ASTIC Trial - Patient information

Unfortunately, some patients fail to respond to best clinical treatment in Crohn’s disease and some only experience temporary benefit, which is why the search for more effective treatments is continuing. Recently, an experimental treatment has been developed for severe Crohn’s disease, called ‘high dose immunoablation followed by autologous hematopoietic stem cell transplantation’. Hematopoietic blood stem cells are young, undifferentiated blood cells that can develop into differentiated ones, including lymphocytes, and over-reactive lymphocytes are thought to contribute to the development of Crohn’s disease. These stem cells have nothing to do with embryonal stem cells or cloning of organs or individuals. This study involves removing your over-active lymphocytes (immunoablation) and replacing them using blood stem cells that had been taken (harvested) from your body earlier in the study. Conventional medication only temporarily suppresses the over-reactive lymphocytes.

At present, about 30 patients suffering from Crohn’s disease have been treated with stem cell transplantation worldwide. The results from those studies suggest that the therapy may be effective, but it cannot be concluded yet whether this treatment is better than any best clinical practice. An international collaborative group of medical specialists has agreed that this issue can only be solved by conducting a scientifically sound clinical study in which institutions from all over the world participate. This study is a European collaboration and we aim to treat a total of 48 patients in the different countries that are taking part.

In the first stage of this study, stem cells will be removed (harvested) from all patients in a process called mobilisation. Drug treatment is used to mobilise the stem cells from your bone marrow, so that some of them can be harvested from the blood and stored for later use. It is useful to know that the drug used for mobilization your stem cells is also effective against Crohn’s disease, thus this preparatory phase results in a treatment by itself.

Patients will then be randomly assigned to undergo immunoablation and autologous stem cell transplantation either 4 weeks after mobilisation (early stem cell transplantation) or 59 weeks after mobilisation (delayed stem cell transplantation). Immunoablation means the elimination of the stem cells in your body, and is achieved by combining high doses of cyclophosphamide and antithymocyte globulin, both administered by infusion. Then the stem cells that were harvested earlier are transplanted (re-infused) into your blood, like a regular blood transfusion thereafter homing into the bone marrow. The re-infused stem cells give rise to a new generation of immune cells, replacing cells of the original ‘sick’ immune system.

By comparing the progress of patients who undergo early stem cell transplantation with those who receive late blood stem cell transplantation, the study will allow the value of immunoablation and stem cell transplantation to be assessed, whilst offering this new procedure to all patients that enter the study. It is possible that the process of mobilisation may give some benefit. The study will allow some assessment of this effect and control for it when assessing transplantation.

As well as the experimental treatment, all patients will receive any existing treatment they need, according to best current clinical practice. This will normally include the use of corticosteroids, immunosuppressive drugs and infliximab.

Because this is an experimental technique, we have to tightly control which patients take part. This will avoid patients who are at high risk of experiencing serious side-effects from entering the trial, and will ensure that we get useful results. If a doctor is considering entering you into the study he or she will make sure that you meet the following criteria:

You must:

• be aged between 18 and 50 (Patients aged up to 65 may be allowed if the group organising the trial agree that they can safely take part)
• have a confirmed diagnosis of Crohn's disease that is active at the time when you enter the study
• have not been successfully treated for Crohn's disease in the past, despite trying three immumosuppressive drugs and corticosteroids, or being intolerant to immunosuppressive drugs
• have an impaired quality of life
• have symptoms that are not suitable to be treated with surgery
• be willing to sign the study consent form

You must not: 

• be pregnant, or likely to get pregnant during the time that you are in the study
• have any other severe diseases as well as your Crohn's disease
• have diarrhoea due to a short small or large bowel
• have a significant risk of infection
• have significant malnutrition
• have had problems following previous treatment regimes
• be taking part in any other clinical trial at the same time or in the previous four weeks

Your doctor will carry out a number of detailed tests to make sure that you meet these criteria and are suitable to take part.

See the Centres and Members page for a list of hospitals and investigators participating in the trial.