Alan Burnett research projects
CRUK/08/025: AML 17: A Trial for Acute Myeloid Leukaemia and High Risk Myelodysplastic Syndrome in Younger Patients.Funding period: 01 August 2008 to 31 July 2014
Funding scheme: Clinical Trials Awards & Advisory Committee - Late Phase Study
Funding committee: Clinical Trials Awards and Advisory Committee
Younger patients with Acute Myeloid Leukaemia and high risk Myelodysplastic syndrome have a high level of complete response to modern chemotherapy but 50% die, mostly due to relapse. The AML study group conducts the largest trials in the world to address a number of issues in these patients and recruits around 60 patients per month with over 80% of patients in the UK entering the national trial in this age group. The AML17 trial will compare 2 induction chemotherapy (DA vs ADE) schedules which will be combined with one of two dose levels of the immunoconjugate Mylotarg which we have just shown in low dose to significantly reduce the risk of relapse and improve disease free survival. Following induction, patients will be assessed for relapse risk. Patients with a FLT3 mutation will receive chemotherapy with or without the FLT3 inhibitor (CEP-701), those with high risk disease based on a new risk index that we have prospectively validated, will be randomised to receive either conventional chemotherapy (FLAG-Ida) or a novel combination of daunorubicin and the novel agent clofarabine, with the intention of going on to allogeneic transplant.
Other standard risk patients will receive chemotherapy with or without the mTOR inhibitor Temsirolimus. All patients who are not high risk will be randomised to receive a total of 3 versus 4 courses of treatment. The impact of minimal residual disease monitoring on survival will be assessed by randomising patients 'to monitor or not to monitor' disease.
In patients with the APL subgroup the Italian AIDA protocol (ATRA with Anthracycline) will be compared with the 'chemo-free' treatment with ATRA and Arsenic Trioxide. This will be a trial in collaboration with the Italian GIMEMA study group and German study Groups.