A trial comparing usual treatment with new treatments for acute myeloid leukaemia and high risk myelodysplasia (COSI)
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
Cancer type:
Status:
Phase:
This trial is looking at new combinations of chemotherapy before a stem cell transplant to improve treatment.
It is for people who are having a stem cell transplant with somebody else’s cells. This is an 
.
More about this trial
are blood disorders. MDS blood cells have changes in them that make them develop abnormal cells. They might not need treatment for many years, but some go on to develop into acute myeloid leukaemia (AML). High risk MDS means there is more chance it might develop into AML over time. High risk MDS is treated in a similar way to AML.
Chemotherapy is the usual treatment for acute myeloid leukaemia (AML) and high risk myelodysplastic syndrome (MDS). Your treatment is in two phases:
- getting rid of the AML (induction)
- treatment to stop AML coming back (consolidation)
In part of this trial researchers are comparing a new consolidation treatment with . The new combination of chemotherapy includes the drugs daunorubicin and cytarabine. This combination is called vyxeos. The standard treatment is cytarabine on its own.
After chemotherapy some people have a stem cell transplant. You have a combination of chemotherapy drugs before the stem cell transplant. This is called conditioning chemotherapy.
Researchers are also trying to improve conditioning treatment. We know from recent research that the treatment you have just before the stem cell transplant is important. In some blood cancers it reduces the risk of the leukaemia coming back.
In this trial, researchers are looking at different combinations of conditioning treatment. They are comparing new combinations of chemotherapy with . The new combinations include:
- fludarabine, busulphan and thiotepa (TBF)
- lower doses of fludarabine, busulphan and thiotepa (mini TBF)
This trial is in 3 parts. The treatment you have depends on which part of the trial you join.
The main aims of the trial are to:
- see how well the new combinations of chemotherapy work compared with standard combinations
- learn more about the side effects
Who can enter
The following bullet points list the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.
Who can take part
You may be able to join part 2 or part 3 of the trial if one of the following apply. You:
- have no signs of AML in the blood or bone marrow after the first or second chemotherapy treatment (it is in complete remission)
- have AML that developed from MDS (secondary AML)
- have AML and you have had at least 2
courses of high dose chemotherapy before a stem cell transplant. This doesn’t apply if you had a drug called venetoclax and your AML went away completely before your transplant. - have MDS with a high risk of it coming back and less than 10% immature blood cells (blasts) after high dose chemotherapy
As well as the above (for part 2 or part 3), the following must also apply.
You:
- have a matched donor for the stem cell transplant
- are suitable to have a stem cell transplant
- are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
- are willing to use reliable contraception for up to 12 months after treatment finishes if there is any chance you or your partner could become pregnant
- are between 18 and 54 to join part 2
- are 55 years or older to join part 3. You might be able to join part 3 if you are younger than 55 and have other health problems.
Please note that part 1 is now closed to recruitment.
Who can’t take part
You cannot join this trial if any of these apply.
You:
- can’t have a transplant for any reason
- have an active infection that isn’t getting better with treatment
- have a problem with how your kidneys or liver work
- have HIV
- have an active hepatitis B or hepatitis C infection
- have any other cancer unless it was over 5 years ago, was successfully treated and there have been no signs of it since
- are pregnant or breastfeeding
Trial design
This is a phase 2/3 trial. It is a randomised trial. You are put into treatment groups by computer. Neither you nor your doctor can choose which group you are in.
There are 3 parts to this trial. In total, the trial team need 760 people to join the trial. This is made up of:
- 160 people in part 1 (consolidation treatment) - this group is now closed to recruitment
- 160 people in part 2
- 218 people in part 3
The treatment you have depends on which part of the trial you join. And in some cases, your age. Some people may join more than one part of the trial. For example, you might have consolidation treatment in part 1. And then go on to have conditioning treatment in part 2 or part 3. Or you might just join part 2 or part 3. The trial team can tell you more about this.
You have all your chemotherapy as a drip into a vein.
