A trial of panobinostat with bortezomib and dexamethasone for myeloma that has come back or is no longer responding to treatment

Please note this trial is no longer recruiting patients.

This trial is looking at 3 drugs called bortezomib, panobinostat and dexamethasone for myeloma that has come back or stopped responding to treatment.

Doctors usually treat myeloma with chemotherapy and this can get the cancer under control (into remission). But the treatment may stop working and myeloma can come back.

If this happens, you may have a drug called bortezomib (also known as Velcade). Bortezomib is a type of biological therapy called a proteasome inhibitor. Proteasomes are in all cells. They help to break down proteins that the cell doesn’t need. If the proteasomes are blocked, the proteins build up in the cell. The cell then dies.

Bortezomib is currently used on its own to treat myeloma that has come back after chemotherapy. People taking part in this trial will have it with a steroid called dexamethasone. Some people will also have a drug called panobinostat.

Panobinostat (also known as LBH589) is a drug that blocks enzymes called deacetylases (pronounced dee-ass-et-isle-azes). Cells need these enzymes to grow and divide. Blocking them may stop cancer growing.

The aims of this trial are to

See if adding panobinostat to bortezomib and dexamethasone helps people with myeloma that has come back or stopped responding to treatment
Learn more about the side effects of this drug combination

Recruitment

Start 29/04/2010

End 31/03/2012

Phase

Phase 3

Who can enter

You can enter this trial if you

Have myeloma that has got worse during treatment or has come back after treatment
Have already had between 1 and 3 different types of treatment for myeloma
Are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
Have satisfactory blood test results
Are willing to use 2 reliable methods of contraception during the trial and for 3 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 myeloma that has got worse during all other types of treatment
Have already had bortezomib and your myeloma got worse while you were having it, or came back less than 2 months after you finished the treatment
Are currently having any other type of cancer treatment
Have had radiotherapy in the last 4 weeks, or in the last 2 weeks if it was to just a small area of your body
Have had major surgery in the last 2 weeks, or have not recovered from earlier surgery
Have had any other treatment for myeloma in the last 3 weeks
Have already had panobinostat or another drug that blocks enzymes called deacetylases
Have had another experimental drug as part of a clinical trial, or any other type of biological therapy in the last 4 weeks
Have had a stem cell transplant and you have graft versus host disease that needs treatment with steroids
Have not recovered from the side effects of any other treatment unless they are mild
Have had another type of cancer in the last 3 years
Already have damage to the nerves in your hands or feet (peripheral neuropathy) unless it is very mild
Cannot take bortezomib or dexamethasone
Take an epilepsy drug called valproic acid and you would be unable to stop it at least 5 days before starting the study drug (it is very important that you don’t stop taking this type of medication without talking to your doctor)
Have had a heart attack or heart pain (angina) in the last 6 months, have other heart problems that are a cause for concern, or take medication that could affect your heart (your doctor can advise you about this)
Have any signs of bleeding problems
Cannot swallow or absorb tablets for any reason, including diarrhoea or sickness that cannot be controlled with medication
Have any other medical condition that could affect you taking part in the trial
Are known to be HIV, hepatitis B or hepatitis C positive
Are pregnant or breastfeeding

Trial design

This international trial will recruit about 700 people in a number of different countries. 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. You will not know which group you are in either. This is called a double blind trial.

You have 3 week cycles of treatment. Everybody taking part will have bortezomib and dexamethasone. You have bortezomib as an injection into a vein twice a week for the first 2 weeks of each treatment cycle. You take dexamethasone tablets for 2 days each time you have bortezomib.

People in group 1 take panobinostat tablets 3 days a week for the first 2 weeks of each cycle. People in group 2 will take dummy tablets (placebos) in exactly the same way. You don’t have any treatment in the 3rd week of each treatment cycle.

You have 8 cycles of treatment, lasting almost 6 months. If the treatment is helping you, you may go on to have another 4 cycles of treatment. But these cycles will be 6 weeks long, so could take nearly another 6 months.

You will be asked to fill out a questionnaire before you start treatment, every 6 weeks during treatment and when you finish treatment. The questionnaire will ask about any side effects you have had and about how you have been feeling. This is called a quality of life study.

The trial team may ask you to take part in an extra study looking for biomarkers. These are substances that can be measured in the body and show how a disease is developing or how a treatment is working. If you agree to take part, the researchers will keep a sample of the bone marrow taken when you have a bone marrow test at the beginning of the trial. If you have a good response to the treatment, they will ask you to have another bone marrow test.

Hospital visits

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

Physical examination
Blood and urine tests
Heart trace (ECG)
Heart ultrasound (echocardiogram) or MUGA scan
Bone marrow test
CT scan or MRI scan

During the treatment, you have a number of ECGs to see if panobinostat has any effect on your heart. You will also have regular blood tests. And you may need to have more scans.

You go to hospital

3 times in the first week of treatment
Twice in the 2nd week
Then 4 times in each treatment cycle

When you finish treatment, you go back to see the trial doctors, have more blood tests, ECGs and a scan.

If you stop taking panobinostat for any reason other than your myeloma getting worse, the trial team will continue to monitor your progress until your myeloma does get worse or you start another treatment. They will ask if they can contact you at least every 3 months to see how you are.

Side effects

As panobinostat is a new drug, there may be side effects that we don’t know about yet. Possible side effects include

A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
Feeling or being sick
Diarrhoea
Loss of appetite
Tiredness (fatigue)

Panobinostat can also cause changes to your blood sugar levels, the way your thyroid gland works, and the electrical rhythm of your heart. The trial team will keep a close eye on this during your treatment. If you have side effects, they can reduce the dose of panobinostat you take.

During the trial, you must not take certain drugs that can change the rhythm of your heart or affect body substances called CYP enzymes because they can affect how panobinostat works. The trial doctors will advise you about this.

The possible side of bortezomib include