OPTIMISE-FLT3

The OPTIMISE-FLT3 study focuses on a subgroup of AML with mutations in the FLT3 gene, found in about one-third of AML patients.

Acute myeloid leukaemia (AML) is an aggressive blood cancer and is the commonest form of acute leukaemia in adults, affecting more than 3000 people per year in the UK, the majority of who will die from the disease. Younger and fitter patients can have treatment aiming to cure the disease with cycles of intensive chemotherapy followed for some patients by stem cell transplantation. Survival rates have gradually increased following improvements to chemotherapy, transplantation, better general care measures and the addition of various new targeted drugs for patients in specific AML sub-groups.

This study focuses on a subgroup of AML with mutations in the FLT3 gene, found in about one-third of AML patients. These patients have worse overall outcomes due to increased rates of early disease relapse. Clinical trials in recent years have identified several promising strategies to improve outcomes for patients with FLT3 AML including 1) using an intensified 3-drug chemotherapy protocol called FLAG-Ida 2) adding a drug called midostaurin to inactivate FLT3 and 3) adding a chemotherapy linked-antibody called Gemtuzumab Ozogamicin (also called GO or Mylotarg) but these approaches have not yet been combined in a single trial.

The Optimise-FLT3 trial wants to establish the best way to treat FLT3-AML. Currently the standard treatment is standard intensity chemotherapy (called DA) combined with midostaurin (the FLT3 inactivating drug). We will compare this standard treatment with two new combinations.  One is standard intensity chemotherapy combined both midostaurin and GO; this combination has already undergone pilot testing in the AML19 study and was safe and appeared very effective.  The second new combination is intensified chemotherapy (FLAG-Ida) combined with midostaurin and GO.  Pilot testing of the safety of this combination is built into this study.

Over 4 years, 390 newly diagnosed patients at hospitals around the UK and in partner countries will be randomly allocated to receive one of the three treatment schedules. They will receive up to 4 cycles of intensive chemotherapy treatment, including stem cell transplant in selected cases. The response of the leukaemia to treatment will be measured by standard tests of the blood and bone marrow to see whether patient outcomes are improved in terms of increased survival, reduction in rates of relapse and reduction in the need for stem cell transplant. We will monitor for any increased side effects associated with the intensified treatment schedules.

Results of the trial will be provided to participating patients and their families, presented at international conferences and published in scientific journals. If the trial finds that one of the treatment arms is clearly superior to the others, these results will be used to engage with health bodies to make the treatment with the best results available for future patients across the NHS.