Condition category
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

Contact information



Primary contact

Prof AK Burnett


Contact details

Department of Haematology
University of Wales College of Medicine
Heath Park
CF14 4XN
United Kingdom
+44 (0)29 2074 2375

Additional identifiers

EudraCT number

2005-001149-40 number

Protocol/serial number


Study information

Scientific title



Study hypothesis

The AML trial has two separate parts:
1. For patients with Acute Myeloid Leukaemia (AML), other than acute promyelocytic leukaemia (APL), as defined by the World Health Organisation (WHO) classification (2001).
2. For patients with Acute Promyelocytic Leukaemia (APL).
The objectives for each of these components are summarised below.

Therapeutic questions for patients with non-APL AML: For patients with acute myeloid leukaemia (AML) the aims of the AML15 trial are:
1. To compare two induction schedules (namely DAT and FLAG-Ida)
2. To assess the value of Mylotarg during induction
3. To compare the standard MRC consolidation chemotherapy (i.e. MACE + MidAC) versus high-dose Ara-C
4. For those allocated to high-dose Ara-C to compare high-dose ARA-C during consolidation (see above) at two different doses (1.5 g/m squared versus 3.0g/m squared)
5. To assess the value of Mylotarg during consolidation
6. To compare four versus five courses of treatment in total (where the final course is intermediate-dose Ara-C)
7. In standard and poor risk patients, to evaluate, by means of a genetic randomisation, the value of allogeneic stem cell transplantation [SCT, whether standard allogeneic (allo-SCT) or non-myeloablative ‘mini’ allogeneic (mini-SCT)]

Therapeutic questions for patients with APL. For patients with APL:
1. To compare the MRC approach (i.e. four courses of intensive chemotherapy) with the Spanish approach (based on anthracyclines with maintenance therapy)
2. To assess the value of Mylotarg during consolidation (i.e. with course 3)

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Not Specified

Patient information sheet




1. (R1) Patients with acute promyelocytic leukemia (APL) will be randomised to receive oral retinoic acid together with either MRC H-DAT chemotherapy or the Spanish Intermittent Idarubicin. Following confirmation of remission, patients will continue with the MRC (DAT:MACE:MIDAC) or Spanish chemotherapy but will be randomised to receive CMA-676/Myelotarg (Immunoconjugate) on day 1 of course 3 or not. (Patients will be monitered molecularly by Reverse Transcription (RT) and real time Polymerase Chain Reaction (PCR) to predict relapse. Three quality of life assessments will be made at 3, 6 and 9 months and resource use information will be collected for cost benefit analysis.)
2. (R2) Non-APL patients will be randomised to receive induction cources 1 and 2 with H-Dat (Daunorbicin:Ara-C, Thioguanine) or FLA_G IDA (Fludarabine, Ara C, G-CSF, Idarubicin) and to receive CMA-676 (Myelotarg) on day 1 of course 1 or not.
3. Following the first course of chemotherapy the risk profile of each patient will be determined (based on cytogenetics, blast clearance after course 1). Good risk patients (15%) will leave AML15 and will enter the MRC AML High Risk Trial.
4. (R3)(R4) Patients who have completed course 2 and are allocated to the chemotherapy comparisons will be randomised to receive CMA-676 (Myelotarg) on day 1 of course 3.
5. (R5) All patients allocated to allogenic transplant up to 35 years will receive standard conditioning (Cyclophosphamide/TBI) with stem cells obtained from peripheral blood or bone marrow as course 3. For patients 36-50 investigators may choose a conventional transplant or a non-ablative transplant. Patients over 50 years will receive a non-ablative transplant. The non-ablative transplant will be given as course 4, ie patients will receive MACE as course 3 before proceeding to transplant.
7. Patients who relapse at any point in the trial will be entered into the MRC AML HR Trial.

Intervention type



Not Specified

Drug names

Primary outcome measure

The main endpoints for each comparison will be:
1. Complete remission (CR) achievement and reasons for failure (for induction questions)
2. Duration of remission, relapse rates and deaths in first CR
3. Overall survival
4. Toxicity, both haematological and non-haematological, and quality of life
5. Supportive care requirements (and other aspects of health economics)

Secondary outcome measures

Not provided at time of registration

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Any form of de novo or secondary AML
2. Suitable for intensive chemotherapy
3. Under 60 years
4. Written consent

Participant type


Age group

Not Specified


Not Specified

Target number of participants


Participant exclusion criteria

1. Previous chemotherapy for AML
2. Blast transferration of CML
3. Pregnant or lactating
4. Abnormal liver function tests for Mylotarg randomisations

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Department of Haematology
CF14 4XN
United Kingdom

Sponsor information


Cardiff University (UK)

Sponsor details

CF10 3XQ
United Kingdom
+44 (0)29 2087 4000

Sponsor type




Funder type

Research council

Funder name

Medical Research Council (MRC) (UK)

Alternative name(s)


Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government


United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

2003 results of a feasibility study in:
2010 results in:
2010 pooled analysis of prognostic significance of rare recurring chromosomal abnormalities in: (see also ISRCTN55678797)
2012 results in:
2013 results in:
2013 results in:
2014 results in:

Publication citations

  1. Results of a feasibility study

    Kell WJ, Burnett AK, Chopra R, Yin JA, Clark RE, Rohatiner A, Culligan D, Hunter A, Prentice AG, Milligan DW, A feasibility study of simultaneous administration of gemtuzumab ozogamicin with intensive chemotherapy in induction and consolidation in younger patients with acute myeloid leukemia., Blood, 2003, 102, 13, 4277-4283, doi: 10.1182/blood-2003-05-1620.

  2. Results

    Burnett AK, Hills RK, Green C, Jenkinson S, Koo K, Patel Y, Guy C, Gilkes A, Milligan DW, Goldstone AH, Prentice AG, Wheatley K, Linch DC, Gale RE, The impact on outcome of the addition of all-trans retinoic acid to intensive chemotherapy in younger patients with nonacute promyelocytic acute myeloid leukemia: overall results and results in genotypic subgroups defined by mutations in NPM1, FLT3, and CEBPA., Blood, 2010, 115, 5, 948-956, doi: 10.1182/blood-2009-08-236588.

  3. Results

    Yin JA, O'Brien MA, Hills RK, Daly SB, Wheatley K, Burnett AK, Minimal residual disease monitoring by quantitative RT-PCR in core binding factor AML allows risk stratification and predicts relapse: results of the United Kingdom MRC AML-15 trial., Blood, 2012, 120, 14, 2826-2835, doi: 10.1182/blood-2012-06-435669.

  4. Results

    Burnett AK, Goldstone A, Hills RK, Milligan D, Prentice A, Yin J, Wheatley K, Hunter A, Russell N, Curability of patients with acute myeloid leukemia who did not undergo transplantation in first remission., J. Clin. Oncol., 2013, 31, 10, 1293-1301, doi: 10.1200/JCO.2011.40.5977.

  5. Results

    Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J, Gibson BE, Wheatley K, Milligan D, Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial., J. Clin. Oncol., 2013, 31, 27, 3360-3368, doi: 10.1200/JCO.2012.47.4874.

  6. Results

    Linch DC, Hills RK, Burnett AK, Khwaja A, Gale RE, Impact of FLT3(ITD) mutant allele level on relapse risk in intermediate-risk acute myeloid leukemia., Blood, 2014, 124, 2, 273-276, doi: 10.1182/blood-2014-02-554667.

  7. Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, Wheatley K, Harrison CJ, Burnett AK, , Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials., Blood, 2010, 116, 3, 354-365, doi: 10.1182/blood-2009-11-254441.

Additional files

Editorial Notes