Leukaemia Trial Service Unit Special Project Grant

Lead Research Organisation: University of Oxford
Department Name: Clinical Trial Service Unit

Abstract

There have been a few striking advances in the treatment of leukaemia in the last few decades but most of the improvements, including that seen for children diagnosed with leukaemia, have been the result of an incremental series of small steps. Over the past 30 years, CTSU have been at the forefront of this work in the UK and internationally. The Unit has provided reliable evidence on the effectiveness of treatments in the different types of leukaemia by helping to design randomised trials and by running these trials efficiently. Furthermore by collecting and combining data on each patient in hundreds of trials from many different research groups around worldwide (meta-analysis), CTSU have been able to determine how the benefits and harms of these treatment vary between different types of patient. This application is to allow the continuation of this work. In some cases where the outlook for patients remains poor, there are new treatments which need testing. In others there is a need to determine whether the burden of treatment can be reduced. This is the case in childhood leukaemia, where new techniques allow the identification of low risk children who may not require the current full standard therapy. Trials are separately funded, but this funding does not support the long-term follow-up required to investigate whether benefits are lasting and whether there are any late adverse effects. Core funding is also vital to support the planning work that is needed for future trials and to perform additional analyses, such as the determination of new risk group definitions. The meta-analyses require continuing funding in order to maintain the collaborative groups of research groups that have run trials, who share their data and help interpret the results.

Technical Summary

Leukaemia trials: During the last 5 years, 8 key results have been published from 5 randomised trials coordinated by CTSU, including: (i) in childhood acute lymphoblastic leukaemia (ALL) dexamethasone improves disease outcome compared to prednisolone, and thioguanine in maintenance adds toxicity without providing benefit, (ii) in high risk primary thrombocythaemia (PT) hydroxyurea is superior to anagrelide, (iii) in chronic lymphocytic leukaemia (CLL) fludarabine plus cyclophosphamide improves progression free survival (PFS), and (iv) in adult ALL matched related donor allogeneic stem cell transplant (SCT) improves long term survival, and autologous transplant prevents fewer relapses than chemotherapy. During the next 5 years our priorities will include (i) can results from an in vitro assay of drug sensitivity direct second line treatment of CLL, (ii) does hydroxyurea reduce thrombosis and major haemorrhage when added to aspirin in intermediate risk PT, (iii) is imatinib effective in Philadelphia positive adult ALL, (iv) do high risk children with ALL identified by measurement of minimal residual disease (MRD) have better survival with more intensive treatment, and (v) can treatment be reduced for MRD low risk children to reduce the burden of therapy?

Leukaemia meta-analyses: Collaborative groups of researchers who have coordinated randomised trials in the treatment of childhood ALL, CLL, AML, and myeloma have been established. Individual trials often provide influential results, but meta-analyses of individual patient data from all trials worldwide enable more detailed and robust examination of treatment effects. A lack of resources has stalled some of this work but recent short-term funding has allowed the revival of the childhood ALL collaboration so as to complete work on anthracyclines, thiopurines, steroids, vincristine-steroid pulses, intravenous mercaptopurine and central nervous system-directed therapies. A new collaboration in adult ALL will look at SCT, where treatment-related mortality and relapse risk depend on different patient and disease characteristics and large numbers are needed to examine the harm-benefit balance within subgroups. The same question will be addressed in AML. In CLL, trials have shown that fludarabine plus cyclophosphamide improves PFS but results are inconsistent. The CLL Collaborative Group will provide data for investigating this, and to obtain more reliable estimates of subgroup and overall survival effects.

Core funding is essential to maintain the meta-analysis collaborative groups, to maintain the trial databases, to make the best use of both resources in conjunction with laboratory data and the monitoring of long term adverse effects, and for planning future trials.

Publications

10 25 50
 
Description CTSU QQR 
Organisation Medical Research Council (MRC)
Department MRC/Cancer Research UK/BHF Clinical Trial Service Unit & Epidemiological Studies Unit
Country United Kingdom 
Sector Public 
PI Contribution Please see return for CTSU QQR U137686856
Impact Please see return for CTSU QQR U137686856
Start Year 2008