At entry patients were randomised to any, or all, of three treatment comparisons: ADE versus FLA; G CSF versus not and ATRA versus not. Patients received 2 courses of their allocated therapy. Patients who were then in complete remission after 2 courses received consolidation with either high dose Ara C or transplantation.
The AMLHR closed in 2003 with 406 patients randomised.
The Intensive treatment arm compared two doses of Daunorubicin (50 mg/m2 vs 35 mg/m2), two doses of Cytosine Arabinoside (200 mg/m2 vs 400 mg/m2), and three versus four courses of treatment in total. The Non-Intensive treatment arm compared scheduled Low Dose Cytosine Arabinoside versus scheduled Low Dose Cytosine Arabinoside plus the immunoconjugate Gemtuzumab Ozogamicin (GO).
The non-intensive randomisation closed to recruitment in 2006 with 321 patients in total, and the intensive arm closed in 2005 with 1273 participants.
Through the use of an efficient factorial design, AML15 evaluated several relevant therapeutic questions in AML. For patients who did not have the Acute Promyelocytic (APL) subtype, an induction randomisation compared the standard ADE and DA regimens. Patients who had a FLT3 mutation at diagnosis were randomised to combine, or not, a FLT3 inhibitor after each course of the allocated induction and consolidation chemotherapy. A consolidation randomisation compared MRC chemotherapy (MACE + MidAC) with high-dose Ara-C. The 4 versus 5 courses randomisation from AML12 continued in patients under 45 years, but the fifth course was Ara-C. The role of the immunoconjugate Mylotarg was evaluated in consolidation (course 3) in patients who did not enter the FLT3 inhibitor randomisation. The role of allogeneic transplant, either standard or “mini”, was assessed in standard and poor risk patients.
The AML15 trial closed in 2009 with 3484 patients randomised from 162 centres.
The intensive approach compared two standard chemotherapy schedules DA (Daunorubicin/Ara-C) with ADE (Daunorubicin/Ara- C/Etoposide). In addition, the role of all-trans-retinoic Acid (ATRA) in combination with these treatments in the first induction course was evaluated. Patients who achieved complete remission (CR) or partial remission (PR) after course one received a second course of the same treatment with the ATRA if allocated to do so, and were then randomised to one further course or not and were be eligible for a non-intensive allogeneic stem cell transplant if a suitable HLA matched donor was available. Patients who failed to achieve a CR or PR after course 1 and were in CR after course 2 received course 3. Patients who didn’t have a donor were randomised to maintenance with Azacytidine or not.
Patients who were not considered fit for an intensive treatment approach were randomised between an established approach to non-intensive treatment, namely Low Dose Ara-C versus one of two novel treatments, which are Low Dose Clofarabine or Sapacitabine.
The non-intensive randomisation closed to recruitment in 2011 with 902 patients in total, and the intensive arm closed in 2012 with 1881 participants.