A trial of dasatinib and BMS-833923 for chronic myeloid leukaemia (CA180323)

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

Cancer type:

Acute leukaemia

Acute lymphoblastic leukaemia (ALL)

Blood cancers

Chronic leukaemia

Chronic myeloid leukaemia (CML)

Leukaemia

Status:

Closed

Phase:

Phase 1

This trial is looking at a combination of dasatinib and a new drug called BMS-833923 (also known as XL139) for Philadelphia positive leukaemia.

Most people with chronic myeloid leukaemia (CML), and some people with other types of leukaemia have an abnormal chromosome Open a glossary item called the Philadelphia chromosome. You may hear this called Philadelphia positive leukaemia.

Doctors can treat Philadelphia positive leukaemia with drugs called tyrosine kinase inhibitors (TKIs). Imatinib, dasatinib and nilotinib are TKIs that doctors may use. These drugs can work well. But sometimes the doctors can still see signs of the leukaemia or the Philadelphia chromosome in your blood or bone marrow Open a glossary item . And sometimes, even though leukaemia may respond well, the drugs then stop working (the leukaemia becomes resistant to them).

In this trial, researchers are looking at a new drug called BMS-833923. It is a type of biological therapy that can block chemical signalling between cells, which may affect their growth. The people taking part have already had imatinib, dasatinib or nilotinib, but their leukaemia has become resistant, or they still have signs of the leukaemia or the Philadelphia chromosome in their blood or bone marrow. They will have a combination of dasatinib and BMS-833923. The aims of the trial are to

Find the highest dose of BMS-833923 you can have alongside dasatinib
Learn more about what happens to the drug in your body

Who can enter

You may be able to enter this trial if you

Have chronic myeloid leukaemia (CML) or acute lymphoblastic leukaemia (ALL) that is Philadelphia positive
Have stopped responding, or are not responding very well to imatinib, dasatinib or nilotinib
Are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
Have satisfactory blood test results
Are at least 18 years old
Are willing to use a reliable form of contraception during the trial and for 3 months afterwards if there is any chance you or your partner could become pregnant

You cannot enter this trial if you

Have had blood or bone marrow tests that show no signs of the Philadelphia chromosome (a cytogenetic response )
Have had a stem cell transplant in the last 6 months
Have had another experimental drug in the last 4 weeks
Have had chemotherapy in the last week
Have not recovered from the side effects of other treatments, unless they are very mild
Have changes (mutations) to genes called T315I or T315A – you can check this with your doctor
Have a build up of fluid around your heart (pericardial effusion ) or around your lungs (pleural effusion )
Have problems with your digestive system that would make it difficult for you to swallow or absorb tablets
Have had problems with blood clots or need to take drugs to prevent blood clots
Have any other type of cancer
Have had pancreatitis in the last 6 months
Are allergic to dasatinib or drugs similar to BMS-833923, or have had very bad side effects from dasatinib
Need to carry on taking any other drugs that can affect your heart rhythm, or affect CYP enzymes (your doctor can advise you about this - it is important that you don’t stop taking any sort of medication before discussing it with your doctor)
Have had a heart attack, heart pain (angina) or heart failure in the last 6 months, or have any other heart problem that is a cause for concern
Have any other serious medical condition that could affect you taking part
Are pregnant or breastfeeding

Trial design

The trial will recruit about 40 people. Everybody taking part will have dasatinib and BMS-833923. The first few patients taking part will have a low dose of BMS-833923. If they don’t have any serious side effects, the next patients will have a higher dose. And so on, until they find the best dose to give. This is called a dose escalation study. The dose of dasatinib you have will depend on the type of leukaemia you have and the phase your leukaemia is in. You take both drugs by mouth.

You take dasatinib capsules once a day. After 4 weeks, you start taking BMS-833923 tablets as well. You take them twice a day for the first week, then once a day after that. Depending on the dose you have, you may take them just once a day from when you start.

As long as you don’t have bad side effects, you can then carry on taking dasatinib and BMS-833923 for as long as this treatment helps you.

During the trial, doctors will test your blood to look for abnormal genes called BCR-ABL, which are created by the Philadelphia chromosome. If they cannot see any signs of these abnormal genes, they say you are in complete molecular remission. If you stay in complete remission for more than a year, you stop taking the drugs. But the trial team will continue to monitor you very closely for up to 2 years. If they see any signs that the leukaemia has come back, you can start taking the study drugs again.

Hospital visits

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

Physical examination
Chest X-ray
Blood tests
Heart trace (ECG )
Heart ultrasound (echocardiogram )
Bone marrow test

Depending on the dose of BMS-833923 you are having, the trial team may ask you to have a skin biopsy Open a glossary item . This is optional. If you don't want to have this biopsy, you don't have to. You can still take part in the trial.

During treatment, you have regular blood tests. On the first day of treatment and on 2 other days during treatment, you have a number of blood tests throughout the day and need to stay at the hospital for at least 8 hours.

You have 3 more chest X-rays, heart scans and ECGs during the first year of treatment. You also have a bone marrow test every 3 months, but this may become less frequent after a year of treatment.

When you finish the treatment, you see the trial doctors and have more blood tests. You will have a bone marrow test if you haven’t had one in the last 3 months. You then see the doctors again 2 months later.

Side effects

As BMS-833923 is a new drug, there may be side effects we don’t know about yet. The possible side effects include

Muscle cramps
Taste changes
Tiredness (fatigue)
Feeling or being sick
Loss of appetite or weight loss
Hair loss
Diarrhoea

The trial team will talk to you about other possible side effects before you agree to join the trial.

The most common side effects of dasatinib include

A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
Feeling or being sick
Diarrhoea
Tummy (abdominal) pain
Headache
Fatigue
A build up of fluid in your body (fluid retention)
Rash
Bone and muscle pain

We have more information about dasatinib in our Cancer drugs section.

You must not eat grapefruit or Seville oranges (or drink their juices) during the trial because they can interact with the trial drugs. And you cannot take some medicines for indigestion (antacids) at the same time as dasatinib – the trial team can advise you about this.