A study looking at rituximab, lenalidomide and ibrutinib for diffuse B cell lymphoma

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

Cancer type:

Blood cancers

High grade lymphoma

Lymphoma

Non-Hodgkin lymphoma

Status:

Closed

Phase:

Phase 1/2

It is for people with lymphoma that has come back or continued to grow after their first treatment. And who aren’t suitable for high dose chemotherapy and a stem cell transplant.

More about this trial

Diffuse large B cell lymphoma (DLBCL) is a type of non Hodgkin lymphoma. It is the most common type of high grade non Hodgkin lymphoma.

Chemotherapy and a drug called rituximab are the usual treatments for DLBCL. This works well for many people and gets rid of the lymphoma cells (gets it into remission). But sometimes, the DLBCL doesn’t go away, or it comes back after a short period.

So some people might then have high dose chemotherapy followed by a stem cell transplant. But this isn’t suitable for everyone. So doctors are trying to improve treatment for this group of people.

In this study, they are looking at a new combination of treatments. It includes:

rituximab (a monoclonal antibody )
lenalidomide (helps the immune system target cancer cells)
ibrutinib (a cancer growth blocker)

These are all types of targeted cancer drugs that work in different ways. This study is the first time people with DLBCL are having these 3 drugs together. This study has been ongoing for more than 3 years.

The study is in 2 parts. The first part is complete. It looked at the best dose of treatment. The 2nd part is now open and it is looking at treatment in a larger group of people.

The aims of the study are to:

find out how well the treatment works
learn more about the side effects
find out what happens to the drugs in the body

Who can enter

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

Who can take part

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

You:

have diffuse B cell lymphoma that came back after your last treatment or the last treatment you had stopped working
have a sample of the lymphoma available for the study team to do some tests
have a sub type of DLBCL called non GCB
had a suitable first treatment for the lymphoma such as chemotherapy and rituximab (R-CHOP)
had an abnormal scan result and if the doctors were uncertain that the lymphoma had come back, you gave a tissue sample to confirm it had
haven’t had high dose chemotherapy and a stem cell transplant and this was because any of the following apply:

o you are 70 years or older

o you have problems with your heart or lungs

o you have severe problems with other organs in the body

o you don’t want this treatment

o treatment hasn’t worked so far
have lymphoma that can be measured on a scan and measures more than 1.5 cm across
are well enough to be up and about and carry out light work (performance status 0 or 1)
have satisfactory blood, liver and kidney test results
are willing to use reliable contraception during the study and for up to 3 months afterwards, if you are a man and for up to 12 months afterwards if you are a woman
are willing to use reliable contraception if you are male even if you have had a vasectomy if there is any chance your partner could become pregnant
have a negative pregnancy test within 10 to 14 days of starting lenalidomide if there is any chance you could become pregnant and you are willing to have ongoing pregnancy tests
are willing to have regular counselling about the risks of becoming pregnant while taking lenalidomide
are at least 18 years old

Who can’t take part

You cannot join this study if any of these apply.

Lymphoma or cancer related

You:

have lymphoma that has changed from low grade to high grade (transformed), is germinal center DLBCL or you have DLBCL mixed with follicular or MALT lymphoma
have lymphoma that started in the chest (primary mediastinal lymphoma)
have lymphoma in the brain or spinal cord
have had a transplant with someone else’s stem cells or you have had an organ transplant
have had chemotherapy, radiotherapy, or a cancer antibody and there hasn’t been a 2 week period for these drugs to clear your body before starting study treatment
are having experimental treatment as part of a clinical trial
have had ibrutinib, lenalidomide, or both in the past
have had a monoclonal antibody that has a radioactive substance attached to it, such as ibritumomab, within 10 weeks of starting study treatment
are willing to use reliable contraception during the study and for up to 3 months afterwards if you are a man and for up to 12 months afterwards if you are a woman
have had any other cancer in the last 5 years apart from carcinoma in situ , basal cell or squamous cell skin cancer that has been successfully treated

