ALLTogether-1 is an international clinical trial looking at improving treatment for acute lymphoblastic leukaemia (ALL). Dr John Moppett, who oversees the trial in the UK, explains more.
The treatment of ALL is a massive success story. In 60 years, we’ve moved from facing a uniformly fatal condition to one where we can cure more than 90% of children and young adults. Progress has been made through the repeated study of potentially better alternative treatments through clinical trials that are run across the world. Two factors are key to this: ial in the UK, explains more.
Best use of conventional chemotherapy drugs:
- Learning what dose and what schedule works best for each drug and in what combinations.
Risk stratification:
- Treatment of leukaemia is potentially toxic and for many years now we’ve used multiple factors to work out how likely an individual patient’s disease is going to respond to treatment (for example: age, white cell count, genetic mistakes found in the leukaemia cells, response to early treatment). This has been critical in helping us to reduce the toxicity of treatment for many patients, whilst still targeting the most intensive and usually toxic therapies at those with the most difficult-to-treat disease.
Collaborating with international colleagues.
Until recently, the UK has run its own series of ALL What do we want to know? clinical trials, that have been very successful in answering questions and improving outcomes. But several years ago, we decided that collaborating with European colleagues was the best way forward, mainly because we need really large numbers of patients to answer our questions.
Over several years, meetings were held with other international groups to develop a joint protocol called the ALLTogether-1 study, which is a collaboration between 14 countries and will recruit nearly 8,000 patients over its six-year duration. It opened in 2020 in a few countries, and in limited UK centres in mid-2021. We’re now in the process of opening the study across remaining sites here in the UK, where it’s currently open to patients up to the age of 30.
What do we want to know?
- Many children with ALL have very curable disease and we believe they can still achieve cure with less treatment – which, in turn, should lead to less toxicity from treatment (particularly severe infections but also other specific drug side-effects). For this group (around half of all patients), we’re asking whether small reductions in how much chemotherapy they receive can be done safely.
- There are still some (individually rare) groups of children with ALL who are more challenging to cure, and we want to improve their chance. We’re studying targeted immunotherapy drugs such as inotuzumab and blinatomomab, and drugs targeting specific genetic mistakes in the leukaemia cells in some of these children, to see if they reduce the risk of relapse. Some patients with very high-risk disease are directed towards separate studies of cellular immunotherapy.
- To ask these questions at the same time, it’s critical that we know which group an individual patient should be placed in. To do this, we’ve developed a world-leading stratification system which we believe is the most accurate in the world.
Helping further studies into ALL.
Through leukaemia samples kindly provided by participants, the study presents an amazing opportunity for scientists to learn more about ALL: why it happens and how to treat it more effectively. We’re also studying better tests to identify those with a greater risk of relapse and better ways to look after patients during treatment. For example, the closely-related CiproPAL study led by Dr Bob Phillips will look at whether antibiotics to prevent infection in the early stages of treatment are beneficial.
From Contact magazine issue 94 - Spring 2022
