Aim of the trial:
To determine the effectiveness of new pre-transplant treatments and conditioning therapies for patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS).
Why is the trial important?
A stem cell transplant can be a curative treatment for patients with blood cancer, but unfortunately, they are not always successful. A variety of different pre-transplant treatments and conditioning therapies are now available, but it is difficult to know which combinations will work best in each situation. The patient’s age, general health and the type of blood cancer they have can all influence how effective a treatment might be.
The design of this trial allows multiple new treatments to be analysed at the same time and identify which will work best for patients with different medical needs. Although trials like this are more complex, it is more efficient and cost-effective than running separate trials.
Overall, this trial will determine which treatments can improve the survival and quality of life of patients with AML and MDS, which could lead to them becoming standard treatment options for patients in the future.
Who can take part?
Adults, who are 18 years of age or older, with either AML or high risk MDS who are due to have an allogeneic stem cell transplant.
What will happen to me?
The COSI trial consists of two stages which both test new combinations of existing treatments. At each stage patients will be randomly placed into different groups, with each group receiving a different treatment. Some patients will take part in both stages of the trial, while others will only take part in stage one or stage two.
Stage one – Consolidation treatment
These treatments are given before your transplant to control the progression of either AML or MDS. They stabilise your condition and help bring you into remission so that your stem cell transplant can go ahead. If you are taking part in this stage of the trial, you will receive one of the following:
- A new combination of two chemotherapy drugs called ‘daunorubicin’ (also known as ‘daunomycin’) and ‘cytarabine’.
- The current standard treatment of cytarabine alone.
Stage two – Conditioning therapy
Conditioning therapy is a treatment given just before a transplant to prepare your body for the process. It removes abnormal cells from your blood and creates space in your bone marrow for the donated stem cells to develop and multiply. There are two different types of conditioning therapy: full intensity (or myeloablative) and reduced intensity conditioning (RIC). In general RIC causes fewer side effects and so it is given to older patients, or patients who are too unwell to cope with full intensity therapies.
For this trial, if you are under 55 you will be given one of two types of full intensity conditioning therapy before your transplant.
- A new combination of three chemotherapy drugs – thiotepa, busulfan and fludarabine
- The current standard treatment of fludarabine and busulfan.
If you are over 55, you will be given one of two types of RIC therapies before your transplant. These drug combinations are the same as the full intensity therapies but use lower doses.
How will we know if the trial is successful?
The trial’s first stage will see if the new consolidation drug combination improves patient survival compared to the standard treatment. It will also look at how effective both treatments are at controlling the progression of AML and MDS. This is done by analysing the blood to see if levels of abnormal cells, also known as minimal residual disease (MRD), increase over time. It will also document any side effects caused by either treatment.
When comparing the different types of conditioning treatments in stage two, the study will look at the overall survival of each treatment group. It will record how many patients relapse and how many develop post-transplant complications such as graft vs host disease (GvHD). Regular questionnaires will also determine how these treatments impact the patient’s quality of life.
Stage: Phase 2 and 3
Study lead: Professor Charles Craddock
Recruiting: 869 patients by January 2024
Time: Six to seven years from Jan 2020
Information published: 03/09/20
Next review due: 03/09/23