Leukaemia Trial Service Unit Special Project Grant

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

Abstract

Although there have been substantial overall advances in the understanding and treatment of leukaemia, these large improvements have generally been achieved by a series of relatively small steps, each involving only a moderate survival gain. New treatments do not, however, always improve survival and large randomised trials are needed to compare new treatments with current standard treatment in order to determine whether there is further benefit. Meta-analyses of such trials, where all the worldwide data is brought together, help to establish the size of any benefits, and can be used to explore whether there are patients with particular characteristics (for instance older versus younger), or with particular types of disease, which benefit more than others. In addition, where the meta-analysis is based on updated (often unpublished) follow-up information on each randomized patient, the long term effects of treatment can be investigated reliably. This allows patients and doctors to make informed treatment decisions that weigh up benefits against side effects.

Some types of leukaemia still have a relatively poor outlook, and very intensive treatments are being tested and new drugs sought for them. Some treatments, such as bone marrow transplant from a related donor, have a high risk associated with them, but if they are shown in proper trials to be effective they may offer long term survival to some patients who would otherwise have died. Conversely, the outlook for the most common type of childhood leukaemia has improved so much that the chances of being alive and free of disease long term are now over 75%, and we need to separate children with a high risk of relapse, who may benefit from more intensive treatments, from those with a low risk of relapse, where it may be possible to minimise side effects by reducing treatment. New laboratory techniques are helping to identify relevant risk groups, but national coordination is needed to address these questions in an appropriately large trial.

CTSU has already provided definite information about the effects of certain treatments, and that information is now incorporated into clinical decision making. This application is for funding of currently running trials, for further meta-analyses, for the development of new trials and for getting rapid recruitment as soon as any trials receive MRC approval.

Technical Summary

Leukaemia meta-analyses: Over the last 10 years, we have established close worldwide collaboration between those who have coordinated randomised trials in childhood or adult acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL), chronic myeloid leukaemia (CML) or myeloma. This collaboration, which involves them sharing with us the detailed data from each of their trials for worldwide meta-analysis of the results, has enabled clear answers to be obtained on some important treatment issues, some involving improved survival (eg intensive chemotherapy blocks in ALL, interferon in CML), some involving similar survival with less toxicity (eg cranial irradiation for childhood ALL can be replaced by long term intrathecal therapy, interferon has little effect on survival in myeloma, combination chemotherapy compared with melphalan plus prednisone in myeloma improves the response rate but not survival, immediate treatment with chlorambucil based therapy for early stage CLL does not confer survival benefit). Over the next 5 years these collaborative groups will answer further important questions (such as which steroid and which thiopurine is best for childhood ALL, whether fludarabine as first line therapy prolongs survival in CLL, what the role of high dose therapy is in myeloma, what place resistance modifiers have in AML, and whether transplants or chemotherapy give the best long term survival in adult ALL). The use of individual patient data greatly increases the reliability of results, and facilitates investigation of whether there are groups of patients who benefit more, or less, from a particular treatment.

Leukaemia trials: Over the past few years, MRC trials have continued in childhood and adult ALL, AML, CLL, CML and primary thrombocythaemia (PT). These trials have generally been increasing in size and hence reliability. Trials currently open are CLL4, CLL5, UKALLXII (adult ALL) and PT1, plus a pilot study in childhood ALL. Others have recently closed (CML5, CML autograft, ALL97/99). All will require from CTSU further follow-up, analysis and collaborative publication during the next 5 or more years. CTSU will also provide statistical support and advice to the newly established NCRI leukaemia study group for all NCRI leukaemia trials. If the new MRC childhood ALL trial is funded, then CTSU will implement it.

Publications

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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 Academic/University 
PI Contribution Please see return for CTSU QQR U137686856
Impact Please see return for CTSU QQR U137686856
Start Year 2008