A trial looking at treatment for older people with acute myeloid leukaemia and high risk myelodysplastic syndrome (AML18)
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 treatment for acute myeloid leukaemia (AML) and high risk myelodysplastic syndrome (MDS). It is designed mainly for people over 60 years of age who are fit enough to have intensive chemotherapy. But some younger people may be able to take part.
The trial is supported by Cancer Research UK.
More about this trial
The trial is trying to answer a number of questions about the treatment of acute myeloid leukaemia (AML) and high risk myelodysplastic syndrome (MDS). High risk MDS means that there is more chance that it will turn into AML over time. MDS is classed as high risk if more than 10% of your 
is made up of immature cells called blasts.
Doctors usually treat AML with chemotherapy to get rid of the leukaemia cells (getting it into . This first part of treatment is called induction therapy and can be a combination of 2 chemotherapy drugs called daunorubicin and Ara-c (DA).
But a trial called AML 16 showed that adding a drug called gemtuzumab ozogamicin reduced the risk of AML coming back. Gemtuzumab ozogamicin (also known as Mylotarg) is a monoclonal antibody that is attached to a chemotherapy drug called calicheamicin. In the AML 16 trial, people had 1 dose of Mylotarg. In this trial, researchers want to see if having a dose of DA with 2 doses of Mylotarg is better than having a new drug treatment called CPX-351.
CPX-351 is similar to daunorubicin and ARA-C. Doctors think it can accumulate within the bone marrow.
Doctors can look closely at the in leukaemia cells. This is called . They classify AML cytogenetics as being good, intermediate or poor risk. The AML 16 trial showed that Mylotarg helped most people, apart from those who had poor risk cytogenetics. So in this trial, people with known poor risk cytogenetics won’t have Mylotarg. They will have the chemotherapy drugs vosaroxin and decitabine.
Please note – doctors are no longer looking for people to take part in the vosaroxin and decitabine group.
The trial will also look at adding a drug called quizartinib to chemotherapy to see if this helps to control leukaemia or MDS for longer. Quizartinib is a type of biological therapy that can stop signals cancer cells use to divide and grow.
Another thing being looked at in this trial is the best treatment for people who have no leukaemia cells showing in their blood or bone marrow after the 1st cycle of chemotherapy (a complete remission). Even with a complete remission, there may still be some leukaemia cells left. This is called minimal residual disease or MRD. Doctors can use different tests to look for MRD. If they show there is residual disease, you may need more treatment.
The trial aims to find out:
- if induction chemotherapy with DA and 2 doses of Mylotarg is better than CPX-351 for people with good or intermediate risk cytogenetics
- if either a short course or a long course of a drug called quizartinib improves treatment
- if knowing whether or not there is minimal residual disease (MRD) after 1 cycle of chemotherapy is helpful, and if the outcome of treatment can be improved by making it more intensive for people who do still have MRD after the 1st cycle
- whether having another treatment cycle of DA works better for people who have had MRD after 2 treatment cycles of DA chemotherapy
- whether vosaroxin and decitabine work for people with known adverse risks cytogenetics at diagnosis
The researchers also want to assess the value of having a stem cell transplant using cells from a donor for people taking part in this trial.
Who can enter
You may be able to join this trial if all of the following apply. You:
- have acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) that is considered to be high risk because more than 10% of your bone marrow is made up of immature cells called blasts
- are over the age of 60.
- have satisfactory results of blood tests showing how well your liver and kidneys are working
- 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 during the trial and for a number of months afterwards if you are sexually active and there is any chance you or your partner could become pregnant
You cannot join this trial if any of these apply. You:
- have a type of AML called acute promyelocytic leukaemia (APL)
- have already had chemotherapy or radiotherapy for AML apart from a low dose of hydroxycarbamide (or a similar drug)
- had chronic myeloid leukaemia (CML) that is turning into acute myeloid leukaemia (this stage of CML is called the blast phase)
- have any other type of cancer apart from basal cell skin cancer
- are pregnant or breastfeeding
- are known to have HIV
- have had heart problems such as
angina that isn’t stable and a heart attack in the last 3 months
You cannot join the part of the trial looking at adding the drug quizartinib if you have certain heart problems or take medication that could affect your heart (the trial team can advise you about this). Or if you are going to join the group of people having vosaroxin and decitabine.
Trial design
This is a phase 2/3 trial. The researchers need 2,000 people to take part. At different points in the trial, the people taking part are put into groups by computer. Neither they, nor their doctors can decide which group they are in. This is called randomisation.
You have chemotherapy in cycles of treatment. Each cycle is made up of the time when you have the drugs and a period of rest for your body to recover. Your medical team will explain more about how and when you have the chemotherapy drugs at each point in the trial.