Treatment for AML and MDS (part 1 consolidation treatment) - closed to recruitment
You have 1 of the following:
- cytarabine (standard treatment)
- daunorubicin and cytarabine (a new combination of treatment called vyxeos)
You have up to 2 . Each cycle is over 2 weeks. You have:
- cytarabine over 5 days in each cycle
- vyxeos over 3 days in each cycle
Your doctor will then talk to you about further treatment. You might have a stem cell transplant. Your doctor may ask you to join part 2 or part 3 of this trial. This is looking at treatment you have just before the transplant. This is conditioning treatment.
Treatment for AML and MDS for people who are younger than 55 (part 2)
You have 1 of the following:
- fludarabine and busulphan (standard treatment)
- fludarabine, busulphan and thiotepa (a new combination of treatment called TBF)
You have treatment as a patient in the hospital. You stay there for about 4 to 6 weeks. You have chemotherapy followed by a stem cell transplant.The trial team can tell you exactly when you have the chemotherapy drugs.
Treatment for AML and MDS for people who are 55 or older (part 3)
You have 1 of the following:
- fludarabine and busulphan (standard treatment)
- lower doses of fludarabine, busulphan and thiotepa (mini TBF)
Mini TBF is a new combination of chemotherapy. It is called ‘mini’ because it uses lower doses of chemotherapy than you usually have before a stem cell transplant. Using lower doses of chemotherapy causes fewer side effects than the usual high dose treatment.
You have treatment as a patient in the hospital. You stay there for about 4 to 6 weeks. You have chemotherapy followed by a stem cell transplant. The trial team can tell you exactly when you have the chemotherapy drugs.
Samples for research
You have some extra blood tests. And the researchers ask for some extra samples when you have the bone marrow tests. Researchers plan to use the samples to work out why treatments do or don’t work. They hope this information will help to improve treatment for people with AML and MDS.
Quality of life
The trial team will ask you to fill out a questionnaire before you start treatment and at set times during treatment. The questionnaire will ask about side effects and how you’ve been feeling. This is called a quality of life study.
Hospital visits
You see a doctor and have some tests when you join the trial. These include:
- physical examination
- blood tests
- heart trace (
ECG) - bone marrow test
For part 2 or part 3 you are admitted to hospital to have treatment. The trial team can tell you more about this.
You have regular blood tests to monitor the cancer. In part 1 you have a bone marrow test before treatment and 1 month after treatment.
In part 2 or part 3 you have a bone marrow test before the transplant and at:
- 1 month
- 3 months
For part 1 you have a check up after treatment at:
- 1 month
- 6 months
- 1 year
- 2 years
For part 2 or part 3 you have a check up after treatment:
- at 1 month
- every 3 months for up to 2 years
After 15 months, some of the follow up appointments might be over the phone.
Side effects
The trial team monitor you during treatment and afterwards. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better.
As vyxeos is a new combination of chemotherapy there might be side effects we don’t know about yet. The side effects we know about so far include:
- an increased risk of bleeding which may cause bruising or bleeding
- an increased risk of infection and fever
- slow, fast, or irregular heartbeat or chest pain
- problems with your sight and blurred vision
- pain or swelling of the tissue lining the
digestive system (mucositis) - tummy pain
- constipation or diarrhoea
- loss of appetite
- feeling sick or being sick
- skin rashes, redness or itching
- muscle aches, headache, bone pain, joint pain
- body swelling including swelling of your arms and legs
- tiredness (fatigue)
- headache, dizziness, confusion, difficulty sleeping or anxiety
- kidney problems
- shortness of breath, cough, fluid in the lungs
- high or low blood pressure
- chills, low or high body temperature
- sweating
We have information about the side effects of:
Recruitment start:
Recruitment end:
How to join a clinical trial
Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.
Chief Investigator
Professor Charles Craddock
Supported by
University of Birmingham
The IMPACT Partnership (this includes Leukaemia UK, Anthony Nolan and NHS Blood and Transplant (NHSBT))
Jazz Pharmaceuticals
Adienne
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
