Condition category
Cancer
Date applied
25/10/2000
Date assigned
25/10/2000
Last edited
26/09/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof AK Burnett

ORCID ID

Contact details

Department of Haematology
University of Wales College of Medicine
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

G8223452

Study information

Scientific title

Acronym

AML 12

Study hypothesis

To improve the outcome of patients with newly diagnosed AML by randomised evaluation of:

1. Standard dose (100 mg/m2 b.d.) versus higher dose (200mg/m2 b.d.) Ara-C within a DAT (daunorubicin, Ara-C, thioguanine) induction regimen (courses 1 and 2)
2. The addition of retinoic acid (ATRA) during and after induction chemotherapy (courses 1 and 2)
3. Four versus five courses of therapy in total (where the final course is either chemotherapy or transplant)
4. Bone marrow transplantation (BMT) (either allogenic or autologous) versus conventional chemotherapy as the final course (good risk patients should not be entered into this randomisation).

The therapeutic relevance of morphology, cytogenetics, molecular genetics and immunophenotype will also be investigated.

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Leukaemia

Intervention

Four randomised comparisons:
1. S-DAT versus H-DAT
2. All-trans retinoic acid (ATRA) versus control
3. 4 versus 5 courses of therapy in total
4. Bone Marrow Transplant (BMT) versus chemotherapy as the final course

Intervention type

Other

Phase

Not Specified

Drug names

Primary outcome measures

Survival; complete remission (CR) rates and reason for failure; duration of remission; toxicity; quality of life; supportive care requirements.

Secondary outcome measures

Not provided at time of registration

Overall trial start date

01/10/1994

Overall trial end date

01/01/2001

Reason abandoned

Eligibility

Participant inclusion criteria

1. Acute myeloid leukaemia (AML) (any type of de novo or secondary AML, including acute promyelocytic leukemia [APL])
2. Suitable for intensive therapy
3. Normally under the age of 60 years (but older patients can be entered if considered suitable)
4. Informed consent given

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Not provided at time of registration

Participant exclusion criteria

1. Previous cytotoxic therapy for leukaemia
2. Concurrent active malignancy
3. Blast transformation of CML
4. Pregnant or lactating
5. Intensive chemotherapy not considered to be an appropriate treatment option
6. Patients with APL are not eligible for the ATRA randomisation

Recruitment start date

01/10/1994

Recruitment end date

01/01/2001

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Department of Haematology
Cardiff
CF14 4XN
United Kingdom

Sponsor information

Organisation

Medical Research Council (MRC) (UK)

Sponsor details

20 Park Crescent
London
W1B 1AL
United Kingdom
+44 20 7636 5422
clinical.trial@headoffice.mrc.ac.uk

Sponsor type

Research council

Website

http://www.mrc.ac.uk

Funders

Funder type

Research council

Funder name

Medical Research Council (MRC) (UK)

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

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

Results - basic reporting

Publication summary

2001 results in http://www.ncbi.nlm.nih.gov/pubmed/11535508
2005 results in http://www.ncbi.nlm.nih.gov/pubmed/16076872
2010 results in http://www.ncbi.nlm.nih.gov/pubmed/19965647
2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23439754
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24855211

Publication citations

  1. Results

    Kottaridis PD, Gale RE, Frew ME, Harrison G, Langabeer SE, Belton AA, Walker H, Wheatley K, Bowen DT, Burnett AK, Goldstone AH, Linch DC, The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials., Blood, 2001, 98, 6, 1752-1759.

  2. Results

    Gale RE, Hills R, Kottaridis PD, Srirangan S, Wheatley K, Burnett AK, Linch DC, No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML10 and 12 trials., Blood, 2005, 106, 10, 3658-3665, doi: 10.1182/blood-2005-03-1323.

  3. 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.

  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

    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.

Additional files

Editorial Notes