A trial of plitidepsin with dexamethasone for myeloma that has come back or is no longer responding to treatment (ADMYRE)

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

Cancer type:

Blood cancers

Myeloma

Status:

Closed

Phase:

Phase 3

This trial is looking at dexamethasone and plitidepsin for myeloma that is not responding to treatment or has come back after other types of treatment. You may hear this called refractory or relapsed myeloma.

Doctors can treat myeloma with chemotherapy, biological therapy and steroids. Some people have intensive treatment and a stem cell transplant.

If myeloma comes back after treatment, doctors may suggest different combinations of drugs. But if you have had a number of different types of treatment, it becomes more difficult to treat myeloma. You may have steroids, but researchers are looking for other treatments to help people in this situation.

In this trial, they are looking at a new drug called plitidepsin (also known as Aplidin). Like other types of chemotherapy plitidepsin damages cells as they divide, which can lead to the death of myeloma cells.

But plitidepsin also seems to have an effect on a growth factor called vascular endothelial growth factor (VEGF Open a glossary item ). Cancer cells need their own blood supply to grow and VEGF helps new blood vessels develop. Blocking the development of new blood vessels can stop myeloma cells growing.

Everybody taking part in this trial will have the steroid drug dexamethasone. Some people will also have plitidepsin. The aims of the study are to

See if plitidepsin and dexamethasone help people with relapsed or refractory myeloma more than dexamethasone alone
Learn more about the side effects

Who can enter

You can enter this trial if you

Have been diagnosed with myeloma that has got worse despite having between 3 and 6 other types of treatment
Have already had the drugs bortezomib and lenalidomide (thalidomide if lenalidomide was not available) unless you were not able to tolerate them
Have satisfactory blood test results
Have recovered from the side effects of any other treatment (apart from hair loss) unless they are very mild
Are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
Are willing to use reliable contraception during the trial and for 6 months afterwards if there is any chance you or your partner could become pregnant
Are at least 18 years old

You cannot enter this trial if you

Have high levels of calcium in your blood (hypercalcaemia) that cannot be controlled
Have had any other treatment in the last 2 weeks that could affect your myeloma, or in the last 6 weeks if treatment included one of a group of drugs called nitrosoureas
Are known to be sensitive to either of the drugs in this trial
Have had chemotherapy that has damaged your bone marrow so that it is not producing enough healthy blood cells
Have muscle weakness (myopathy)
Have had a heart attack or have any other heart problems that are a cause for concern (the trial doctors can advise you on this)
Have had a peptic ulcer or any bleeding from the upper part of your digestive system in the last year or that was related to taking steroids
Have an infection that cannot be controlled with medication or any other medical condition that the trial doctors think could make it unsafe for you to take part
Had mood changes when you took steroids in the past
Are known to be HIV positive or have hepatitis B or C
Are pregnant or breastfeeding

Trial design

This is an international phase 3 trial that will recruit about 250 people. It is a randomised trial. The people taking part are put into treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in.

Everybody taking part has 4 week cycles of treatment.

People in group A have dexamethasone once a week and plitidepsin once every 2 weeks. Dexamethasone is a steroid tablet that you swallow. Plitidepsin is a drug you have through a drip into a vein. It takes about 3 hours each time. You must have the dexamethasone at least an hour before the plitidepsin.

People in group B just take the dexamethasone tablets once a week.

There will be twice as many people in group A as in group B. So 2 out of 3 people entering this trial will get the trial drug.

As long as you don’t have bad side effects, you can carry on having the trial treatment for as long as it controls your disease. If you are in group B and your myeloma has got worse 8 weeks after starting this treatment, the trial doctor may ask you to change to group A.

Hospital visits

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

Physical examination
Blood and urine tests
Heart trace (ECG )
Heart ultrasound (echocardiogram ) or MUGA scan
CT scan or MRI scan
Bone marrow test
X-rays of your bones

You see the trial doctors at the beginning of each treatment cycle and have more blood and urine tests. You have an ECG every 2 weeks and an echocardiogram or MUGA scan every 12 weeks. You may need to have more scans and X-rays.

In the first 2 treatment cycles, some people in group A will have a number of extra blood tests before and after they have plitidepsin. This is to learn more about what happens to drug in the body (pharmacokinetics Open a glossary item ).

After you finish treatment, you see the trial team again about a month later (or earlier than this if you are going to start another type of cancer treatment). You have more blood and urine tests, an ECG and an echo or MUGA scan. You may also have another bone marrow test and another scan or X-ray.

You will then have follow up hospital appointments once a month until your myeloma gets worse or you start another type of treatment. After that, you will see the trial team every 3 months until the trial has completely finished.

Side effects

As plitidepsin is still quite a new drug, there may be some side effects we don’t know about yet. From earlier studies, doctors know the possible side effects include