A trial of lenalidomide and rituximab with or without bendamustine for follicular lymphoma (ReBEL)

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 2

This trial is for people with a type of non Hodgkin lymphoma called follicular lymphoma that has come back after treatment (relapsed).

Cancer Research UK supports this trial.

More about this trial

Follicular lymphoma is the second most common type of non Hodgkin lymphoma (NHL). It is a low grade (or slow growing) NHL.

It can be difficult to cure follicular lymphoma, but it is usually possible to control it for a number of years. This is called remission Open a glossary item

After some time, follicular lymphoma is likely to come back. This is a relapse Open a glossary item

and it can be harder to get it under control again. You usually have treatment with chemotherapy or target cancer drugs (biological therapy).

Rituximab (or Mabthera) is a type of biological therapy. It works by sticking to a protein called CD20 on the surface of the lymphoma cells. The immune system Open a glossary item

then picks out the marked cells and kills them.

Lenalidomide (or Revlimid) works in different ways including helping the immune system to target cancer cells. And stopping the cancer developing new blood vessels. It is used as a treatment for a type of blood cancer called multiple myeloma. But doctors know from previous research that it can also help people with follicular lymphoma.

This trial is also looking at a chemotherapy drug called bendamustine (Levact). It works by interfering with the DNA Open a glossary item

in the cancer cell so it can’t divide into 2 new cells.

This trial is in 2 parts. In part 1, the doctors looked for the best dose of lenalidomide, rituximab and bendamustine. This part is now closed and doctors are looking for people to join part 2.

In part 2, people have 1 of the following:

lenalidomide and rituximab
lenalidomide, rituximab and bendamustine

Doctors know that having lenalidomide or rituximab alone can help people with follicular lymphoma. But they want to find out if having it together with bendamustine is better.

The main aims of this trial are to:

learn more about the side effects of treatment
find out which treatment is better at helping people with relapsed follicular lymphoma
look for substances that can tell how a treatment is working

Who can enter

The following bullet points list the entry conditions for this trial. Talk to your doctor or the trial team if you are unsure about any of these. They will be able to advise you.

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

have relapsed follicular lymphoma (grade 1, 2 or 3a)
have follicular lymphoma in more than 1 lymph node (Ann Arbour stage 2 to 4) - your doctor will check for this
have a protein called CD20 on the lymphoma cells – your doctor will check for this
have had up to 5 different combinations of treatments (treatment regimens) that reached your whole body (systemic treatment)
have 1 area of lymphoma that measures at least 2 cm across on a CT scan, or 2 or more areas that measure at least 1½ cm across and you haven’t had radiotherapy to it
have satisfactory blood test results
are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
are at least 18 years old
are willing to use reliable contraception during the trial and for 28 days after the last dose of lenalidomide and 12 months after the last dose of rituximab if there is any change you or your partner could become pregnant

As well as the above, you must also have at least 1 of the following:

you have 3 or more lymph nodes that measure more than 3 cm across
your spleen is enlarged (splenomegaly) and this is causing you problems
you have an area of cancer in your lymph nodes or another organ (except the spleen) that measures more than 7 cm across
you have had a high temperature (fever), night sweats or you have lost a significant amount of weight (more than 10%) in the past 6 months
you have a low count of red blood cells (anaemia ) or platelets (thrombocytopenia)
your follicular lymphoma is pressing on organs nearby and causing you problems (for example, it is pressing on the kidneys and causing a build up of urine inside them - hydronephrosis)
you have a build up of fluid around the lungs (pleural effusion) or the tummy (peritoneal effusion)
your follicular lymphoma has spread to organs outside the lymphatic system (extranodal disease ) and this is causing you problems

You cannot join this trial if any of these apply.

Cancer related

your lymphoma has changed into a high grade type
your lymphoma didn’t get any better when you had rituximab or started getting worse within 6 months of finishing treatment
you have had lenalidomide or any other similar drug
if you have had bendamustine, you must not have had it in the past 18 months, your lymphoma must have got better either a little bit or completely when you took the drug and you must not have had more than 6 treatment cycles
you have had a stem cell transplant using cells from a donor (allogeneic)
you have had a transplant using your own cells (autologous) in the past 12 months
you are having other anti cancer treatments
you have had another cancer in the past 5 years apart from cancer that has not spread (carcinoma in situ ) of the cervix or breast, certain types of prostate cancer, or basal cell cancer or squamous cell skin cancer.

