AML protocols included in this study
| Protocol No. . | Phase . | Induction . | Consolidation . | Maintenance . | LP . | Guidance for CNS therapy . | Final accrual (patients included) . | Years . |
|---|---|---|---|---|---|---|---|---|
| E147914 | 3 | 1-2 courses of daunorubicin 60 mg/m2 per day on days 1-3; cytosine arabinoside continuous IV 200 mg/m2 per day on days 1-5; 6-thioguanine by mouth 100 mg/m2per day × 2 on days 1-5 (DAT) | Random assignment to consolidation × 2 plus maintenance or direct maintenance. Consolidation course: daunorubicin 45 mg/m2 on days 1-2; cytosine arabinoside IV push 100 mg/m2; 6-thioguanine oral 100 mg/m2 per day × 2 on days 1-5 | 6-thioguanine by mouth 40 mg/m2 per day × 2 for 4 days; cytosine arabinoside SC 60 mg/m2 on day 5; 2 years’ duration | Optional; strongly recommended if blast count is high | Methotrexate IT 10-15 mg every other day until clearance; whole brain RT optional. | 318 (289) | 1980-1982 |
| E348018 | 3 | 1-2 courses of full DAT or attenuated-dose DAT; daunorubicin 50 mg/m2 per day on day 1, cytosine arabinoside SC 100 mg/m2per day × 2 on days 1-5, and 6-thioguanine by mouth 100 mg/m2 per day × 2 on days 1-5 | 6-thioguanine by mouth 40 mg/m2 per day × 2 for 4 days; cytosine arabinoside SC 60 mg/m2 on day 5; 2 years’ duration | Optional; strongly recommended if blast count is high | Induction: methotrexate IT 10-15 mg every third day until clearance. Whole brain RT optional. Consolidation: investigator choice. Recommended: methotrexate IT once per week × 4, then IT once per month | 45 (39) | 1981-1982 | |
| E348315 | 3 | 1-2 courses of DAT | Age younger than 41 years + HLA-matched sibling allo-BMT. Others were randomly assigned to observation, maintenance, or consolidation × 1. After interim analysis, the observation arm was closed. Consolidation: cytosine arabinoside IV 3 g/m2 over 1 hour per day × 2 on days 1-6; amsacrine IV 100 mg/m2 per day on days 7-9 | 6-thioguanine by mouth 40 mg/m2 per day × 2 for 4 days; cytosine arabinoside SC 60 mg/m2 on day 5; 2 years’ duration | Mandatory | Induction: methotrexate IT once every 3 days. Consolidation: high-dose cytarabine or HSCT, if the patient was randomly assigned to maintenance-only cranial RT | 534 (445) | 1984-1988 |
| PC48616 | 2 | 1-2 courses of DAT | Age younger than 41 years and HLA-identical sibling allo-BMT; all others auto-BMT | Mandatory | Mitoxantrone IT 10-15 mg every third day until clearance and 2 doses thereafter; (patients with leukemic meningitis will not be eligible for autologous transplant) | 123 (98) | 1987-1990 | |
| E348917 | 3 | 1-2 courses of idarubicin 12 mg/m2 per day on days 1-3 and cytosine arabinoside continuous IV 100 mg/m2 per day on days 1-7 | Idarubicin 12 mg/m2 per day on days 1-2, and cytosine arabinoside continuous IV 100 mg/m2 per day on days 1-5. Patients with an HLA-matched or single- mismatched family member, allo-BMT; all others were randomly assigned to auto-BMT or 1 course of cytosine arabinoside IV 3 g/m2 over 1 hour per day × 2 on days 1-6 | Mandatory | Off study | 808 (752) | 1990-1995 | |
| E149019 | 3 | 1-2 courses of daunorubicin 60 mg/m2 per day on days 1-3; cytosine arabinoside continuous IV 100 mg/m2 per day on days 1-7 plus GM-CSF or placebo from day 11 | A single course of cytosine arabinoside IV 1.5 g/m2 over 1 hour per day × 2 on days 1-6 plus GM-CSF or placebo from day 11 | Mandatory | Induction: methotrexate IT 10-15 mg every third day until clearance and 2 doses thereafter; Consolidation: high-dose cytarabine | 124 (115) | 1990-1992 | |
