A trial of directed therapy in younger patients with acute myeloid leukaemia: MRC AML 15

ISRCTN	ISRCTN17161961
DOI	https://doi.org/10.1186/ISRCTN17161961
EudraCT/CTIS number	2005-001149-40
Secondary identifying numbers	G9901427

Submission date: 02/05/2001
Registration date: 02/05/2001
Last edited: 24/03/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

http://cancerhelp.cancerresearchuk.org/trials/a-trial-comparing-different-chemotherapy-regimes-and-the-use-of-mylotarg-monoclonal-antibody-in-treatment-of-acute-myeloid-leukaemia

Study website

Contact information

Prof AK Burnett
Scientific

Department of Haematology
University of Wales College of Medicine
Heath Park
Cardiff
CF14 4XN
United Kingdom

Phone	+44 (0)29 2074 2375
Email	burnettak@cardiff.ac.uk

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Not Specified
Scientific title	A trial of directed therapy in younger patients with acute myeloid leukaemia: MRC AML 15
Study acronym	MRC AML 15
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(s)	Not provided at time of registration
Condition	Leukaemia
Intervention	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	Other
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 study start date	01/03/2002
Overall study end date	01/06/2008

Eligibility

Participant type(s)	Patient
Age group	Not Specified
Sex	Not Specified
Target number of participants	3000
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 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	01/03/2002
Recruitment end date	01/06/2008

Locations

Countries of recruitment

United Kingdom
Wales

Study participating centre

Department of Haematology

Cardiff
CF14 4XN
United Kingdom

Sponsor information

Cardiff University (UK)
University/education

-
Cardiff
CF10 3XQ
Wales
United Kingdom

Phone	+44 (0)29 2087 4000
Email	abc@email.com
"ROR"	https://ror.org/03kk7td41

Funders

Funder type

Research council

Medical Research Council (MRC) (UK)
Government organisation / National government

Alternative name(s): Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results of a feasibility study	15/12/2003		Yes	No
Results article	results	04/02/2010		Yes	No
Other publications	pooled analysis of prognostic significance of rare recurring chromosomal abnormalities	22/07/2010		Yes	No
Results article	results	04/10/2012		Yes	No
Results article	results	01/04/2013		Yes	No
Results article	results	20/09/2013		Yes	No
Results article	results	10/07/2014		Yes	No
Results article	results	01/01/2018	25/07/2019	Yes	No
Plain English results		23/08/2013	29/10/2021	No	Yes
Plain English results			24/03/2022	No	Yes

Editorial Notes

24/03/2022: Plain English results added.
29/10/2021: The Cancer Research UK lay results summary has been added.
25/07/2019: Publication reference added.