New drugs and biological agents are changing the way that leukaemia and other cancers are being treated but each new drug has to go through a rigorous process of testing before it is accepted as a standard of care treatment. For this reason, clinical trials play a vital role in the introduction of new and improved treatments in the UK. For most cancer patients, asking about the availability of clinical trials is a very good thing to do.
We have information about three current UK clinical trials provided by one of the Professors leading the development of ALL trials.
This is the main national trial for new patients with ALL aged 25 to 65. It is a standard of care to be offered this trial and if patients decide to enter this trial they may get access to drugs that may improve the outcome of their disease. The trial is open in nearly 70 centres in the UK.
Patients with B cell disease will be randomised to receive the B cell antibody rituximab, or not (50/50 chance)
Relapse is a common problem for adults with ALL, occurring in up to one half of patients who receive intensive treatment. Cure is still possible for patients with relapse but first a second complete remission must be attained followed by an allogeneic bone marrow transplant.
Current therapy has quite a lot of side effects (toxicity) so we are trying to improve the outcome of relapsed ALL by testing 2 new agents that are active in patients with B cell disease: Blinatumamab and Inotuzamab. Initial studies in small numbers of patients show both drugs are active but before they can be used in UK patients they will need to be shown to be better than the existing therapy. Most centres in the UK currently use FLAG plus or minus Idarubicin. Some centres will use a regimen containing Clofarabine.
Some patients say ‘why can’t we all have the new drug?’ This is understandable but the answer is that the new drugs simply haven’t been shown to be better. Patients entering into a trial cannot assume they will get a benefit; they might get the new drug and it might be better. We believe both drugs will benefit ALL patients in the future but certainly do not know which one is better. Leukaemia trials in the UK have been taking place for over 40 years and have resulted in big improvements
In this trial patients with relapsed disease (and some patients who do not achieve a remission at all) are randomised to either Inotuzamab or the standard chemotherapy used at the centre they are being treated. They have a 50% chance of getting the experimental treatment and a 50% chance of getting the standard treatment.
Inotuzamab is an antibody to CD22 (a protein antigen on the cell surface of most patients with B cell ALL) that is linked to a toxin called Calicheamicin. So this is a way of delivering a toxic drug specifically to leukaemia cells. It does however have side effects including chills and fever with the infusion, low blood counts and effects on the liver.
The response to treatment is assessed 4 weeks after the start of therapy and again after the next course by a bone marrow biopsy.
This trial is a randomised trial of blinatumamab versus standard of care chemotherapy. Two thirds of randomised patients get the trial drug and one third standard chemotherapy. This drug is unusual in being given as a continuous infusion for 28 days. This sounds daunting but there is a good infrastructure to support this way of giving the drug. Patients need to be in hospital for the first few days as fevers, chills are common. Effects on the brain can occur but are treatable and reversible in the vast majority of cases. Your doctor will explain these side effects to you in detail. Assessment of response occurs after each course of therapy.
Most patients who respond to treatment will be offered a bone marrow transplant. The goal is to get relapsed patients into remission as smoothly as possible and to proceed to transplant very quickly while the disease is under control.
If you want to find out more about these or other clinical trials, please talk, in the first instance to your consultant. We feel that every patient has a right to access to information about clinical trials and access to the trials. Referral to a centre which has the trial open is something many patients will wish to discuss with their consultant.
Professor David Marks
Bristol BMT Unit