Condition category
Cancer
Date applied
21/06/2007
Date assigned
02/07/2007
Last edited
29/02/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Prof Alan Burnett

ORCID ID

Contact details

School of Medicine
Cardiff University
Heath Park
Cardiff
CF14 4XN
United Kingdom
+44 (0)29 2074 2375
BurnettAK@Cardiff.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

CU 372-07

Study information

Scientific title

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

Acronym

AML17

Study hypothesis

Best chemotherapy +/- molecular intervention and risk-directed chemotherapy.

Ethics approval

MREC for Wales, 08/10/2008, ref: 08/MRE09/29

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Patient information material can be found at: http://AML17.cardiff.ac.uk

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

Phase

Phase III

Drug names

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 measures

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 trial start date

01/09/2008

Overall trial end date

01/07/2014

Reason abandoned

Eligibility

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 type

Patient

Age group

Adult

Gender

Both

Target number of participants

2800

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

Trial participating centre

Cardiff University
Cardiff
CF14 4XN
United Kingdom

Sponsor information

Organisation

Cardiff University (UK)

Sponsor details

c/o Dr Kathy Pittard-Davies
33-36 Newport Road
Cardiff
CF2
United Kingdom
+44 (0)29 2087 9274
DaviesKP2@Cardiff.ac.uk

Sponsor type

University/education

Website

http://www.Cardiff.ac.uk

Funders

Funder type

Research council

Funder name

Cancer Research UK (CRUK) (UK)

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

Genzyme Ltd (UK) - supplying clofarabine

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Novartis Pharmaceuticals UK Limited (UK) - supplying mTOR inhibitor

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

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

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Bioenvision Ltd (UK) - providing clofarabine

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Results - basic reporting

Publication summary

2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25833957
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26384238
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/26789727
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/26921360

Publication citations

Additional files

Editorial Notes

29/02/2016: Publication reference added. 15/02/2016: Publication reference added. On 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. On 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)