Plain English Summary
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
MRC AML12 (modified)
Study information
Scientific title
Acronym
Study hypothesis
Added as of 07/03/2007:
To compare two methods of administering all-Trans Retinoic Acid (ATRA) to patients with acute promyelocytic leukaemia (APL, FAB AML-M3) - either ATRA for 5 days only before the introduction of trial induction chemotherapy or continuous ATRA during induction chemotherapy until complete remission is achieved (or for a maximum of 60 days) with respect to differences in haemorrhagic complications, induction deaths, remission rate, remission duration and overall survival. To evaluate the role of ATRA in correcting the coagulopathy associated with APL. - To investigate the two methods of using ATRA therapy with respect to the sequence of change of laboratory parameters of coagulation and thrombolysis, and blood product usage. To evaluate cytogenetic and molecular monitoring of disease status with reference to the prediction of morphological leukaemia relapse.
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
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Leukaemia (acute)
Intervention
Four randomised comparisons:
At diagnosis:
1. S-DAT versus H-DAT
2. All-trans-retinoic acid (ATRA) versus not (except for acute promyelocytic leukaemia (APL) patients who will receive ATRA)
After course 3:
3. 4 versus 5 courses of total therapy
4. Bone marrow transplant (BMT) versus chemotherapy as the final course of therapy
Added 08/09/09: A trial with 250 patients would have a power of 50% to detect (at 2p=0.05) a 10% absolute difference in remission rate or long term survival between the two ATRA groups. If no difference were apparent between the two arms the possibility that one arm is greatly superior to the other (ie more than 50% better) would be eliminated. With extended collaboration (UK and internationally) to recruit a total of 500 patients the trial would have a power of about 90% to detect a 10% difference in remission rate and a power of about 50% to detect a 5% difference.
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measures
Added as of 07/03/2007:
Haemorrhagic complications, induction deaths, remission rate, remission duration, overall survival and the role of ATRA in correcting the coagulopathy associated with APL.
Secondary outcome measures
Not provided at time of registration
Overall trial start date
01/11/1998
Overall trial end date
01/11/2003
Reason abandoned
Eligibility
Participant inclusion criteria
1. Have one of the forms of AML
2. Are considered suitable for intensive chemotherapy
3. Are normally under the age of 60 years, but can be older as long as intensive therapy is considered suitable
4. Have given written informed consent
Participant type
Patient
Age group
Adult
Gender
Not Specified
Target number of participants
500
Participant exclusion criteria
Added as of 07/03/2007:
1. Previously received any treatment for APL
2. Other forms of AML (including CML in promyelocytic blast crisis)
3. Another concurrent active malignancy
4. Pregnant or consider the possibility of becoming pregnant during the course of treatment
Recruitment start date
01/11/1998
Recruitment end date
01/11/2003
Locations
Countries of recruitment
United Kingdom
Trial participating centre
UKCCCR Register Co-ordinator
London
NW1 2DA
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
Federal/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
Results - basic reporting
Publication summary
1. 2001 results on relationships between age at diagnosis, clinical features, and outcome of therapy in http://www.ncbi.nlm.nih.gov/pubmed/11535502
2. 2001 results on FLT3 duplication as a prognostic risk factor in chemotherapy in http://www.ncbi.nlm.nih.gov/pubmed/11535508
3. 2005 results in http://www.ncbi.nlm.nih.gov/pubmed/16076872
4. 2006 results in http://www.ncbi.nlm.nih.gov/pubmed/16445830
5. 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/20038732
6. 2010 pooled analysis of prognostic significance of rare recurring chromosomal abnormalities in http://www.ncbi.nlm.nih.gov/pubmed/20385793 (see also ISRCTN17161961)
Publication citations
-
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.
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Results
Rao A, Hills RK, Stiller C, Gibson BE, de Graaf SS, Hann IM, O'Marcaigh A, Wheatley K, Webb DK, Treatment for myeloid leukaemia of Down syndrome: population-based experience in the UK and results from the Medical Research Council AML 10 and AML 12 trials., Br. J. Haematol., 2006, 132, 5, 576-583, doi: 10.1111/j.1365-2141.2005.05906.x.
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Webb DK, Harrison G, Stevens RF, Gibson BG, Hann IM, Wheatley K, , Relationships between age at diagnosis, clinical features, and outcome of therapy in children treated in the Medical Research Council AML 10 and 12 trials for acute myeloid leukemia., Blood, 2001, 98, 6, 1714-1720.
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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.
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Burnett AK, Hills RK, Milligan DW, Goldstone AH, Prentice AG, McMullin MF, Duncombe A, Gibson B, Wheatley K, Attempts to optimize induction and consolidation treatment in acute myeloid leukemia: results of the MRC AML12 trial., J. Clin. Oncol., 2010, 28, 4, 586-595, doi: 10.1200/JCO.2009.22.9088.
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Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, Wheatley K, Harrison CJ, Burnett AK, , Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials., Blood, 2010, 116, 3, 354-365, doi: 10.1182/blood-2009-11-254441.