A trial of ruxolitinib and sonidegib (LDE225) for myelofibrosis

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

Cancer type:

Blood cancers




Phase 1/2

This trial is looking at ruxolitinib (also known as INC424) and a drug called sonidegib (also known as LDE225) for myelofibrosis.

Myelofibrosis (pronounced my-eh-lo-fy-bro-sis) is a rare blood disorder. It is a condition that causes scarring of the bone marrow Open a glossary item. A small number of people with myelofibrosis go on to develop acute myeloid leukaemia.

Myelofibrosis can develop without having had any other condition. This is called primary myelofibrosis (PMF) or chronic idiopathic myelofibrosis. It can also develop in people who have polycythaemia vera or thrombocythaemia. This is called secondary myelofibrosis.

This trial is for people with either primary or secondary myelofibrosis who also have an enlarged spleen Open a glossary item.

The trial is looking at a combination of 2 drugs called ruxolitinib and sonidegib.  They are both types of biological therapy.

Ruxolitinib is a cancer growth blocker. It stops signals that cancer cells use to divide and grow. Doctors can already use ruxolitinib to treat myelofibrosis.

Sonidegib is a new drug that blocks a specific type of cell signalling called the hedgehog pathway.

The aims of this trial are to

  • Find the highest safe doses of ruxolitinib and sonidegib that you can have at the same time for myelofibrosis
  • See if having these 2 drugs together helps people with myelofibrosis
  • Learn more about the side effects of this drug combination and what happens to the drugs in your body

Who can enter

You may be able to enter this trial if

  • You have either primary or secondary myelofibrosis that is considered to be at least intermediate risk and is causing symptoms
  • Your spleen Open a glossary item is enlarged by at least 5cm
  • You can’t have a stem cell transplant
  • You are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
  • You stopped any other treatment for myelofibrosis at least a week ago
  • You have satisfactory blood test results
  • You are at least 18 years old
  • You are willing to use reliable contraception during the trial and for 20 months afterwards if there is any chance you or your partner could become pregnant

You cannot enter this trial if you

  • Have already had  ruxolitinib or a similar drug – your doctor can advise you about this
  • Have had another experimental drug in the last month, or earlier if there is any chance some of the drug could still be in your body
  • Have had radiotherapy to your spleen in the last year
  • Have had major surgery in the last 2 weeks
  • Have had any type of cancer unless it was a very early stage and was successfully treated at least 3 years ago
  • Have an infection that needs treatment (if you are taking antibiotics you can join the trial once you have finished the course)
  • Have had a heart attack or heart pain (angina) in the last 3 months, or have certain other heart problems – the trial team can advise you about this
  • Take any other medication that can affect how your blood clots (you can take part if you take aspirin, as long as it is a low dose)
  • Have any problem with your digestive system Open a glossary item that could affect how you absorb tablets or capsules
  • Have certain medical conditions or take medication that can affect your muscles – the trial team can advise you about this
  • Are planning to start doing any new physical activity
  • Take any other medication that can affect body substances called cytochrome P (CYP) enzymes – the trial team can advise you about this
  • Are pregnant or breastfeeding

Trial design

This phase 1/2 trial is in 2 parts and will recruit about 80 people all together. Everybody taking part has ruxolitinib and sonidegib.

In part 1, the researchers are looking for the highest safe doses of ruxolitinib and sonidegib that you can have at the same time for myelofibrosis. The first few patients taking part will have low doses of both drugs. If they don’t have any serious side effects, the next few patients will have higher doses. And so on, until they find the best doses to give. This is called a dose escalation study.

In part 2, the researchers want to see how well the treatment works. Everybody joining this part of the trial has the highest safe doses found in part 1 of the trial.

Ruxolitinib is a tablet that you take twice a day. Sonidegib is a capsule that you take once a day. The trial team will give you a diary to keep at home. Each day you write down what time you eat in the morning and when you take the tablets and capsules.

As long as you don’t have any bad side effects and the treatment is helping, you can carry on taking the trial drugs for at least 2 years. After this time if the drugs are helping then you can take part in an extension study. This means you continue to take both drugs but you see the trial team less frequently.

The trial team will ask you to fill out a questionnaire before you start treatment, a number of times during treatment and after you finish treatment. The questionnaire will ask about side effects and how you’ve been feeling.  This is called a quality of life study.

Hospital visits

You see the trial team and have some tests before you start the trial treatment. The tests include

You see the trial team 12 times during the first 3 months of treatment. After that, you see them every 4 weeks for up to 2 years. If you continue treatment for longer than 2 years you see the doctors every 3 months.  You have blood tests at each visit and an ECG at some visits. You may have more scans or X-rays if your doctor thinks they are necessary.

You have a bone marrow test

  • In week 1 of treatment
  • In week 13
  • After 25 weeks of treatment
  • Every 24 weeks until week 97
  • When you finish treatment

When you finish the trial treatment, you will have another hospital visit to have a physical examination, blood tests, a CT or MRI scan and an ECG.  And a member of the trial team will contact you by phone a month later to see how you are.

Side effects

As sonidegib is a new drug, there may be side effects we don’t know about yet. In trials so far, the most common side effects have been

Sonidegib can also affect the way your muscles, kidneys, liver and pancreas work. You will have regular blood tests to monitor for any changes.

The most common side effects of ruxolitinib for people with myelofibrosis include

  • A drop in blood cells causing an increased risk of infection, bruising or bleeding problems, tiredness and breathlessness
  • Bruising
  • Urinary tract infections
  • High levels of cholesterol in your blood Open a glossary item
  • Dizziness
  • Headache
  • Weight gain
  • Changes to the way your liver works

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

Prof Claire Harrison

Supported by

Experimental Cancer Medicine Centre (ECMC)
NIHR Clinical Research Network: Cancer

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

Freephone 0808 800 4040

Last review date

CRUK internal database number:

Oracle - 10980

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

Last reviewed:

Rate this page:

No votes yet
Thank you!
We've recently made some changes to the site, tell us what you think