ASP (2500 IU/m2) D43
Induction
(same for Exp1 and CA)
IT ARAC D1a
VCR (1.5 mg/m2, 2 mg max) D1, 8, 15, 22 DEX (10 mg/m2/d) D1-14 (<10 years of age) PRED (60 mg/m2/d) D1-28 (>10 years of age) DAUN (25 mg/m2) D1, 8, 15, 22 PEG-ASP (2500 IU/m2) D4
IT MTX D8, 29b
Consolidation Part 1
(same for Exp1 and CA)
CPM (1 gm/m2) D1
ARAC (75 mg/m2) D1-4, D8-11 MP (60 mg/m2) D1-14
VCR (1.5 mg/m2, 2 mg max) D15, 22 PEG-ASP (2500 IU/m2) D15 ITMTXD1,8,15,22
Consolidation Part 2
Interim Maintenance 1
(same for Exp1 and CA)
CPM (440 mg/m2) D29-33 ETOP (100 mg/m2) D29-33 VCR (1.5 mg/m2, 2 mg max) D43, 50 PEG-ASP (2500 IU/m2) D43
IV MTX (5g/m2) followed by leucovorin rescue D1, 15, 29, 43 MP (25 mg/m2) D1-56
VCR (1.5 mg/m2, 2 mg max) D1, 15, 29, 43
IT MTX D1, 29
CPM (1 g/m2) D29
ARAC (75 mg/m2) D29-32, D36-39 TG (60 mg/m2) D29-42
VCR (1.5 mg/m2, 2 mg max) D43, 50 PEG-ASP (2500 IU/m2) D43
IT MTX D29, 36
Delayed Intensification Part 1
(same for Exp1 and CA)
VCR (1.5 mg/m2, 2 mg max) D1, 8, 15 DEX (10 mg/m2/d) D1-14, D15-21 DOX (25 mg/m2) D1, 8, 15 PEG-ASP (2500 IU/m2) D4
IT MTX D1
Delayed Intensification Part 2
Interim Maintenance 2
(same for Exp1 and CA)
IV MTX (100 mg/m2) escalating D1, 11, 21, 31, 41c VCR (1.5 mg/m2, 2 mg max) D1, 11, 21, 31, 41 PEG-ASP (2500 IU/m2) D2, 22
IT MTX D1, 31
Maintenance (12-week cycles)d
(same for Exp1 and CA)
CPM (440 mg/m2) D29-33 ETOP (100 mg/m2) D29-33 VCR (1.5 mg/m2, 2 mg max) D43, 50 PEG-ASP (2500 IU/m2) D43
IT MTX D29, 36
MTX (20 mg/m2) D8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78
MP (75 mg/m2) D1-84
VCR (1.5 mg/m2, 2 mg max) D1, 29, 57
PRED (40 mg/m2) D1-5, 29-33, 57-61
IT MTX D1 (D29 for first 2 cycles for patients who did not receive CNS radiation)
ARAC: cytosine arabinoside; CNS: central nervous system; CPM: cyclophosphamide; DAUN: daunorubicin; DEX: dexamethasone; DOX: doxorubicin; ETOP: etoposide; IT,: intrathecal; MP: mercaptopurine;MTX:methotrexate;PRED:prednisone;PEG-ASP:pegaspargase;TG:thioguanine;VCR:vincristine;aIntrathecal cytarabine:1-1.99 years (30 mg),2-2.99 years (50 mg),≥3 years (70 mg); bintrathecal methotrexate: 1-1.99 years (8 mg), 2-2.99 years (10 mg), 3-8.99 years (12 mg), ≥9 years (15 mg); cthe methotrexate dose was escalated as tolerated 50 mg/m2 every 10 days; dthe total duration of treatment was 2 years for females and 3 years for males from the start of interim maintenance-1 therapy.
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