| E399320 | 3 | GM-CSF or placebo as priming, cytosine arabinoside continuous IV 100 mg/m2 per day on days 1-7. Patients were randomly assigned to daunorubicin 45 mg/m2 per day on days 1-3 or mitoxantrone 12 mg/m2 per day on days 1-3 or idarubicin 12 mg/m2 per day on days 1-3 | Age younger than 70 years, cytosine arabinoside IV 1.5 g/m2 over 1 hour per day × 2 on days 1-6 plus GM-CSF from day 5. Age older than 70 years, cytosine arabinoside IV 1.5 g/m2 over 1 hour per day × 2 on days 1-3 plus GM-CSF from day 5 | Mandatory | Induction: methotrexate IT once every 3 days. Consolidation: high-dose cytarabine. If the patient was CSF positive after consolidation, methotrexate IT plus cranial RT | 362 (343) | 1993-1997 | |
| E499529 | 2 | 2 cycles of daunorubicin 45 mg/m2 per day on days 1-3, cytosine arabinoside continuous IV 100 mg/m2 per day on days 1-7, and cytosine arabinoside 2 g/m2 over 75-90 minutes per day × 2 on days 8-10 | Age younger than 51 years plus HLA-matched sibling, allo-PBSCT. Others, 2 courses of cytosine arabinoside 3 g/m2 over 3 hours per day × 2 on days 1, 3, and 5 and then auto-PBSCT | Only for CNS symptoms | Not mentioned (maybe because every patient received high-dose cytarabine) | 66 (59) | 1996-1997 | |
| E399721 | 2 | Daunorubicin 45 mg/m2 per day on days 1-3, cytosine arabinoside continuous IV 100 mg/m2 per day on days 1-7, and cytosine arabinoside 2 g/m2 over 60-90 minutes per day × 2 on days 8-10 plus rhIL-11 and GM-CSF from days 11 to 12 | 2 courses of cytosine arabinoside 3 g/m2 over 3 hours per day × 2 on days 1, 3, and 5 plus rhIL-11 and GM-CSF from day 6 | Only for CNS symptoms | Because patients received high-dose cytarabine in the induction, additional treatment is not necessary. It is possible to give methotrexate IT once every 3 days | 36 (35) | 1998-1999 | |
| E399922 | 3 | 1-2 courses of daunorubicin 45 mg/m2 per day on days 1-3, cytosine arabinoside continuous IV 100 mg/m2 per day on days 1-7, and zosuquidar or placebo | Cytosine arabinoside 1.5 g/m2 over 1 hour on days 1-6. Age younger than 70 years, per day × 2; age older than 70 years, per day × 1 (a course identical to the induction regimen that included either zosuquidar or placebo) | Only for clinical suspicion | Not mentioned | 449 (421) | 2002-2005 | |
| E190023 | 3 | Daunorubicin 45 or 90 mg/m2 per day on days 1-3, cytosine arabinoside continuous IV 100 mg/m2 per day on days 1-7 | Unfavorable or intermediate risk cytogenetic profile or WBC >100 × 103/μL at diagnosis plus HLA-matched sibling, allo-HSCT. All others: 2 courses of cytosine arabinoside 3 g/m2 over 3 hours per day × 2 on days 1, 3, and 5. Randomly assigned patients received gemtuzumab ozogamicin 6 mg/m2 or no gemtuzumab ozogamicin, and auto-HSCT | Only in patients with FAB M4/M5 with CNS signs and symptoms | Methotrexate IT 12 mg twice per week until clearance and then once per month for 6 months; alternative: cytosine arabinoside IT 30 mg | 657 (644) | 2002-2008 |
| Protocol No. . | Phase . | Induction . | Consolidation . | Maintenance . | LP . | Guidance for CNS therapy . | Final accrual (patients included) . | Years . |
|---|---|---|---|---|---|---|---|---|
