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
AML 12 - Acute myeloid leukaemia Adults (modified)
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 measure
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 (if study stopped)
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 (0)20 7636 5422
clinical.trial@headoffice.mrc.ac.uk
Sponsor type
Research council
Website
Funders
Funder type
Research council
Funder name
Medical Research Council (MRC) (UK)
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
National government
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
Basic results (scientific)
Publication list
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
2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/29025912 (added 25/07/2019)
Publication citations
-
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.
-
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.
-
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.
-
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.
-
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.