Acute Myeloid Leukaemia Trial 15 (AML 15)

Lead Research Organisation: University of Wales
Department Name: UNLISTED

Abstract

The cure rate of patients with AML under 60 years is improving as a result of increasing intensity of treatment (1980 - 12%: 2000-53%). In this trial two induction combinations (H-DAT and FLAG-Ida) will be compared. H-DAT was the better arm from the recent MRC Trial and FLAG-Ida is widely used but never compared in a randomised trial. The trial will try to refine treatment to prevent relapse. The best chemotherapy arm of the current MRC trial will be compared with high dose Cytosine-Arabinoside (Ara-C) which is widely used in the USA. Two dose levels of Ara-C will be tested. It is not clear how many total courses of treatment are needed. This trial will compare 4 vs 5 courses and will add to the experience of the 4 vs 5 course comparison from the present AML12 trial. A new agent which is a drug attached to an antibody to specifically target leukaemia cells has recently been developed. This trial will assess the value of adding this immunoconjugate to both induction and/or consolidation treatment.

About 15% of cases are Acute Promyelocytic Leukaemia. It may be possible to cure a high proportion of cases (~80%) as done in the current AML12 trial, but with much less intensive chemotherapy developed by the Spanish Group. We will compare the MRC versus the Spanish approach. We anticipate a recruitment of 550 patients <60 years per annum from 200 centres in the UK.

Technical Summary

This is a major randomised trial in Acute Myeloid Leukaemia in patients under 60 years old to be conducted in 200 institutions in the UK and several abroad. In induction phase H-DAT (derived from the current MRC AML12 Trial) will be compared with FLAG-Ida which has never been subjected to randomised comparison. In addition the value of immunoconjugate (CMA676/Myelotarg - a humanised anti CD33 linked to Calicheamycin) given or not on day 1 of treatment. High risk patients will leave the trial and enter the MRC AML-HR trial. In consolidation patients who have a matched donor will receive a transplant as course 3. Patients <35 years will receive a conventional allograft. In patients 35-45 will have a choice of a conventional allograft or a non-ablative minigraft: patients over 45 will receive a minigraft. Only standard risk patients will be transplanted. The value of a transplant will be compared with 4 or 5 courses of chemotherapy on a donor versus no donor analysis. Patients not allocated to transplant will enter a comparison of MRC consolidation (MACE + MidAc) versus high dose Ara-C. In addition 2 doses of Ara-C (3g vs 1?g) will be compared. With each course of consolidation chemotherapy patients will be randomised to receive immunoconjugate (CMA-676/Myelotarg) or not. Finally patients who have completed 4 courses of chemotherapy will be randomised to receive a 5th course (1g Ara-C) or not.

Patients with the Acute Promyelocytic subgroup will enter a comparison of the established MRC approach with the Anthracycline based Spanish approach with economic and quality of life comparison.

Publications

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Burnett AK (2011) Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. in Journal of clinical oncology : official journal of the American Society of Clinical Oncology

 
Description Established as standard of care in the UK and Denmark
Geographic Reach Europe 
Policy Influence Type Citation in other policy documents
Impact Established as standard of care in the UK and Denmark
 
Description Open days and patient association 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Primary Audience Participants in your research and patient groups
Results and Impact Presented at open days and patient association

Improved knowledge of Leukaemia trials activity and research amongst patients, carers and general public.
Year(s) Of Engagement Activity 2009