A study looking at a drug called INCB057643 for cancers affecting the bone marrow

Cancer type:

Blood cancers

Myelodysplastic syndrome (MDS)

Myelofibrosis

Polycythaemia

Thrombocythaemia

Status:

Open

Phase:

Phase 1

This study is looking at a new drug called INCB057643 to treat cancers that affect how well the bone marrow works.

It is open to people who have:

myelofibrosis
features of myelodysplastic syndrome and myeloproliferative neoplasm when diagnosed. This is myelodysplastic/myeloproliferative overlap syndrome.
myelodysplastic syndrome
essential thrombocythaemia

More about this trial

INCB057643 is a targeted drug Open a glossary item called a cancer growth inhibitor. It works by blocking a protein called BET. Blocking BET could stop the cancer cells growing.

To find out if INCB057643 can help fight these cancers researchers need to do a large clinical trial Open a glossary item . Before doing this they need to find out what is the best dose for people to take. The best dose is one that helps the most and has the fewest side effects.

There are 2 parts to this study. In the 2nd part some people with myelofibrosis take INCB057643 with ruxolitinib.

The aims of this study are to find:

what is the best dose of INCB057643
out more about the side effects taken by itself and with ruxolitinib
out how acceptable it is to take by itself and with ruxolitinib

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 you have one of the following:

myelofibrosis
myelodysplastic/myeloproliferative overlap syndrome
myelodysplastic syndrome
essential thrombocythaemia

And all of the following apply.

You had at least 1 course of treatment for your condition.
Your cancer continued to grow, came back, you couldn’t continue with treatment due to bad side effects or there isn't any other available treatment that might help.
If you have myelofibrosis you had a drug that stops the JAK2 gene such as ruxolitinib. Or you have taken ruxolitinib for at least the past 8 weeks and the dose has been the same.
You are up and about for at least half the day but might not be able to work (performance status 0, 1 or 2).
You are willing to have a bone marrow tests and there is a previous sample of tissue (biopsy ) that the study team can access.
You have satisfactory blood test results.
You are willing to use reliable contraception during treatment and for a period of time after if there is any chance you or your partner could become pregnant.
You are at least 18 years old.

Who can’t take part

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

are able to have treatment with the aim to cure such as a stem cell transplant
are having a targeted drug that stops the BET gene. You might be able to join part 1 of the study if you have had this type of drug. Your doctor will know more about this.
had another cancer treatment within a certain time period before starting the study treatment. Your doctor will know how long this is for the different treatments.
are having another cancer treatment. This is apart from a small dose of steroids.
had a stem cell transplant from a donor (allogeneic) within 6 months of taking part
had a stem cell transplant of your own cells (autologous) within 3 months of taking part
have graft versus host disease (GvHD)
are taking medication that damps down your immune system . This after a stem cell transplant and within 2 weeks of starting study treatment.
have ongoing side effects from previous treatment. This is unless they are mild, stable and not expected to get any better.
have another cancer that is getting worse or needs treatment. This is apart from certain ones such as non melanoma skin cancer , in situ cancer of the cervix and some others. Your doctor will know about this.

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

have problems with your digestive system such as bleeding, an ulcer, diarrhoea or inflammation of the bowel. Your doctor will know more about this.
have had a heart attack, chest pain (angina) or another heart problem .
have an infection that needs treatment
have HIV, hepatitis B or hepatitis C
are taking certain medications such as ones that thin your blood or affect the CYP enzymes. Your doctor will know which medications these are.
have not recovered from any major surgery you might have had
have a disorder that can cause bleeding problems. Or you are at a high risk of bleeding.
have any other medical condition or mental health problem that your doctor thinks will affect you taking part

Other
You cannot join this study if any of these apply. You are:

allergic or very sensitive to INCB057643 or any of its ingredients
pregnant or breastfeeding

Trial design

This is a phase 1 study. The team need about 39 people to take part. There are 2 parts to the study.

In part 1 the team want to find the best dose of INCB057643. This is one that helps the most and has the fewest side effects.

The first people in this part take a small dose of INCB057643. If that goes well then the next people take a higher dose. And so on until the team find the best dose of INCB057643.

For people with myelofibrosis 8 days after starting treatment you go in to the clinic. You take your tablets when you are in the clinic. You must not eat or drink (fast) before you come in to the clinic. This is for a blood test that the team take before you have your tablets.

Part 2 is for people with myelofibrosis only. There are 2 groups. Your doctor will tell you which group you are in.

People in group A have INCB057643 by itself.

People in group B have INCB056743 with ruxolitinib. You continue taking ruxolitinib as you did before taking part in the study.

For people in group B 8 days after starting treatment you go in to the clinic. You take your INCB056743 tablets and ruxolitinib when you are in the clinic. You must not eat or drink (fast) before you come in to the clinic. This is for a blood test that the team take before you have your tablets.

INCB056743 is a tablet. You take it in the morning. You can take it with or without food. Your doctor will tell you how many to take.

You continue treatment for as long as it is helping. And the side effects aren’t too bad.

Quality of life
This is only for people who have myelofibrosis. You fill in a few questionnaires a number of times during the study. The questions ask about:

your general health
what you are able to do
side effects and symptoms

These are quality of life questionnaires.

Samples for research
You give bone marrow samples Open a glossary item and blood samples. The team use these to find out:

what happens to INCB056743 in the body
how it affects the body
about the genes that might control or affect the development of cancer
more about substances (biomarkers ) that might show how well treatment is working

Hospital visits

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

a physical examination
blood tests
urine test
heart scan (ECHO or MUGA )
heart trace (ECG )
bone marrow test
CT scan or MRI scan

You see the doctor regularly while having treatment for blood tests and to see how you are.

You have a bone marrow test every 24 weeks and a scan every 12 weeks.

You see the doctor at the end of treatment and then about a month after.

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.

INCB057643 is a new drug and there might be side effects we don’t know about yet. The most common side effects we do know are:

feeling or being sick
tiredness (fatigue)
loss of appetite and changes to taste
a drop in blood cells causing shortness of breath and an increased risk of bruising and bleeding
diarrhoea or constipation
a high level of sugar in the blood
difficulty breathing
not enough fluid in the body (dehydration)
cough
dizziness
high temperature (fever)
acute kidney injury
dry mouth