Table 1.

CCG 1953 therapy detail


Phase

Treatment regimen
Induction, 4 wk  
    CPM   250 mg/m2 every 12 h × 4 doses, days 2, 3  
    DXM   10 mg/m2 orally 3 times daily, days 0-20, no taper  
    VCR   0.05 mg/kg, days 0, 14; 0.03 mg/kg day 7  
    DNM   2 mg/kg/dose intravenously over 30 min for patients age ≤ 90 d  
  2 mg/kg/d; 4 mg/kg over 48 h, age > 90 d to < 6 mo  
  2.5 mg/kg/d; 5 mg/kg over 48 h, age 6 to < 9 mo  
  3 mg/kg/d; 6 mg/kg over 48 h, age ≥ 9 mo, as a 48-h continuous infusion through central venous catheter, days 0, 1  
    L-ASP   6000 IU/m2 × 8 doses, 3 times weekly  
    ITT   Intrathecal triple therapy (methotrexate 7.5 mg; hydrocortisone 7.5 mg; ARA-C 15 mg), days 0, 7, 14, 21, 28  
    MTX   4 g/m2, days 21, 28  
    CF rescue   10 mg/m2 orally or intravenously every 6 h × ≥ 5 doses, start 18 h after MTX completion  
    VCR   0.05 mg/kg intravenous push  
Intensification, 4 wk  
    VP-16   100 mg/m2, days 36-40  
    DXM   10 mg/m2 orally 3 times daily, days 0-20, no taper  
    CPM   300 mg/m2/day intravenously, days 36-40  
Reinduction, 4 wk  
    CPM   250 mg/m2 every 12 h × 4 doses, days 2, 3  
    VCR   0.05 mg/kg days 0, 14; 0.03 mg/kg day 7  
    DNM   45 mg/m2/d × 2 days  
    DXM   10 mg/m2 divided 3 times daily, days 0-20, no taper  
    L-ASP   6000 IU/m2 intramuscularly × 8 doses, 3 times daily, days 0-20  
    ITT   Days 0, 14  
BMT for 11q23/MLL   
Reintensification, 6 wk  
    VCR   0.75 mg/m2 intravenously, days 0, 7  
    VHMTX   6000 mg/m2 in 1 h, followed by 1200 mg/m2/h × 23 hours × 2 doses, days 0, 14  
    CF rescue   200 mg/m2 intravenously over 1 h, then 12 mg/m2 intravenous push every 3 h × 6 doses, then 12 mg/m2 intravenously or orally every 6 h until plasma MTX level < 0.1 μM; start 12 h following MTX completion (36 h after start)  
    VP-16   100 mg/m2/d intravenously, days 28-32  
    CPM   300 mg/m2/d intravenously over 30 min, days 28-32  
    IT ARA-C   15 mg intrathecally, days 7, 21  
Consolidation, 9 wk  
    VHMTX   6000 mg/m2 intravenously in 1 h, followed by 1200 mg/m2/h intravenously for 23 h, days 28, 42  
    CF rescue   10 mg/m2 orally or intravenously every 6 h × ≥ 5 doses, start 18 h after MTX completion  
    IT ARA-C   15 mg intrathecally, days 35, 49  
    VCR   0.75 mg/m2 intravenously, days 28, 42  
    IV ARA-C   3000 mg/m2 intravenous 3 h infusion every 12 h, days 0, 2, 7, 8 for total of 8 doses  
    l-ASP   6000 IU/m2 intramuscularly 3 h after intravenous ARA-C on days 1, 8  
Intensified maintenance, 72 d × 3  
    VCR   0.75 mg/m2 intravenously, days 0, 28  
    DXM   10 mg/m2 divided orally 3 times daily, days 1-4 and 28-32  
    6-MP   75 mg/m2 orally, days 0-48  
    MTX   20 mg/m2 intramuscularly every week, days 0, 7, 14, 21, 28, 35, 42  
    VP-16   100 mg/m2/d, days 49-53  
    CPM   300 mg/m2/d intravenously over 30 min, days 49-53  
    IT ARA-C   15 mg intrathecally, days 0, 28  
Routine maintenance, 4 cycles, 1 y  
    VCR   1.5 mg/m2 intravenously every 4 wk × 12 doses, days 0, 28, 56  
    PRED   40 mg/m2 orally divided in 3 doses for 5 d with each VCR dose  
    MTX   20 mg/m2 orally weekly, days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77  
    6-MP   75 mg/m2 orally daily for 12 weeks per cycle  
    IT MTX
 
