A trial of navitoclax with ruxolitinib for myelofibrosis (TRANSFORM 1)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:





Phase 3

This trial is combining navitoclax with ruxolitinib for myelofibrosis.

It is open to people who:

  • have intermediate 2 or high risk myelofibrosis and 
  • have not had a JAK2 inhibitor drug such as ruxolitinib 

More about this trial

Myelofibrosis is a myeloproliferative neoplasm Open a glossary item. It is a rare cancer that causes scarring of the bone marrow Open a glossary item. This makes it difficult for the bone marrow to produce blood cells. 

Ruxolitinib is a standard treatment Open a glossary item for myelofibrosis. It is a targeted drug Open a glossary item called a cancer growth blocker. It blocks a gene Open a glossary item called JAK2. By blocking JAK2 ruxolitinib slows down or stops the cancer cells growing and dividing.  

Navitoclax is a targeted drug. It works by blocking proteins called BCL-2. Cancer cells need these proteins to stay alive. By blocking BCL-2 proteins navitoclax can cause the death of cancer cells.

Researchers think that combining navitoclax with ruxolitinib will help people with myelofibrosis. In this trial half the people have navitoclax and ruxolitinib. The other half have ruxolitinib and a dummy drug (placebo Open a glossary item).

The aims of this trial are to find out:

  • how well navitoclax with ruxolitinib works for myelofibrosis
  • what the side effects of this combination are
  • how it affects quality of life Open a glossary item

Who can enter

The following bullet points are a summary of 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 this trial if all of the following apply. You:

  • have intermediate 2 risk or high risk myelofibrosis. Your doctor will know what your risk group is.
  • can fill in a form that scores your symptoms on at least 4 out of 7 days before you go into a treatment group (randomised Open a glossary item). And you have at least 2 symptoms that score 3 or more, or the total score of your symptoms is 12 or more. 
  • have an enlarged spleen Open a glossary item
  • have satisfactory blood test results
  • have had a skin test for tuberculosis (TB). The result shows you don’t have or are unlikely to have TB. 
  • have a heart trace (ECG Open a glossary item) that shows your heartbeat is satisfactory. Your doctor will test for this. 
  • can look after yourself but might not be able to do heavy physical work (performance status 0, 1 or 2)
  • are willing to use contraception during treatment and for a time after if there is any chance you or your partner could become pregnant
  • are at least 18 years old

Who can’t take part

Cancer related
You cannot join this trial if any of these apply. You:

  • can have a stem cell transplant Open a glossary item or you have had a stem cell transplant using your own stem cells
  • have already had treatment with a JAK2 inhibitor such as ruxolitinib. Your doctor will know this. 
  • have a blood test or bone marrow test that shows your myelofibrosis has changed into leukaemia Open a glossary item
  • have chemotherapy, radiotherapy or hormone therapy within 30 days of starting the trial treatment. For certain medications such as hydroxyurea that help reduce the signs and symptoms of myelofibrosis it is 7 days. Your doctor will know which drugs these are. 
  • have had a targeted drug Open a glossary item or an immunotherapy drug Open a glossary item such as interferon within 30 days of starting trial treatment or you might need to have it during the trial
  • have had a drug that works the same as or in a similar way to navitoclax. Your doctor will know this. 
  • had another cancer within the past 2 years. That is apart from successfully treated non melanoma skin cancer, Open a glossary item in situ carcinoma Open a glossary item of the cervix, food pipe (oesophagus) or stomach, or prostate cancer that has no symptoms, hasn’t spread and doesn’t need treatment. 

Medical conditions
You cannot join this trial if any of these apply. You:

  • have HIV, hepatitis B, hepatitis C
  • have an ongoing infection or have a low number of white blood cells and a high temperature
  • have signs or symptoms of COVID-19 or you have been in contact with someone who has COVID-19 in the past 2 weeks of screening to take part in the trial. You might be able to join the trial after certain conditions are met. Your doctor will know about this.
  • are having medication such as warfarin that thins your blood to prevent clots within 3 days of starting trial treatment or you need to take it during the trial. This is apart from low dose aspirin and low molecular weight heparin. 
  • have had an experimental drug as part of another clinical trial within 30 days of starting the trial treatment
  • are allergic or sensitive to the drugs used in the trial or any of their ingredients
  • have any other medical condition or mental health problem that might affect you taking part

You cannot join this trial if any of these apply. You:

  • have had a live vaccine Open a glossary item within 4 weeks of starting trial treatment or you might need to have a live vaccine during treatment or in the 4 weeks after treatment. The COVID-19 vaccines aren’t live vaccines. 
  • are pregnant or breastfeeding

Trial design

This is an international phase 3 trial. The team need 230 people worldwide to take part with 18 people from the UK.

It is a double blinded randomised trial. There are 2 groups. Neither you nor your doctor can choose which group you are in. Nor will you or your doctor know what treatment you are having. 

During the trial your doctor will be able to find out what treatment you are having if it is necessary to know. 

The 2 groups are:

  • ruxolitinib and navitoclax
  • ruxolitinib and a dummy drug (placebo)

Navitoclax is a tablet. You take it once a day every day. 

The dummy drug is a tablet. You take it once a day every day.

Ruxolitinib is a tablet. You take it twice a day every day. 

You continue with treatment for as long as it is working and the side effects aren’t too bad.  

You have a dosing diary to fill in for the first 5 weeks of treatment. The team give you instructions on how to fill it in and when. 

During treatment there are certain foods, drinks and medications you should avoid having. Your doctor will talk about this with you when you join the trial. 

Quality of life
You fill in a few questionnaires:

  • before you start treatment 
  • during treatment 
  • at the end of treatment

The questions asked are about:

  • signs and symptoms
  • your general health
  • what daily activities you can do 

These are quality of life questionnaires

Research samples
You give blood samples:

  • before starting treatment
  • several times during treatment
  • at the end of treatment

You have a bone marrow test:

  • before starting treatment 
  • a few times during treatment
  • at the end of treatment

Researchers use these samples to find out:

  • what happens to the drugs in the body
  • how treatment affects the body
  • more about myelofibrosis

Hospital visits

You see the doctor to have tests before taking part. These tests include:

You see the doctor at regular times during treatment. This is to see how you are and to have blood tests. 

A month after stopping treatment you see the doctor to see how you are. You then see the doctor every 2 months for up to 5 years or a member of the trial team will phone you. 

You have a bone marrow test during treatment at:

  • week 25
  • week 49
  • week 73

You only then have a bone marrow test if your doctor requests. This could be because they think your cancer is getting worse. 

You have an MRI scan or a CT scan regularly during treatment and then:

  • a month after stopping treatment
  • every 24 weeks for up to 8 years 

During the 8 years you stop having the scans if your cancer gets worse, the cancer becomes a leukaemia or you start a new treatment for your cancer.   

After 24 weeks of treatment if you stop for any other reason than your cancer is getting worse you see the doctor every 12 weeks till your cancer gets worse or changes to leukaemia. 

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. 
The most common side effects of navitoclax include:

We have information about ruxolitinib and its side effects.

Your doctor or a member of the trial team will talk to you about the side effects of the treatments before you agree to take part.

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.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Donald McLornan

Supported by


If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:


Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Last reviewed:

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