AML18

AML18 is an international trial looking at treatment for acute myeloid leukaemia (AML) and high risk myelodysplastic syndrome (MDS) across approximately 90 centres in the UK and Denmark. It is designed mainly for people over 60 years of age who are fit enough to have intensive chemotherapy.

AML 18 is the replacement for the AML16 intensive trial. There are about 2,000 cases of acute myeloid leukaemia (AML) diagnosed in the UK each year. We are looking to build upon our previous results, and improve outcomes for patients within this trial.

In this trial, participants with AML, or high risk myelodysplastic syndrome (MDS), excluding people with the acute promyelocytic leukaemia subtype, will be randomised to receive a number of different therapies. We have previously shown that in patients who do not have poor risk disease, as defined by cytogenetics, a drug called gemtuzumab ozogamicin (GO, Mylotarg) is beneficial. This first part of AML18 assessed the best way to give Mylotarg, either in one dose, or in two doses combined with standard chemotherapy (daunorubicin and Ara-C also known as DA chemotherapy). The second part of AML18 will compare standard chemotherapy (DA) combined with 2 doses of Mylotarg against CPX-351 as course 1 of treatment.

Our previous work in AML16 has shown that the outcome of patients depends on whether they have measurable disease using sophisticated molecular techniques after their first course of treatment. For participants who have residual disease of any sort and who received DA (+/- mylotarg) in course 1, we are testing whether intensifying treatment using a drug called FLAG-Ida can improve outcomes.

For people with no residual disease, who received DA (+/- mylotarg) in course 1 we have shown that 3 courses of chemotherapy is better than 2 courses. We are looking to identify the best treatment for the third course, comparing daunorubicin plus Ara-C versus Ara-C alone at a higher dose.

Finally, we are looking at whether adding a drug called quizartinib (AC220) to chemotherapy for this group of patients, and also for 1 year following treatment can improve outcomes.

For patients who received CPX-351 in course 1 and have residual disease of any sort after their first course of treatment, we are comparing the standard dose of CPX-351 as course 2 treatment with a repeat of the higher dose given in course 1 followed by a third course of CPX-351.

Patients with no residual disease who received CPX-351 in course 1 will be given a further 2 courses of CPX-351. We will also collect further details on treatment using stem cell transplantation to identify who benefits from this treatment.

The trial will recruit for 6 years from about 90 centres in the UK and Denmark. The total number of patients to be included is up to 2,000.

Recruitment end date is 31 December 2022; patient follow up will end mid-2025.

Results

The trial team plans to submit the first high-impact outputs from AML18 in early 2023; publications will continue until the trial formally closes in 2025/26.