AML17: a programme of treatment development in younger patients with Acute Myeloid Leukaemia and high-risk myelodysplastic syndrome

ISRCTN	ISRCTN55675535
DOI	https://doi.org/10.1186/ISRCTN55675535
EudraCT/CTIS number	2007-003798-16
Secondary identifying numbers	CU 372-07

Submission date: 21/06/2007
Registration date: 02/07/2007
Last edited: 25/10/2022

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://www.cancerhelp.org.uk/trials/a-trial-looking-treatment-children-acute-myeloid-leukaemia-aml-17
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-acute-myeloid-leukaemia-aml-17
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-treatment-acute-promyelocytic-leukaemia-AML-17

Contact information

Prof Alan Burnett
Scientific

School of Medicine
Cardiff University
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)	Hospital
Study type	Treatment
Participant information sheet	Patient information material can be found at: http://AML17.cardiff.ac.uk
Scientific title	AML17: a programme of treatment development in younger patients with Acute Myeloid Leukaemia and high-risk myelodysplastic syndrome
Study acronym	AML17
Study hypothesis	Best chemotherapy +/- molecular intervention and risk-directed chemotherapy.
Ethics approval(s)	MREC for Wales, 08/10/2008, ref: 08/MRE09/29
Condition	Acute myeloid leukaemia/high-risk myelodysplastic syndrome
Intervention	Current interventions as of 24/06/2008: 1. In acute promyelocytic leukaemia (APL) patients to compare idarubicin and all-trans retinoic acid (ATRA) versus ATRA and arsenic 2. In non-APL patients to compare ara-C/dauno/etoposide (ADE) alone versus ADE or ara-C/dauno (DA) each with Mylotarg at two different doses (five arms): 2.1. ADE alone 2.2. ADE and Mylotarg (3 mg) 2.3. DA and Mylotarg (3 mg) 2.4. ADE and Mylotarg (6 mg) 2.5. DA and Mylotarg (6 mg) 3. Three versus four courses of total therapy 4. +/- CEP-701 (lestaurtinib) in FLT3 mutants 5. Dauno and clofarabine versus fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-Ida) in high-risk patients 6. +/- mTOR inhibition in non-CBF, non-FLT3 mutant, in non-high risk patients The treatment period is approximately 4 to 6 months. Previous interventions: 1. In acute promyelocytic leukaemia (APL) patients to compare idarubicin and all-trans retinoic acid (ATRA) versus ATRA and arsenic 2. In non-APL patients to compare ara-C/dauno/etoposide (ADE) alone versus ADE or ara-C/dauno (DA) each with Mylotarg at two different doses (five arms): 2.1. ADE alone 2.2. ADE and Mylotarg (3 mg) 2.3. DA and Mylotarg (3 mg) 2.4. ADE and Mylotarg (6 mg) 2.5. DA and Mylotarg (6 mg) 3. Three versus four courses of total therapy 4. +/- CEP-701 (lestaurtinib) in FLT3 mutants 5. Dauno and clofarabine versus dauno and cloretazine versus fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-Ida) in high-risk patients 6. +/- mTOR inhibition in non-CBF, non-FLT3 mutant, in non-high risk patients The treatment period is approximately 4 to 6 months.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Idarubicin, all-trans retinoic acid (ATRA), arsenic, ara-C/dauno/etoposide (ADE), ara-C/dauno (DA), mylotarg (gemtuzumab ozogamicin), lestaurtinib, clofarabine, cloretazine, fludarabine, cytarabine, granulocyte colony-stimulating factor
Primary outcome measure	1. Complete remission (CR), measured at approximately 1 month and if required approximately 6 weeks later i.e. after course 1 and/or 2 2. CR duration 3. Relapse rate, monitored over 5 years 4. Deaths in CR, monitored over 5 years 5. Overall survival (at 5 years) 6. Toxicity 7. Quality of life, measured at baseline and at 3, 6, 12 and 24 months for those in the APL section of the trial, and at 3, 6 and 12 months for patients in the minimal residual disease monitoring. The European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire for Cancer patients (EORTC QLQC-30) and Hospital Anxiety and Depression Score (HADS) will be used. 8. Supportive care requirements
Secondary outcome measures	1. Detection of minimal residual disease 2. Correlation of serum inhibitory activity
Overall study start date	01/09/2008
Overall study end date	31/12/2020