| E147914 | 3 | 1-2 courses of daunorubicin 60 mg/m2 per day on days 1-3; cytosine arabinoside continuous IV 200 mg/m2 per day on days 1-5; 6-thioguanine by mouth 100 mg/m2per day × 2 on days 1-5 (DAT) | Random assignment to consolidation × 2 plus maintenance or direct maintenance. Consolidation course: daunorubicin 45 mg/m2 on days 1-2; cytosine arabinoside IV push 100 mg/m2; 6-thioguanine oral 100 mg/m2 per day × 2 on days 1-5 | 6-thioguanine by mouth 40 mg/m2 per day × 2 for 4 days; cytosine arabinoside SC 60 mg/m2 on day 5; 2 years’ duration | Optional; strongly recommended if blast count is high | Methotrexate IT 10-15 mg every other day until clearance; whole brain RT optional. | 318 (289) | 1980-1982 |
| E348018 | 3 | 1-2 courses of full DAT or attenuated-dose DAT; daunorubicin 50 mg/m2 per day on day 1, cytosine arabinoside SC 100 mg/m2per day × 2 on days 1-5, and 6-thioguanine by mouth 100 mg/m2 per day × 2 on days 1-5 | 6-thioguanine by mouth 40 mg/m2 per day × 2 for 4 days; cytosine arabinoside SC 60 mg/m2 on day 5; 2 years’ duration | Optional; strongly recommended if blast count is high | Induction: methotrexate IT 10-15 mg every third day until clearance. Whole brain RT optional. Consolidation: investigator choice. Recommended: methotrexate IT once per week × 4, then IT once per month | 45 (39) | 1981-1982 | |
| E348315 | 3 | 1-2 courses of DAT | Age younger than 41 years + HLA-matched sibling allo-BMT. Others were randomly assigned to observation, maintenance, or consolidation × 1. After interim analysis, the observation arm was closed. Consolidation: cytosine arabinoside IV 3 g/m2 over 1 hour per day × 2 on days 1-6; amsacrine IV 100 mg/m2 per day on days 7-9 | 6-thioguanine by mouth 40 mg/m2 per day × 2 for 4 days; cytosine arabinoside SC 60 mg/m2 on day 5; 2 years’ duration | Mandatory | Induction: methotrexate IT once every 3 days. Consolidation: high-dose cytarabine or HSCT, if the patient was randomly assigned to maintenance-only cranial RT | 534 (445) | 1984-1988 |
| PC48616 | 2 | 1-2 courses of DAT | Age younger than 41 years and HLA-identical sibling allo-BMT; all others auto-BMT | Mandatory | Mitoxantrone IT 10-15 mg every third day until clearance and 2 doses thereafter; (patients with leukemic meningitis will not be eligible for autologous transplant) | 123 (98) | 1987-1990 | |
| E348917 | 3 | 1-2 courses of idarubicin 12 mg/m2 per day on days 1-3 and cytosine arabinoside continuous IV 100 mg/m2 per day on days 1-7 | Idarubicin 12 mg/m2 per day on days 1-2, and cytosine arabinoside continuous IV 100 mg/m2 per day on days 1-5. Patients with an HLA-matched or single- mismatched family member, allo-BMT; all others were randomly assigned to auto-BMT or 1 course of cytosine arabinoside IV 3 g/m2 over 1 hour per day × 2 on days 1-6 | Mandatory | Off study | 808 (752) | 1990-1995 | |
| E149019 | 3 | 1-2 courses of daunorubicin 60 mg/m2 per day on days 1-3; cytosine arabinoside continuous IV 100 mg/m2 per day on days 1-7 plus GM-CSF or placebo from day 11 | A single course of cytosine arabinoside IV 1.5 g/m2 over 1 hour per day × 2 on days 1-6 plus GM-CSF or placebo from day 11 | Mandatory | Induction: methotrexate IT 10-15 mg every third day until clearance and 2 doses thereafter; Consolidation: high-dose cytarabine | 124 (115) | 1990-1992 | |
