Table 1.
Acute Myeloid Leukemia Protocols Included in the Analysis
| Protocol No. | Clinical Trial Phase | Induction | Consolidation | Maintenance | Activation-Termination Dates | Final Accrual (patients included) |
|---|---|---|---|---|---|---|
| E147911 | III | One or two courses of: dauno 60 mg/m2/d, days 1-3; ARA-C 25 mg/m2 IV push followed by continuous IV 200 mg/m2/d, days 1-5; and PO 6-TG 100 mg/m2 × 2/d, days 1-5 (DAT). | Randomly assigned to either: a) two courses of consolidation therapy followed by maintenance, or b) begin maintenance immediately. A consolidation course consisted of dauno 45 mg/m2, days 1 and 2; ARA-C 100 mg/m2 IV push; and PO 6-TG 100 mg/m2 × 2/d, days 1-5. | PO 6-TG 40 mg/m2 × 2/d, 4 days, followed by SC ARA-C 60 mg/m2 on the fifth day. Duration: 2 years. | Feb 1980 to Apr 1982 | 318 (289) |
| E348015 | III | One or two courses of either: a) full DAT (above), or b) attenuated-dose DAT: dauno 50 mg/m2/d on day 1, SC ARA-C 100 mg/m2 × 2/d, days 1-5 and PO 6-TG 100 mg/m2 × 2/d, days 1-5. | PO 6-TG 40 mg/m2 × 2/d, 4 days, followed by SC ARA-C 60 mg/m2 on the fifth day. Duration: 2 years. | Jul 1981 to Nov 1982 | 45 (39) | |
| E348312 | III | One or two courses of DAT. | Age < 41 years plus HLA-matched sibling: alloBMT. Others were initially randomly assigned to one of three arms: a) observation, b) maintenance, or c) one course of consolidation. After interim analysis, the observation arm was closed. Consolidation therapy: IV ARA-C, 3 g/m2 over 1 hour × 2/d, days 1-6, followed by IV amsacrine, 100 mg/m2/d, days 7-9. | PO 6-TG 40 mg/m2 × 2/d, for 4 days, followed by SC ARA-C 60 mg/m2 on the fifth day. Duration: 2 years. | Mar 1984 to Jan 1988 | 534 (445) |
| PC48613 | II | One or two courses of DAT. | Patients in CR: a) age < 41 years and HLA identical sibling: alloBMT, and b) all others: autoBMT. | Apr 1987 to Apr 1990 | 123 (98) | |
| E348914 | III | One or two courses of idarubicin 12 mg/m2/d, days 1-3; and ARA-C 25 mg/m2 IV push, followed by continuous IV 100 mg/m2/d, days 1-7. | Idarubicin 12 mg/m2/d, days 1 and 2; and ARA-C 25 mg/m2 IV push, followed by continuous IV 100 mg/m2/d, days 1-5. a) Patients with an HLA-matched or single-mismatched family member: alloBMT. All others were randomly assigned to b) autoBMT, or c) a single course of IV ARA-C 3 g/m2 over 3 hours × 2/d, days 1-6. | Feb 1990 to Feb 1995 | 808 (753) | |
| E149016 | III | One or two courses of dauno 60 mg/m2/d, days 1-3; ARA-C 25 mg/m2 IV push followed by continuous IV 100 mg/m2/d, days 1-7; plus GM-CSF v placebo from day 11. | A single course of IV ARA-C 1.5 g/m2 over 1 hour × 2/d, days 1-6, plus GM-CSF v placebo from day 11. | Sep 1990 to Nov 1992 | 124 (115) | |
| E399317 | III | GM-CSF v placebo as priming, ARA-C continuous IV 100 mg/m2/d, days 1-7. Patients were randomly assigned to receive either: a) dauno 45 mg/m2/d, days 1-3; b) mitox 12 mg/m2/d, days 1-3; or c) idarubicin 12 mg/m2/d, days 1-3. | Age < 70 years: IV ARA-C 1.5 g/m2 over 1 hour × 2/d, days 1-6, plus GM-CSF from day 5. Age > 70 years: IV ARA-C 1.5 g/m2 over 1 hour × 2/d, days 1-3, plus GM-CSF from day 5. | Apr 1993 to Feb 1997 | 362 (343) | |
| E499521 | II | Two cycles of: dauno 45 mg/m2/d, days 1-3; ARA-C continuous IV 100 mg/m2/d, days 1-7; and ARA-C 2 g/m2 over 75-90 min × 2/d, days 8-10. | Age < 51 years plus HLA-matched sibling: alloPBSCT. Others: two courses of ARA-C 3 g/m2 over 3 hours × 2/d, days 1, 3, 5, and then autoPBSCT. | Aug 1996 to Feb 1997 | 66 (59) | |
| E399718 | II | Dauno 45 mg/m2/d, days 1-3; ARA-C continuous IV 100 mg/m2/d, days 1-7; and ARA-C 2 g/m2 over 60-90 min x 2/d, days 8-10 plus rhIL-11 and GM-CSF from days 11 to 12. | Two courses of: ARA-C 3g/m2 over 3 hours × 2/d, days 1, 3, 5 plus rhIL-11 and GM-CSF from day 6. | Jun 1998 to Apr 1999 | 36 (35) | |
| E399919 | III | One or two courses of dauno 45 mg/m2/d, days 1-3; ARA-C continuous IV 100 mg/m2/d, days 1-7; and zosuquidar v placebo. | 1) ARA-C 1.5 g/m2 over 1 hour, days 1-6: age < 70 years, × 2/d; age > 70 years, × 1/d. 2) A course identical to the induction regimen, including either zosuquidar or placebo. | Jul 2002 to Sep 2005 | 449 (421) | |
| E190020 | III | Dauno 45 v 90 mg/m2/d, days 1-3; ARA-C continuous IV 100 mg/m2/d, days 1-7. | Unfavorable/intermediate risk cytogenetic profile or a WBC count > 100,000/μL at diagnosis plus HLA-matched sibling: alloHSCT. All others: 1) two courses of ARA-C 3 g/m2 over 3 hours × 2/d, days 1, 3, and 5; 2) random assignment: GO 6 mg/m2 v no GO; and 3) autoHSCT. | Dec 2002 to Nov 2008 | 657 (644) |
Abbreviations: allo, allogeneic; ARA-C, cytarabine; auto, autologous; BMT, bone marrow transplantation; CR, complete remission; d, day; DAT, daunorubicin plus ARA-C plus 6-TG; dauno, daunorubicin; GM-CSF, granulocyte-macrophage colony-stimulating factor; GO, gemtuzumab ozogamicin; HSCT, hematopoietic stem-cell transplantation; IV, intravenous; mitox, mitoxantrone; PBSCT, peripheral blood stem-cell transplantation; PO, orally; rhIL-11, recombinant human interleukin 11; SC, subcutaneous; 6-TG, thioguanine.