AML15, AML16

In patients given intensive chemotherapy, AML16 for the first time demonstrated the value of measuring response using sophisticated laboratory techniques to identify patients who, although they might be in remission, will relapse early and are therefore candidates for novel treatments or intensification.

The Medical Research Council (MRC) and latterly The National Cancer Research Institute (NCRI) has run trials in acute myeloid leukaemia (AML) continuously since 1960. For over 30 years, clinical leadership has come from Cardiff University, and coordination of the trials was first in Oxford, and then Birmingham, before moving to Cardiff from 2008. Cardiff University has sponsored the trials since the advent of trial sponsorship in 2005.

The running of the AML15 and AML16 trials passed to Cardiff in 2010; and analysis of the results has been done by Cardiff University. These trials remain in long-term follow-up to look at the long-term effect of treatment.

Previous trials in AML had looked at the optimal way of delivering standard drug treatments. AML15 in patients under the age of 60, and AML16 in older patients were the first to look at novel treatments, in particular the drug-linked monoclonal antibody gemtuzumab ozogamicin (GO or Mylotarg). Together, the two trials demonstrated that a single dose of GO could improve survival by up to 5% in patients who did not have poor risk disease as measured by cytogenetics. These two trials make up about 2/3 of the total randomised data for this drug, and have made GO standard of care in the UK.

AML15 demonstrated that for a subgroup of AML called APL, less toxic treatment could be delivered which at the same time improved outcomes. This has led to a change in the standard of care. It also defined the optimal number of courses of treatment to give (4) in younger patients.

AML16, in older patients, embraced the fact that not all older patients are suitable for intensive chemotherapy, and developed a new design, called Pick-A-Winner, to allow rapid identification of potentially beneficial treatments in this group. AML16 unfortunately failed to identify any treatments which improved survival, even though some improved the number of patients entering remission. However, 902 patients were recruited, and 5 novel options investigated – a traditional design would have only allowed two treatments to be evaluated.

In patients given intensive chemotherapy, AML16 for the first time demonstrated the value of measuring response using sophisticated laboratory techniques to identify patients who, although they might be in remission, will relapse early and are therefore candidates for novel treatments or intensification.

The trials process is a continuous one in AML – the results of AML15 and AML16 have informed the designs of the successor trials, AML17, AML18 and AML19.