atients: In study I2301, a total of 93 paediatric, adolescent and young adult patients (from 1 to 22 years old) with Ph+ ALL were enrolled in an open-label, multicentre, sequential cohort, non-randomised phase III trial, and were treated with Glivec (340 mg/m2/day) in combination with intensive chemotherapy after induction therapy. Glivec was administered intermittently in cohorts 1-5, with increasing duration and earlier start of Glivec from cohort to cohort; cohort 1 receiving the lowest intensitiy and cohort 5 receiving the highest intensity of Glivec (longest duration in days with continuous daily Glivec dosing during the first chemotherapy treatment courses). Continuous daily exposure to Glivec early in the course of treatment in combination with chemotherapy in cohort 5-patients (n=50) improved the 4-year event-free survival (EFS) compared to historical controls (n=120), who received standard chemotherapy without Glivec (69.6% vs. 31.6%, respectively). The estimated 4-year OS in cohort 5-patients was 83.6% compared to 44.8% in the historical controls. 20 out of the 50 (40%) patients in cohort 5 received haematopoietic stem cell transplant.
Table 6 Chemotherapy regimen used in combination with imatinib in study I2301
Consolidation block 1
(3 weeks)
VP-16 (100 mg/m2/day, IV): days 1-5
Ifosfamide (1.8 g/m2/day, IV): days 1-5
MESNA (360 mg/m2/dose q3h, x 8 doses/day, IV): days 1-5
G-CSF (5 μg/kg, SC): days 6-15 or until ANC > 1500 post nadir
IT Methotrexate (age-adjusted): day 1 ONLY
Triple IT therapy (age-adjusted): day 8, 15
Consolidation block 2
(3 weeks)
Methotrexate (5 g/m2 over 24 hours, IV): day 1
Leucovorin (75 mg/m2 at hour 36, IV; 15 mg/m2 IV or PO q6h x 6 doses)iii: Days 2 and 3
Triple IT therapy (age-adjusted): day 1
ARA-C (3 g/m2/dose q 12 h x 4, IV): days 2 and 3
G-CSF (5 μg/kg, SC): days 4-13 or until ANC > 1500 post nadir
Reinduction block 1
(3 weeks)
VCR (1.5 mg/m2/day, IV): days 1, 8, and 15
DAUN (45 mg/m2/day bolus, IV): days 1 and 2
CPM (250 mg/m2/dose q12h x 4 doses, IV): days 3 and 4
PEG-ASP (2500 IUnits/m2, IM): day 4
G-CSF (5 μg/kg, SC): days 5-14 or until ANC > 1500 post nadir
Triple IT therapy (age-adjusted): days 1 and 15
DEX (6 mg/m2/day, PO): days 1-7 and 15-21
Intensification block 1
(9 weeks)
Methotrexate (5 g/m2 over 24 hours, IV): days 1 and 15
Leucovorin (75 mg/m2 at hour 36, IV; 15 mg/m2 IV or PO q6h x 6 doses)iii: Days 2, 3, 16, and 17
Triple IT therapy (age-adjusted): days 1 and 22
VP-16 (100 mg/m2/day, IV): days 22-26
CPM (300 mg/m2/day, IV): days 22-26
MESNA (150 mg/m2/day, IV): days 22-26
G-CSF (5 μg/kg, SC): days 27-36 or until ANC > 1500 post nadir
ARA-C (3 g/m2, q12h, IV): days 43, 44
L-ASP (6000 IUnits/m2, IM): day 44
Reinduction block 2
(3 weeks)
VCR (1.5 mg/m2/day, IV): days 1, 8 and 15
DAUN (45 mg/m2/day bolus, IV): days 1 and 2
CPM (250 mg/m2/dose q12h x 4 doses, iv): Days 3 and 4
PEG-ASP (2500 IUnits/m2, IM): day 4
G-CSF (5 μg/kg, SC): days 5-14 or until ANC > 1500 post nadir
Triple IT therapy (age-adjusted): days 1 and 15
DEX (6 mg/m2/day, PO): days 1-7 and 15-21
Intensification block 2
(9 weeks)
Methotrexate (5 g/m2 over 24 hours, IV): days 1 and 15
Leucovorin (75 mg/m2 at hour 36, IV; 15 mg/m2 IV or PO q6h x 6 doses)iii: d