| E399320 | 3 | GM-CSF or placebo as priming, cytosine arabinoside continuous IV 100 mg/m2 per day on days 1-7. Patients were randomly assigned to daunorubicin 45 mg/m2 per day on days 1-3 or mitoxantrone 12 mg/m2 per day on days 1-3 or idarubicin 12 mg/m2 per day on days 1-3 | Age younger than 70 years, cytosine arabinoside IV 1.5 g/m2 over 1 hour per day × 2 on days 1-6 plus GM-CSF from day 5. Age older than 70 years, cytosine arabinoside IV 1.5 g/m2 over 1 hour per day × 2 on days 1-3 plus GM-CSF from day 5 | Mandatory | Induction: methotrexate IT once every 3 days. Consolidation: high-dose cytarabine. If the patient was CSF positive after consolidation, methotrexate IT plus cranial RT | 362 (343) | 1993-1997 | |
| E499529 | 2 | 2 cycles of daunorubicin 45 mg/m2 per day on days 1-3, cytosine arabinoside continuous IV 100 mg/m2 per day on days 1-7, and cytosine arabinoside 2 g/m2 over 75-90 minutes per day × 2 on days 8-10 | Age younger than 51 years plus HLA-matched sibling, allo-PBSCT. Others, 2 courses of cytosine arabinoside 3 g/m2 over 3 hours per day × 2 on days 1, 3, and 5 and then auto-PBSCT | Only for CNS symptoms | Not mentioned (maybe because every patient received high-dose cytarabine) | 66 (59) | 1996-1997 | |
| E399721 | 2 | Daunorubicin 45 mg/m2 per day on days 1-3, cytosine arabinoside continuous IV 100 mg/m2 per day on days 1-7, and cytosine arabinoside 2 g/m2 over 60-90 minutes per day × 2 on days 8-10 plus rhIL-11 and GM-CSF from days 11 to 12 | 2 courses of cytosine arabinoside 3 g/m2 over 3 hours per day × 2 on days 1, 3, and 5 plus rhIL-11 and GM-CSF from day 6 | Only for CNS symptoms | Because patients received high-dose cytarabine in the induction, additional treatment is not necessary. It is possible to give methotrexate IT once every 3 days | 36 (35) | 1998-1999 | |
| E399922 | 3 | 1-2 courses of daunorubicin 45 mg/m2 per day on days 1-3, cytosine arabinoside continuous IV 100 mg/m2 per day on days 1-7, and zosuquidar or placebo | Cytosine arabinoside 1.5 g/m2 over 1 hour on days 1-6. Age younger than 70 years, per day × 2; age older than 70 years, per day × 1 (a course identical to the induction regimen that included either zosuquidar or placebo) | Only for clinical suspicion | Not mentioned | 449 (421) | 2002-2005 | |
| E190023 | 3 | Daunorubicin 45 or 90 mg/m2 per day on days 1-3, cytosine arabinoside continuous IV 100 mg/m2 per day on days 1-7 | Unfavorable or intermediate risk cytogenetic profile or WBC >100 × 103/μL at diagnosis plus HLA-matched sibling, allo-HSCT. All others: 2 courses of cytosine arabinoside 3 g/m2 over 3 hours per day × 2 on days 1, 3, and 5. Randomly assigned patients received gemtuzumab ozogamicin 6 mg/m2 or no gemtuzumab ozogamicin, and auto-HSCT | Only in patients with FAB M4/M5 with CNS signs and symptoms | Methotrexate IT 12 mg twice per week until clearance and then once per month for 6 months; alternative: cytosine arabinoside IT 30 mg | 657 (644) | 2002-2008 |
allo, allogeneic; auto, autologous; BMT, bone marrow transplantation; DAT, daunorubicin, low-dose cytosine arabinoside, and 6-thioguanine; GM-CSF, granulocyte-macrophage colony-stimulating factor; HSCT, hematopoietic stem cell transplantation; IT, intrathecal; IV, intravenous; PBSCT, peripheral blood stem cell transplantation; rhIL-11, recombinant human interleukin-11; RT, radiotherapy; SC, subcutaneous.