A trial of ibrutinib with rituximab and either CHOP or bendamustine for low grade non Hodgkin lymphoma (SELENE)

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

Cancer type:

Blood cancers

Low grade lymphoma

Lymphoma

Non-Hodgkin lymphoma

Status:

Closed

Phase:

Phase 3

This trial is looking at a drug called ibrutinib alongside chemotherapy and rituximab for low grade lymphoma that has got worse or come back despite having other treatment.

Certain types of non Hodgkin lymphoma are slow growing. They are called low grade or indolent lymphoma.

Doctors can treat low grade lymphoma with chemotherapy. You may also have rituximab, which is a type of drug called a monoclonal antibody.

If your lymphoma comes back, you will need to have more treatment. The treatment you have at this time will depend on the first treatment you had. But you may have a combination of chemotherapy and rituximab. In this trial, researchers want to see if adding another drug called ibrutinib helps people in this situation.

Ibrutinib is a type of biological therapy. It is a cancer growth blocker. It stops signals that cancer cells use to divide and grow.

Everybody taking part in the trial has chemotherapy (either bendamustine or CHOP) and rituximab. The type of chemotherapy you have will depend on which treatment you’ve had in the past. Some people will also have ibrutinib, some will have a dummy drug (placebo Open a glossary item ).

The aim of the trial is to see if adding ibrutinib to chemotherapy and rituximab helps people with low grade lymphoma that has come back despite having other treatment.

Who can enter

You may be able to join this trial if all of the following apply. You

Have a low grade lymphoma (either marginal zone lymphoma or follicular lymphoma that is grade 1, 2 or 3A)
Have already had treatment that included chemotherapy and a monoclonal antibody that targets a protein called CD20 (such as rituximab)
Have at least one area of lymphoma that can be seen on scan and measures at least 1cm in size
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 reliable contraception during the trial and for at least a year afterwards if there is any chance you or your partner could become pregnant

You cannot join this trial if any of these apply. You

Have lymphoma in your brain or spinal cord (your central nervous system)
Have already had ibrutinib or a similar drug (the trial team can advise you about this)
Have had chemotherapy in the last 3 weeks (6 weeks if you had a drug called a nitrosourea )
Have had another monoclonal antibody in the last 4 weeks
Have had an antibody that carries a drug or radiation in the last 10 weeks
Have had radiotherapy or another experimental drug in the last 3 weeks
Have had major surgery in the last 4 weeks
Have had a stem cell transplant using cells from a donor
Have already had a chemotherapy drug called an anthracycline and either the last chemotherapy treatment you had included bendamustine, or your lymphoma didn’t respond to bendamustine in the past
Have had any other cancer in the last 3 years apart from very early stage cancer (carcinoma in situ ), non melanoma skin cancer or a type of melanoma called lentigo maligna that was successfully treated
Have had a stroke or bleeding into your brain in the last 6 months
Have had a heart attack in the last 6 months or have certain other heart problems (the trial team can advise you about this)
Need to take drugs such as warfarin to thin your blood
Need to take any drugs that have a strong effect on body substances called cytochrome P (CYP) enzymes
Have had a live vaccine in the last 4 weeks
Have an infection that cannot be controlled with medication
Are known to be HIV, hepatitis B or hepatitis C positive
Are known to be very sensitive to anything in rituximab, or to drugs made in a similar way
Have any other medical condition that the trial team think would affect your taking part
Are pregnant or breastfeeding

Trial design

This is an international phase 3 trial. The researchers need about 400 people to take part.

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. And neither of you will know which group you are in. This is called a double blind trial.

Everybody taking part has chemotherapy (either bendamustine or CHOP) and rituximab. The type of chemotherapy you have in the trial will depend on which treatment you’ve had in the past.

Half the people taking part will also have ibrutinib. The other half will have a dummy drug (placebo Open a glossary item ).

SELENE trial diagram

If you have bendamustine chemotherapy, you have it through a drip into a vein on 2 days every 4 weeks. Each 4 week period is called a cycle of treatment. You have rituximab through a drip into a vein on the first day of each cycle of treatment.

If you have CHOP chemotherapy, a cycle of treatment takes 3 weeks. You have the drugs cyclophosphamide, doxorubicin and vincristine through a drip into a vein every 3 weeks. You also take prednisolone tablets for 5 days. You have rituximab through a drip into a vein on the first day of each treatment cycle.

Whichever type of chemotherapy you have, as long as you don’t have bad side effects, you can have up to 6 cycles of treatment.

Ibrutinib (or the dummy drug) comes in capsules that you swallow. You take 4 capsules once every day. You continue taking ibrutinib (or the dummy capsules) on their own after you finish your chemotherapy. You can carry on taking them until your lymphoma starts to get worse.

The trial team will ask you to fill out a questionnaire at the beginning of the 1st and 6th treatment cycles, and then every 6 months. The questionnaire will ask about side effects and how you’ve been feeling. This is called a quality of life study.

They will also ask you to keep a diary card at home. In this, you write down when you take your capsules. You must take the diary to each hospital appointment.

Hospital visits

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

Physical examination
Blood tests
Heart trace (ECG )
CT scan
PET scan
Bone marrow test (unless you’ve had on in the last 2 months)
Heart scan (echocardiogram or MUGA scan )

You may also need to have an MRI scan.

How often you go to hospital for treatment will depend on the type of chemotherapy you are having. When you have finished your chemotherapy but are still taking the capsules, you go to hospital once every 8 weeks.

You have regular blood tests during treatment. You may need to have more ECGs. You have a CT scan after 3 months, 6 months and then every 4 months for up to 3 years. After 3 years, you have a CT scan every 6 months until your lymphoma starts to get worse or the study has completely finished.

You will have another PET scan if your doctor thinks your lymphoma has completely disappeared.

When you finish treatment, you see the trial team again within a month. They will then check how you are every 3 months for 3 years and then every 6 months after that. This may be at hospital appointments, or they may contact you by phone.

Side effects

As ibrutinib 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

Diarrhoea
Tiredness (fatigue)
Feeling or being sick
Infections
Cough
Swollen hands or feet
Rash
Colds
High temperature (fever)
Dizziness
Constipation
Aching joints or muscles
Bruises
Headaches
Shortness of breath
Loss of appetite
Tummy (abdominal) pain
Indigestion or heartburn
A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
Sore mouth
Headache
Dehydration
Pain in your back, arms or legs
Feeling weak
Nosebleed