Medical conditions

you take allopurinol
you have HIV
you have hepatitis B or hepatitis C
you have problems with your immune system that cause you to have low levels of red blood cells (autoimmune haemolytic anaemia) or platelets (autoimmune thrombocytopenia)
you have an active infection
you are known to be sensitive or allergic to proteins produced in a laboratory or murine products
you are sensitive or allergic to lenalidomide or similar drugs
you have problems with your thyroid such as hyperthyroidism or hypothyroidism that aren’t controlled with medication
you have moderate or severe problems with your nerves that cause you to have numbness or tingling (neuropathy)
you have heart problems that cause you to have difficulty breathing when you are resting or after a short physical activity
you have lung problems that are causing symptoms
you have problems with your brain, spinal cord or nerves (neurological problems) or a mental illness
you have any other serious medical condition or mental health problem that isn’t controlled by medication

Other

you have had a yellow fever vaccine in the past 4 weeks
you have had an experimental treatment in the past 28 days
you are pregnant or breastfeeding

Trial design

This is an international phase 2 trial. Researchers hope that about 150 people will take part.

This trial is randomised. The people taking part are put into 1 of the following treatment groups by computer:

lenalidomide and rituximab
lenalidomide, rituximab and bendamustine

Neither you nor your doctor will be able to decide which group you are.

Lenalidomide and rituximab

Lenalidomide are capsules you take at home. You have them every day, for 21 days. Then you have a break for 7 days. This is a treatment cycle.

You have rituximab as a drip into a vein or as an injection under your skin (subcutaneous injection). You have it on the 1st day (day 1) of each treatment cycle. It takes a few hours for the drip into your vein and 5 minutes for the injection under your skin.

You continue having treatment for as long as your cancer stays the same and the side effects aren’t too bad. You can have up to 6 treatment cycles (about 6 months).

After 6 treatment cycles you might be able to continue having rituximab alone. This is called rituximab maintenance.

During the rituximab maintenance, you have treatment every 3 months, for up to 2 years. You doctor can tell you more about this.

Lenalidomide, rituximab and bendamustine

You have bendamustine as a drip into your vein. And rituximab as a drip into a vein or as an injection under your skin. You have them on the 1st day of each treatment cycle. This takes a few hours. On the second day (day 2) you just have bendamustine.

You start taking lenalidomide capsules on day 3 of each treatment cycle. You take them every day, for 19 days. Then you have a break for 7 days.

You continue having treatment for as long as your cancer stays the same and the side effects aren’t too bad. You can have up to 6 treatment cycles.

After 6 cycles, you might be able to continue having rituximab alone (rituximab maintenance) for up to 2 years. Your doctor can tell you more about this.

Blood tests

Everyone taking part has some extra blood tests. You have them before the start of treatment and then:

on day 14 of cycle 1
before cycle 2 and cycle 4
at the end of cycle 6
after 1 year of maintenance treatment
at the end of maintenance

The trial team might ask your permission to store your blood samples for up to 15 years and use them in future studies. You don’t have to agree to have your samples stored if you don’t want to. You can still take part in this trial.

Bone marrow and lymph node biopsy

You have a small amount of bone marrow fluid and tissue taken (a bone marrow biopsy Open a glossary item

) as part of this trial.

You have the biopsy before the start of treatment and you might have it again at the end. This is only if the doctors find lymphoma cells in the first biopsy.

You might also have a lymph node biopsy before the start of your treatment.

Doctors use your lymph node and bone marrow samples to confirm your follicular lymphoma diagnose. They will also look for proteins to see if they can tell how the treatment is working.

The researchers will also ask you if they can keep your samples for up to 15 years and use it in future studies. Again, you don’t have to agree to have your samples stored if you don’t want to.

Hospital visits

You see a doctor and have some tests before taking part. These tests might include:

a physical examination
blood tests
urine test
a CT scan
a PET scan
a chest x-ray
a heart trace (ECG )

After you start treatment, you see a doctor and have blood tests twice a week, for the first 2 weeks. Then you see them every week for 6 weeks.

After 6 weeks, you see the doctor and have blood tests once every 2 weeks.

You have a CT scan before the start of treatment. You then have a CT scan:

after 3 treatment cycles
after 6 treatment cycles
once a year during the maintenance treatment
when you finish treatment

You have a PET scan before the start of treatment and after 6 treatment cycles. You may also have a PET scan at the end of treatment. You stop having treatment if your cancer gets worse.

After 6 months, you might continue having rituximab treatment (rituximab maintenance). If you have this, you see a doctor and have blood tests every 3 months. You also have a CT scan every year as part of your follow up.

When you finish your treatment, you see the doctor and have blood tests:

every 3 months for 2 years
then every 6 months for 3 years

Side effects

The trial team monitor you during the time you have treatment and you have a phone number to call them if you are worried about anything. The team will tell you about all the possible side effects before you start the trial.

The most common side effects of lenalidomide are:

a drop in blood cells causing an increased risk of infection, bleeding, tiredness and breathlessness
blood clots
high temperature (fever) and flu like symptoms
dizziness
skin problems such as rash, redness and dry skin
tiredness (fatigue)
pain in your head, chest, muscles, tummy (abdomen), joints, legs, hands and feet
shortness of breath and chest infection
loss of appetite
diarrhoea or constipation
feeling or being sick
eye problems such as blurred vision
changes to your taste
swelling of your arms and legs