A trial looking at dasatinib for children and young people whose leukaemia has not responded or has come back after treatment (CA 180018)

Please note this trial is no longer recruiting patients.

This trial is looking at dasatinib, for children, teenagers and young people with leukaemia which has not responded or has come back (relapsed) after treatment. The trial is for children and young people up to and including the age of 20. We use the term ‘you’ in this summary, but of course if you are a parent, we are referring to your child.

Dasatinib is a type of biological therapy. It aims to block the signal which tells leukaemia cells to grow. In some people, the leukaemia cells have an abnormal chromosome called the Philadelphia chromosome. This is called Philadelphia positive leukaemia.

Research has shown that dasatinib can help adults with Philadelphia positive leukaemia that has not responded to other treatments. The effects of dasatinib have not been looked at in children and dasatininb has not been looked at in people with leukaemia which does not have the Philadelphia chromosome.

The aim of this trial is to find out

The best dose of dasatinib to treat children and teenagers
What side effects happen in children and teenagers
How well this treatment works in different types of leukaemias

Recruitment

Start 09/05/2006

End 09/10/2009

Phase

Phase 1/2

Who can enter

You can enter this trial if you have been diagnosed with either

Philadelphia positive chronic myeloid leukaemia (CML), and treatment with imatinib (Glivec) is no longer working (your doctor will tell you more about this) OR
Philadelphia positive acute lymphocytic leukaemia (ALL) or Phildelphia positive acute myeloid leukaemia (AML) which has come back after treatment with imatinib in the past (Please note - the imatinib does not need have been the most recent treatment) OR
Any type of Philadelphia negative leukaemia which has come back, and there are no other treatment options

As well as this, you can enter this trial if you

Are aged between 1 and 20 years (inclusive)
Have recovered from the side effects of previous treatment
Are well enough to take part (performance status 0,1 or 2)
Have satisfactory blood test results and tests to check your heart function is normal
Are prepared to use reliable contraception while taking part in the trial, if there is any chance that you or your partner could become pregnant

You cannot enter this trial if you

Have been recommended to have a bone marrow transplant within the next 6 weeks, to try and cure your leukaemia
Have leukaemia which has spread from the bone marrow to other organs in the body (this is called extramedullary disease) and is causing symptoms
Have had any experimental or standard treatment for your leukaemia within the last 2 weeks (this does not include imatinib, hydroxyurea, steroids, 6-mercaptopurine or 6-thioguanine)
Have taken dasatinib in the past
Are taking medication that might affect your heart rate or blood clotting (your doctor will be able to tell you more about this)
Have any other serious medical condition which the doctors think will affect the treatment
Are pregnant or breastfeeding

Trial design

This trial will recruit about 50 children and young people. Everyone taking part will take dasatinib by mouth, once a day. Each 3 week period is one cycle of treatment.

The first children taking part will have the lowest dose of dasatinib. If they do not have any serious side effects, the next children will have a higher dose and so on until the doctors find the best dose to give. This is called a 'dose escalation' study. It aims to find the dose of dasatinib that works the best, while causing as few side effects as possible. The dose will also depend on what type of leukaemia you have and how much you weigh.

You may take dasatinib for up to 4 years depending on how well the treatment is working, and whether you have any side effects.

Hospital visits

You will go to the hospital for some tests before you can take part in the trial. These include

Physical examination
Heart trace (ECG)
A test to see how well your heart is beating - either a heart ultrasound (echocardiogram) or a MUGA scan
Chest X-ray
Bone marrow test
Blood tests

You may have a lumbar puncture before you take part in the trial.

You will go to the hospital every week for the first 6 weeks and then at least every 3 weeks after that. During the trial you will need further tests, which include

Blood tests every week for the first 6 weeks and then every 3 weeks after that
Physical examination every 12 weeks
Chest X-ray every 12 weeks
ECG after 10 days, and after any dose increases
Heart scan after 12 weeks, and then every 6 months
Bone marrow tests every 4 to 12 weeks, depending on what type of leukaemia you have

On the first day of treatment, the doctors will take a series of blood tests to measure the amount of dasatinib in your bloodstream. They will only repeat these blood tests if later on, they increase the dose of dasatinib.

Throughout the trial the doctors will take extra blood samples to monitor the leukaemia level in your blood. Special 'molecular and cytogenetic' tests will be used to monitor the Philadelphia positive leukaemias . If you are female and are able to become pregnant, the doctors will do a pregnancy test before treatment, and then every 12 weeks after that.

At the end of the study you will see the research doctors and have more tests. You may need to carry on seeing the research team if you are still having any side effects from the treatment. After that you will continue to see your own doctor as usual. The doctor will talk to you about your treatment options at the end of the trial.

Side effects

The most common side effects of dasatinib are

A drop in blood cell counts causing an increased risk of infection, bleeding or bruising problems, tiredness and shortness of breath
Diarrhoea
Feeling sick
Headache
Water retention (for example swollen ankles)
Shortness of breath
Skin rash
Muscle or joint pain