EHA 2010

Dr Adele Fielding (University College London, UK)

Trials for acute lymphoblastic leukaemia

What was the UKALL 12 trial?

So UKALL 12 was the twelfth trial for adult patients with acute lymphoblastic leukaemia and Professor Tony Goldstone was the chief investigator. It was the largest ever trial for adults with acute lymphoblastic leukaemia and it was a collaborative effort between the United Kingdom and the Eastern Co-operative Oncology Group of the United States.

The trial was split into two parts, it was for patients with Philadelphia chromosome positive and with Philadelphia chromosome negative disease. And it’s produced a vast quantity of data and most of these data have now been published, mostly in the journal Blood. But one part of the study for patients with Philadelphia chromosome positive ALL was kept open a little longer than the main study to accrue the target population. And in this part the addition of the tyrosine kinase inhibitor Imatinib to standard therapy was evaluated.

What data has come out of the trial?

The data are now mature and they’re being prepared for publication but I was presenting the data in which Imatinib was added to therapy during induction and we showed that there was a much higher rate of complete remission and many more patients were able to reach allogeneic bone marrow transplant. And this is translated into an overall survival benefit. This study is quite important because of the vast number of patients entered, the mature follow-up and the large historical control population treated on the same protocol before the advent of Imatinib so that we can compare the outcome with that group.

What will this mean for changes in therapy for Philadelphia chromosome-positive ALL patients?

So there are already numerous smaller studies showing good outcome when Imatinib is used in this disease, nonetheless because these studies have not been randomised controlled trials many physicians struggle to be allowed to prescribe the drug on the grounds of cost. And I hope that the large magnitude of the difference between the Imatinib treated and the control population in this study will put paid to the debate as to whether this drug should be given or not, and it will help UK patients with Philadelphia positive ALL to receive the drug in a timely manner.

What will a trial assess?

We are about to open another large randomised phase III trial within the UK for adults with ALL. This study will assess a number of important questions. Firstly and foremost we’ll examine whether the addition of monoclonal antibodies to the therapy, to standard therapy for patients with B precursor ALL, can impact outcome for these patients.

So patients will be randomised at diagnosis to receive either standard therapy, which will be an adapted, updated, modern version of the UKALL 12 style therapy and monoclonal antibody anti-CD20 or anti-CD22 or both antibodies will be added together. And these drugs will be provided free of charge.

Is the trial just for adults?

The old trial initially included patients from the age of fifteen upwards but there has been a lot of data emerging in the treatment of ALL that younger individuals have a better outcome when treated on a so-called paediatric style protocol. So during the conduct of UKALL 12 we gradually changed the upper age limit for entry, so by the time the trial ended we were entering people only above the age of twenty.

How is the trial funded?

It’s funded by Cancer Research UK with a large and generous grant and it’s going to be run by the UCL Cancer Trials Centre.

Where can people find out about the forthcoming trial?

People with this disease are particularly interested in finding out more about the trial, they can look on the Cancer Research UK website which is a large and good website; it’s easy to access and there’s basic information about the trial. They can also find information on the University College London Cancer Trial Centre website.