Around 1 in 5 people diagnosed with cancer in the UK take part in a clinical trial.
A trial looking at intensive treatment and ponatinib for chronic myeloid leukaemia (MATCHPOINT)
More about this trial
Doctors often treat CML with biological therapies called imatinib or nilotinib. They are cancer growth blockers called tyrosine kinase inhibitors (TKI’s). They stop signals that cancer cells use to divide and grow. But sometimes these drugs don’t work very well or stop working and your CML gets worse and changes into blast phase. If this happens, your doctor may recommend you have high dose chemotherapy and a stem cell transplant. This is called intensive treatment.
In this trial, doctors want to find out more about a drug called ponatinib alongside intensive treatment for CML that is in blast phase. Ponatinib is also a tyrosine kinase inhibitor. It works in a very similar way to imatinib and nilotinib.
The aims of the trial are to
- Find the best dose of ponatinib for people having intensive treatment for CML that is in blast phase
- See how well ponatinib works for this group of people
- Learn more about the side effects
Who can enter
You may be able to join this trial if all of the following apply.
- You have chronic myeloid leukaemia (CML) that is in the blast phase (your doctor can tell more about this)
- Your CML has a high level of the protein BCR-ABL, or has tested positive for the
Philadelphia chromosome(your doctor can tell more about this)
- You have satisfactory blood test results
- You are willing to use 2 forms of reliable contraception during treatment and for 4 months afterwards if there is any chance you or your partner could become pregnant
- You are at least 16 years old
You cannot join this trial if any of these apply. You
- Have had chemotherapy in the last 4 weeks apart from drugs called hydroxycarbamide, anagrelide, low dose arabinosylcytarabine (LDAC), steroids or interferon
- Have changed treatment to a tyrosine kinase inhibitor (TKI) more than once after your CML got worse and changed to blast phase or you have already had ponatinib
- Have had high dose chemotherapy called FLAG-Ida in the past or you can’t have it for any reason (your doctor can tell you more about this)
- Have had a stem cell transplant using either your own cells or somebody else’s
- Have had major surgery in the last 2 weeks
- Have certain heart problems (the trial team can advise you about this)
- Have had a condition affecting your pancreas called pancreatitis
- Have a high level of fat in your blood (a condition called hypertriglyceridaemia) that isn’t well controlled with medication (your doctor can tell you more about this)
- Are known to be sensitive to a substance in the body called galactose (your doctor can tell you more about this)
- Have any other medical condition that could affect you taking part in this trial
- Are pregnant or breastfeeding
This is a phase 1 trial. The researchers need 30 people to take part. Everyone will have intensive treatment alongside ponatinib.
Ponatinib is a tablet. The first few patients taking part have a set dose of ponatinib. The next few patients have a higher or lower dose depending on the side effects and how well the treatment is working. The dose you have depends on when you join the trial. The trial doctor can tell you more about this.
You start taking ponatinib when you start chemotherapy. Depending on when you join the trial, you take it either once a day or once every other day.
You have ponatinib for as long as it is helping you and the side effects aren’t too bad.
Everyone will also have a combination of chemotherapy drugs called FLAG-IDA. FLAG- IDA includes a drug called G-CSF that stimulates the bone marrow to make new blood cells and the following 3 chemotherapy drugs
You have all the chemotherapy drugs through a drip into a vein. You have G-CSF as an injection under your skin. You have treatment over about 5 to 7 days. You then have a break from FLAG-IDA for 3 weeks. Each 4 week period is called a cycle of treatment. You have up to 2 cycles of treatment.
When you finish chemotherapy, you will have a stem cell transplant if your doctor thinks you are fit enough. If you haven’t recovered from the side effects of chemotherapy or you aren’t well enough, you may not be able to have a transplant. If this happens, you continue having ponatinib alone.
If you do have a transplant, you stop taking ponatinib for a short time. You can start taking it again about 6 weeks after the transplant. The doctors will check your blood test results regularly after your transplant and will let you know when to start taking it again.
The researchers may ask for a sample of your bone marrow and for some extra blood samples and a swab taken from the inside of your mouth. These extra samples may be used in future research to find out more about CML and how to treat it. If you don’t want to give theses samples for research, you don’t have to. You can still take part in the trial.
You see the doctor to have some tests before taking part in the trial. These include
- A physical examination
- Bone marrow test
- Blood and urine tests
- Heart trace (
- Ultrasound of your heart
You have chemotherapy and your stem cell transplant in hospital. You stay in hospital for each treatment cycle. This could be for about 4 to 8 weeks each time. You can go home when your blood test results are satisfactory.
You see the trial doctor every
- week for the first month
- 2 weeks until 6 months
- month for the next 6 months
After that, you see them every 3 months as long as you are taking ponatinib. The doctor will examine you and may repeat some of the tests you had before you started treatment. When you finish the treatment, you go back to see the trial team within a month. The trial team will follow you up for 3 years to see to see how you are getting on. This may be at routine hospital appointment or they may check your medical records to see how you are getting on.
The most common side effects of the drugs used in this trial are
- A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
- Changes to the rate and rhythm of your heart (arrhythmias)
- Liver problems
- Eye problems
- Loss of fertility
- Hair loss
- Headaches, dizziness and migraines
- High levels of
uric acidin your blood
- Numbness and tingling in your hands and feet (peripheral neuropathy)
- A breakdown of tumour cells causing tumour lysis syndrome
- Feeling or being sick
- Skin rash
- Sore mouth
As well as the above, other side effects of ponatinib may include
- Inflammation of the pancreas (pancreatitis)
- Heart problems and stroke
- Chest pain
- An increased risk of blood clots which can cause pain and swelling in your legs or sudden breathlessness and chest pain
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.
Professor Mhairi Copland
ARIAD Pharmaceuticals Inc
Experimental Cancer Medicine Centre (ECMC)
University of Birmingham