Eligibility criteria in acute myeloid leukaemia clinical trials

Dr Mikkael Sekeres - Cleveland Clinic, Cleveland, USA

We’ve done a lot of work around clinical trial eligibility criteria in acute myeloid leukaemia. Our first portion of our work showed that these eligibility criteria are essentially a cut and paste job, they’re random. They have nothing to do with either the expected toxicities of drugs or the realised adverse events on a clinical trial.

The second part of our research actually looked at Southwest Oncology Group patients enrolled to leukaemia studies over a decade. In those studies there were some patients who were found after the fact to have been ineligible for those trials but were treated on them anyway. When we compared the adverse events experienced by those ineligible patients to those who were eligible and the remission rates and survival of those who were ineligible compared to those who were eligible we found that they were essentially the same. In other words, once again, the clinical trial eligibility criteria were too restrictive.

At this year’s ASH we looked at over a thousand patients treated at Cleveland Clinic and we looked at their organ dysfunction or their lab abnormalities that would have gotten them excluded from clinical trials. We found that almost 90% of these patients had either lab abnormalities or comorbidities that could have gotten them excluded from a clinical trial. In other words, one of the reasons we’re not enrolling a lot of patients to clinical trials is because the eligibility criteria themselves prevent us from doing so.

When we looked at which of those comorbidities or lab abnormalities actually could have affected their eligibility and were related to remission rates or overall survival, we really found that it was only chronic hepatic conditions that affected overall survival and should probably be retained as an eligibility criterion for clinical trials in AML. We found that mild abnormalities in kidney function, liver function, heart function actually were unrelated to remission rates or overall survival and therefore those should probably be dropped from clinical trials.