Optimising Therapy in FLT3-mutated Acute Myeloid Leukaemia

Optimise-FLT3 seeks to build on the results of the AML19 trial which confirmed the feasibility of adding Mylotarg to standard DA+Midostaurin therapy (the so-called ‘Midotarg’ regimen) and also demonstrated the potential superiority of using FLAG-Ida-GO as backbone chemotherapy in these patients. The trial design has been shaped during discussions within the NCRI AML Trials Subgroup and was supported by UK AML clinicians during discussions at the 2022 and 2023 AML Academy meetings. Optimise-FLT3 will recruit 399 adults with newly diagnosed, FLT3 mutation positive AML who are suitable for intensive therapy with curative intent. We aim to open 70-80 research sites in the UK with additional sites in Denmark and New Zealand, with recruitment expected to open in October 2024 for 3.5 years followed by a 2-year follow-up period. Overall, the trial is expected to be open between March 2024 – February 2031. The study has a Phase III, randomised, three-arm, multi-stage design with a 1:1:1 randomisation stratified by age, NPM1 co-mutational status and FLT3 mutation type. Randomisation is between standard of care therapy (DA-Midostaurin) and 2 experimental arms, namely DA-GO-Midostaurin (‘Midotarg’) and FLAG-Ida-GO-Midostaurin. The primary endpoint will be Event Free Survival (EFS); Events being defined by death, failure to achieve CR after 2 chemotherapy cycles, molecular relapse (for NPM1 co-mutated patients), and frank relapse.