For people with low risk cytogenetics
In the first part of the trial, researchers are looking at DA chemotherapy, Mylotarg and CPX-351.
People who have good or intermediate risk cytogenetics will be randomised to have 1 of the following as their first course of treatment:
- a cycle of DA chemotherapy and 2 doses of Mylotarg – this is arm A
- CPX-351 – this is arm B
Neither you nor your doctor can choose which treatment you will have. And you are 2 times more likely to have CPX-351 than DA chemotherapy with Mylotarg.
Arm A
You have DA chemotherapy as a drip into your bloodstream (intravenously) over 10 days. You stay in hospital to have this treatment.
You also have Mylotarg intravenously. You have it on the 1st and 4th day of your chemotherapy cycle.
Arm B
You also have CPX-351 as a drip into your bloodstream. You have it on days 1, 3 and 5 of your treatment cycle.
Treatment after course 1
After treatment with arm A or B, the researchers will look at samples of your blood and to see if there are any leukaemia cells left. If there aren’t any, you are in complete remission. But your doctor will do tests to look for signs of any leukaemia cells left behind (minimal residual disease or MRD).
The treatment you have next depends on whether you are in complete remission or not.
If you are in complete remission
You have 1 more treatment cycle of DA if you had DA and Mylotarg treatment during course 1. After this you have one of the following:
- a 3rd cycle of DA chemotherapy
- treatment with intermediate dose cytarabine (IDAC) for 5 days
You have 2 more cycles of CPX-351 if you had this treatment during treatment course 1.
After the 1st cycle of chemotherapy, everybody who had DA may also be randomised to have either quizartinib or no drug.
If you are in the quizartinib group, you take it as tablets once a day for 2 weeks after each cycle of chemotherapy. When you have finished chemotherapy, you take quizartinib tablets for another 28 days. Some people will continue to take it for up to a year. Your doctor will explain if this applies to you.
If there are still signs of leukaemia cells
If you had DA and Mylotarg before (arm A), you might have 2 more cycles of treatment. You might have one of the following:
- 2 more treatment cycles of DA
- A cycle of chemotherapy called FLAG-Ida, followed by 1 cycle of chemotherapy called mini FLAG-Ida (people over 70 will have mini FLAG-Ida for both cycles)
FLAG-Ida is made up of the drugs:
Mini FLAG-Ida is made up of the same drugs, but some are at lower doses.
People who had treatment with CPX-351 before (arm B) will have 2 more cycles of CPX-351. You have different doses of CPX-351 depending on which treatment arm you are randomised.
After the 1st cycle of chemotherapy, everybody who had DA may also be randomised to have either quizartinib or no drug. Your doctor can tell you more about this.
For people with known high risk cytogenetics – this group is now closed
You have at least 2 and up to 5 cycles of treatment with the chemotherapy drugs:
- vosaroxin
- decitabine
The number of cycles of treatment you have depends on your needs.
You have both drugs as a drip into a vein. It takes up to 10 minutes to have vosaroxin and about an hour to have decitabine. You stay in hospital for about 5 days during each cycle treatment.
Both groups
As well as the treatments described above, you may be able to have a stem cell transplant if a suitable donor is available.
The trial team will ask you to fill out questionnaires before you start treatment, after 1 month, 3 months, 6 months and a year. The questionnaires will ask about side effects and how you’ve been feeling. This is called a quality of life study.
Hospital visits
You have up to 3 cycles of chemotherapy lasting 4 to 6 weeks each. You are likely to be in hospital for between 3 and 5 weeks in each cycle of treatment. Some people will also continue to take quizartinib for up to a year.
Your doctor or specialist nurse will explain how and when you have the different drugs in this trial and how often you will need to go to hospital for tests and treatment.
Side effects
The most common side effects of the chemotherapy drugs include:
- feeling or being sick
- constipation
- diarrhoea
- sore mouth
- hair loss
- a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
The most common side effects of Mylotarg include:
- shivering when you have the drug
- changes to your liver
Quizartinib is a new drug, there may be side effects we don’t know about yet. The possible side effects include:
- diarrhoea
- high temperature
- lung infections
- tiredness (fatigue)
- feeling sick
- a drop in the number of red blood cells (anaemia)
- loss of appetite
A possible side effect of quizartinib is greying of your hair.
If you have quizartinib, you have regular during treatment. If any of these are abnormal, your doctor may ask you to stop having the trial drug for a while, until the trace goes back to normal.
Your doctor or specialist nurse will talk to you about all the possible side effects of the different drugs before you start treatment.
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 Nigel Russell
Supported by
Cancer Research UK
Cardiff University
Experimental Cancer Medicine Centre (ECMC)
National Cancer Research Institute (NCRI) AML Working Party
Other information
This is Cancer Research UK number CRUK/12/043.
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