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	2700
Participant inclusion criteria	1. They have one of the forms of acute myeloid leukaemia (AML) as defined by the World Health Organization (WHO) 2. They are considered suitable for intensive chemotherapy 3. They are less than 60 years 4. For Mylotarg (gemtuzumab ozogamicin) intervention, have liver function tests within twice the upper limit of normal
Participant exclusion criteria	1. No previous cytotoxic therapy for AML other than hydroxyurea 2. Blast transformation of chronic myeloid leukaemia (CML) 3. Concurrent active malignancy 4. Pregnant or lactating 5. Children with Down's syndrome
Recruitment start date	01/09/2008
Recruitment end date	01/07/2014

Locations

Countries of recruitment

Denmark
United Kingdom
Wales

Study participating centre

Cardiff University

Cardiff
CF14 4XN
United Kingdom

Sponsor information

Cardiff University (UK)
University/education

c/o Dr Kathy Pittard-Davies
33-36 Newport Road
Cardiff
CF2
Wales
United Kingdom

Phone	+44 (0)29 2087 9274
Email	DaviesKP2@Cardiff.ac.uk
Website	http://www.Cardiff.ac.uk
"ROR"	https://ror.org/03kk7td41

Funders

Funder type

Research council

Cancer Research UK (CRUK) (UK)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

Genzyme Ltd (UK) - supplying clofarabine

No information available

Novartis Pharmaceuticals UK Limited (UK) - supplying mTOR inhibitor

No information available

Cephalon UK Ltd (UK) - providing arsenic trioxide and CEP-701

No information available

Bioenvision Ltd (UK) - providing clofarabine

No information available

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	18/06/2015		Yes	No
Results article	results	01/10/2015		Yes	No
Results article	results	04/02/2016		Yes	No
Results article	results	01/06/2016		Yes	No
Results article	results	02/03/2017		Yes	No
Results article	results	27/02/2020	15/01/2020	Yes	No
Results article		10/03/2021	28/09/2021	Yes	No
Plain English results			25/10/2022	No	Yes
Plain English results			25/10/2022	No	Yes
HRA research summary			28/06/2023	No	No

Editorial Notes

25/10/2022: Cancer Research UK plain English results links added.
28/09/2021: Publication reference added.
03/04/2020: The following changes were made to the trial record:
1. The EudraCT number was added.
2. Locations: Southern Ireland was initially intended to open as a recruiting centre, but the site was unable to open for AML17.
02/04/2020: The following changes were made to the trial record:
1. The overall end date was changed from 01/07/2014 to 31/12/2020.
2. The target number of participants was changed from 2800 to 2700.
15/01/2020: Publication reference added.
13/12/2016: Publication reference added.
29/02/2016: Publication reference added.
15/02/2016: Publication reference added.

22/02/2011: The following changes were made to the trial record:
1. The overall trial end date was changed from 01/10/2013 to 01/07/2014.
2. The target participant number was changed from 2500 to 2800.

24/06/2008: The following changes were made to the trial record:
1. The overall trial start date was changed from 01/10/2007 to 01/09/2008.
2. The overall trial end date was changed from 01/08/2012 to 01/10/2013.
3. The sources of funding field was updated. Previous sources of funding:
1. Medical Research Council (MRC) (UK) (decision pending)
2. Cephalon UK Ltd (UK) (providing arsenic trioxide and CEP-701)
3. Wyeth (UK) (providing Mylotarg® and temsirolimus)
4. Vion (UK) (providing cloretazine)
5. Bioenvision Ltd (UK) (providing clofarabine)