A study of navitoclax and ruxolitinib for myelofibrosis (TRANSFORM 2)
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
Cancer type:
Status:
Phase:
This study is comparing navitoclax and ruxolitinib with usual treatment for myelofibrosis. It is for people whose myelofibrosis has come back.
The bone marrow is where we make our blood cells. Myelofibrosis is a rare blood disorder. It causes scarring of the bone marrow so it can’t make blood cells properly.
Myelofibrosis can develop without having had any other medical condition. This is called primary myelofibrosis. It can also develop in people who have polycythaemia vera or thrombocythaemia. This is called secondary myelofibrosis.
This study is for people with either primary or secondary myelofibrosis.
More about this trial
There are a number of different treatments for myelofibrosis. These might include targeted drugs such as ruxolitinib, low dose chemotherapy or 
It is usual to have ruxolitinib to improve the symptoms of myelofibrosis. This might include an enlarged . But sometimes it doesn’t work or it stops working. So researchers are looking at having it with another drug called navitoclax. Doctors think it will improve treatment but they aren’t sure so want to find out more.
Navitoclax blocks the functions of a protein found in myelofibrosis cells. This causes these abnormal cells to die.
In this study some people have navitoclax and ruxolitinib. And some have usual treatment. Your doctor decides on the best available treatment for you. This includes ruxolitinib, hydrocarbamide (hydroxyurea) or pegylated interferon-alpha.
The main aims of this study are to:
- find out how well navitoclax and ruxolitinib work compared to usual treatment
- learn more about the side effects
- find out how treatment affects
quality of life
Who can enter
The following bullet points are a summary of the entry conditions for this study. Talk to your doctor or the study 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 this study if all of the following apply. You:
- have either primary or secondary myelofibrosis that is classed as intermediate or high risk and is causing symptoms
- have at least 2 symptoms of myelofibrosis that are mild to moderate. For example, tiredness, tummy pain or itching. The team can tell you more about these symptoms.
- are having ruxolitinib or a similar drug or you have had this type of treatment in the past but it stopped working. The doctors check when you stopped treatment and the symptoms you have to make sure you are suitable to take part.
- have an enlarged
spleen that your doctor can feel when they examine you - have satisfactory blood test results
- you are up and about more than half the day, you can look after yourself but can't work (performance status 0, 1 or 2)
- have had recent chemotherapy, radiotherapy or
hormone therapy - are willing to use reliable contraception during the study and for a period after
- can complete some forms about how you are feeling for 4 days out of 7 before you are put into a treatment group
- are at least 18 years old
Who can’t take part
Myelofibrosis or cancer related
You cannot join this study if any of these apply. You:
- have already had certain treatments for myelofibrosis. Your doctor checks this to see if you are suitable for this study.
- have had another cancer within 2 years of joining the study. This is apart from carcinoma in situ (
CIS ), of the cervix, food pipe or stomach, non melanoma skin cancer or prostate cancer that isn’t causing symptoms or has spread - have had an experimental treatment in the last month
- are suitable to have
stem cell transplant - have myelofibrosis that has developed into acute myeloid leukaemia (AML). Your doctor will know this.
Medical conditions
You cannot join this study if any of these apply. You:
- have had problems with bleeding or take medication that can affect how your blood clots. You may be able to take certain medications such as low dose aspirin.
- have had radiotherapy to your spleen or you have had your spleen removed
- have HIV, active hepatitis B or hepatitis C or an infection that needs treatment such as an active COVID 19 infection
- have
heart problems . The study team check this. - are taking medication that affects the CYP enzymes
- have had any
biological therapy in the last month or during treatment with navitoclax or ruxolitinib. Your doctor can tell you more.
Other
You cannot join this study if any of these apply. You:
- are pregnant, breastfeeding or planning to become pregnant
- have had a
live vaccine in the last month - are allergic to any of the treatments in the study or anything they contain
Trial design
This phase 3 study is taking place worldwide. The team need to find 330 people to take part including 16 from the UK.
It is a randomised trial. You are put into a group by a computer. Neither you nor your doctor will be able to decide which group you are in. There are 2 treatment groups.
You have 1 of the following:
- ruxolitinib and navitoclax
- usual treatment
Ruxolitinib and navitoclax
Ruxolitinib and navitoclax are tablets.
You take ruxolitinib twice a day, every day.
You take navitoclax once a day, every day.
Your doctor decides on the starting dose. This may be increased or decreased depending on how it is working and any side effects you may have.
You have treatment for as long as it is working and the side effects aren’t too bad.
Usual treatment
You have 1 of the following drugs:
Ruxolitinib is a tablet.
Hydroxyurea (hydrocarbamide) is a type of chemotherapy. You have it as a capsule.
Interferon is a drug that boosts the . Pegylated interferon (pegIFN) is a type of interferon that is designed to stay in the body longer. You have it as an injection under the skin.
Your doctor decides which treatment you have. They can tell you more about each treatment and how often you have it.
Samples for research
You give some extra blood samples during treatment. You give the samples at specific times and the study team will give you more information about this. You also give samples.
The team plan to use the samples to:
- look for
biomarkers to see why treatment might work for some and not others - look at pieces of
DNA to understand more about myelofibrosis
You don’t have to agree to give all the samples if you don’t want to. It won’t affect you taking part in the rest of the study.
Quality of life
The study team ask you to fill out questionnaires
- before you start treatment
- at set times during treatment
The questionnaires ask about side effects and how you’ve been feeling. This is called a quality of life study. You complete these on an electronic device like an I-pad.
Medication diary
You fill in a diary if you are in the group having ruxolitinib and navitoclax. The team give you the diary to complete at home. You do this for the first 5 weeks of the study. You record when you have your medication and how much you take. You must bring the diary with you to all hospital appointments.
Hospital visits
You see the doctor and have tests before you can take part. These include:
- blood tests
- a
physical examination - heart trace (
ECG ) - bone marrow test
- CT scan or MRI scan
- tuberculosis (TB) test. This is either a blood test or a skin test.
You see the doctor for a check up and blood tests:
- every week or 2 for 3 months and then
- once a month for the next 4 months and then
- every 3 months after that
You have a bone marrow test every 6 months.
You stop treatment if your myelofibrosis gets worse. Your doctor will discuss other treatment options with you. You see the study team a month later for a check up.
You have check ups and regular MRI scans if you stopped treatment but your myelofibrosis hasn’t got worse. You see the study doctor every 3 months until your myelofibrosis gets worse or you start another treatment.
The study team then follow you every 2 months up for 5 years. They might see you at a routine hospital appointment, phone you, or check your medical notes to see how you are getting on.
Side effects
The study 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.
The most common side effects of navitoclax include:
- diarrhoea
- feeling or being sick
- an increased risk of bleeding and bruising
- loss of appetite
- feeling tired (fatigue)
- an increased risk of infection
The most common side effects of ruxolitinib are:
- high levels of cholesterol or fat in the blood
- liver changes
- dizziness
- headaches
- weight gain
- high blood pressure
- changes to blood tests that show how the
pancreas is working - an increased risk of bruising or bleeding
- constipation
The study doctor will talk to you about all the possible side effects of treatment. You’ll have a chance to ask any questions you may have.
We have more information about:
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
Dr Claire Harrison
Supported by
AbbVie
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