8 mg age 12-23 mo, 10 mg age 24-35 mo, day 0
 

Phase

Treatment regimen
Induction, 4 wk  
    CPM   250 mg/m2 every 12 h × 4 doses, days 2, 3  
    DXM   10 mg/m2 orally 3 times daily, days 0-20, no taper  
    VCR   0.05 mg/kg, days 0, 14; 0.03 mg/kg day 7  
    DNM   2 mg/kg/dose intravenously over 30 min for patients age ≤ 90 d  
  2 mg/kg/d; 4 mg/kg over 48 h, age > 90 d to < 6 mo  
  2.5 mg/kg/d; 5 mg/kg over 48 h, age 6 to < 9 mo  
  3 mg/kg/d; 6 mg/kg over 48 h, age ≥ 9 mo, as a 48-h continuous infusion through central venous catheter, days 0, 1  
    L-ASP   6000 IU/m2 × 8 doses, 3 times weekly  
    ITT   Intrathecal triple therapy (methotrexate 7.5 mg; hydrocortisone 7.5 mg; ARA-C 15 mg), days 0, 7, 14, 21, 28  
    MTX   4 g/m2, days 21, 28  
    CF rescue   10 mg/m2 orally or intravenously every 6 h × ≥ 5 doses, start 18 h after MTX completion  
    VCR   0.05 mg/kg intravenous push  
Intensification, 4 wk  
    VP-16   100 mg/m2, days 36-40  
    DXM   10 mg/m2 orally 3 times daily, days 0-20, no taper  
    CPM   300 mg/m2/day intravenously, days 36-40  
Reinduction, 4 wk  
    CPM   250 mg/m2 every 12 h × 4 doses, days 2, 3  
    VCR   0.05 mg/kg days 0, 14; 0.03 mg/kg day 7  
    DNM   45 mg/m2/d × 2 days  
    DXM   10 mg/m2 divided 3 times daily, days 0-20, no taper  
    L-ASP   6000 IU/m2 intramuscularly × 8 doses, 3 times daily, days 0-20  
    ITT   Days 0, 14  
BMT for 11q23/MLL   
Reintensification, 6 wk  
    VCR   0.75 mg/m2 intravenously, days 0, 7  
    VHMTX   6000 mg/m2 in 1 h, followed by 1200 mg/m2/h × 23 hours × 2 doses, days 0, 14  
    CF rescue   200 mg/m2 intravenously over 1 h, then 12 mg/m2 intravenous push every 3 h × 6 doses, then 12 mg/m2 intravenously or orally every 6 h until plasma MTX level < 0.1 μM; start 12 h following MTX completion (36 h after start)  
    VP-16   100 mg/m2/d intravenously, days 28-32  
    CPM   300 mg/m2/d intravenously over 30 min, days 28-32  
    IT ARA-C   15 mg intrathecally, days 7, 21  
Consolidation, 9 wk  
    VHMTX   6000 mg/m2 intravenously in 1 h, followed by 1200 mg/m2/h intravenously for 23 h, days 28, 42  
    CF rescue   10 mg/m2 orally or intravenously every 6 h × ≥ 5 doses, start 18 h after MTX completion  
    IT ARA-C   15 mg intrathecally, days 35, 49  
    VCR   0.75 mg/m2 intravenously, days 28, 42  
    IV ARA-C   3000 mg/m2 intravenous 3 h infusion every 12 h, days 0, 2, 7, 8 for total of 8 doses  
    l-ASP   6000 IU/m2 intramuscularly 3 h after intravenous ARA-C on days 1, 8  
Intensified maintenance, 72 d × 3  
    VCR   0.75 mg/m2 intravenously, days 0, 28  
    DXM   10 mg/m2 divided orally 3 times daily, days 1-4 and 28-32  
    6-MP   75 mg/m2 orally, days 0-48  
    MTX   20 mg/m2 intramuscularly every week, days 0, 7, 14, 21, 28, 35, 42  
    VP-16   100 mg/m2/d, days 49-53  
    CPM   300 mg/m2/d intravenously over 30 min, days 49-53  
    IT ARA-C   15 mg intrathecally, days 0, 28  
Routine maintenance, 4 cycles, 1 y  
    VCR   1.5 mg/m2 intravenously every 4 wk × 12 doses, days 0, 28, 56  
    PRED   40 mg/m2 orally divided in 3 doses for 5 d with each VCR dose  
    MTX   20 mg/m2 orally weekly, days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77  
    6-MP   75 mg/m2 orally daily for 12 weeks per cycle  
    IT MTX
 
8 mg age 12-23 mo, 10 mg age 24-35 mo, day 0
 

CPM indicates cyclophosphamide; DXM, dexamethasone; VCR, vincristine; DNM, daunomycin; l-ASP, l-asparaginase; ITT, intrathecal triple therapy (methotrexate; hydrocortisone; ARA-C); BMT, bone marrow transplantation; ARA-C, cytosine arabinoside; MTX, methotrexate; CF, citrovorum factor (leucovorin); VP-16, etoposide; VHMTX, very high dose methotrexate; IT, intrathecal; IV, intravenous; 6-MP, mercaptopurine; and PRED, prednisone.

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