Medical conditions

You:

have taken medication that dampens down the immune system in the 28 days before starting study treatment
have had a recent infection and you needed antibiotics as a drip into a vein within14 days of starting study treatment
have side effects from past treatments unless they are mild
have a bleeding condition such as von Willebrand disease or haemophilia
have had major surgery within 4 weeks of starting study treatment
can’t swallow tablets
have had surgery to remove part of your stomach, small bowel or large bowel or you have problems with your digestive system , that may interfere with how you absorb the study drug
take warfarin or a similar drug
take medication that affects body substances called CYP enzymes
have diabetes that isn’t well controlled with medication
have severe liver damage
have HIV
have hepatitis B or hepatitis C
have problems with your heart, such as a heart attack in the last 6 months, high blood pressure that is not well controlled, angina that is not well controlled, an abnormal rhythm of your heart, congestive heart failure or decreased blood flow to the arteries in the heart
have any other serious medical condition or mental health problem that the study team think could affect you while taking part in the study

Other

You:

are sensitive to lenalidomide, thalidomide or rituximab
are pregnant or breastfeeding

Trial design

This is a phase 1/2 study. The study is in 2 parts. In part 1 the researchers looked at the best dose of lenalidomide to give alongside standard doses of ibrutinib and rituximab. They have found this dose and this part of the study is now closed.

Part 2 is open. In part 2, everyone has:

rituximab
lenalidomide
ibrutinib

The study team needs about 83 people to join this part of the study.

You have treatment in cycles. Each 28 day period is 1 cycle of treatment.

You have rituximab as a drip into a vein, once every 4 weeks. It takes between 3 and 6 hours each time. You have up to 6 cycles of rituximab treatment.

Ibrutinib is a capsule. You take them once a day, every day.

Lenalidomide is a capsule. You take them once a day for 21 days followed by 7 days when you don’t take any lenalidomide.

You take your capsules at home. The study team will give you a fresh supply at the beginning of each treatment cycle.

You continue taking ibrutinib and lenalidomide for as long as the study doctor and staff feel it is in your best interest to continue the study. The study doctor will check how the treatment is working and the side effects you may have to help make this decision.

Samples for research

You give some extra blood samples during treatment. You give the samples at specific times and the study team will give you more information about this. They plan to use the samples to:

see how well the treatment is working
find what happens to the drugs in the body
look at genes to help understand more about DLBCL
look for biomarkers to predict who will benefit from treatment

The doctors will ask permission to collect and store some of your blood and a sample of the lymphoma (tissue sample). This is for future research. Researchers will use them to understand more about this treatment and how it works.

You do not have to agree to give these samples if you don’t want to. You can still take part in the study.

Hospital visits

You see a doctor and have some tests before you start treatment. The tests include:

blood tests
urine tests
physical examination
heart trace (ECG )
bone marrow test
CT scan or PET scan

You have rituximab in the outpatient department. You shouldn’t need to stay overnight.

You go to the hospital:

once a week for the first month
twice a month for the next 2 months
once a month after that

At each visit, you see the study doctor for a check up and blood tests. You have a CT or PET scan every 3 months.

You stop treatment if the lymphoma gets worse. You see the study doctor for a check up a month later. Your doctor will discuss other treatment options with you. The study nurse will contact you at home every 3 months to see how you are getting on.

You see the study doctor and have a CT scan every 3 months if you stopped treatment but the lymphoma hasn’t got worse. You then continue to have check ups until either the lymphoma gets worse or you start another anti- cancer treatment.

Side effects

Having lenalidomide, ibrutinib and rituximab together is a new treatment combination. So there might be side effects we don’t know about yet. The study team will monitor you during the time you have treatment and you’ll have a number to call if you are worried about anything.

The most common side effects of ibrutinib include:

diarrhoea or constipation
a drop in blood cells causing an increased risk of infection, bleeding problems
feeling sick or being sick
skin rash and skin infections
fever
high blood pressure
headache
bruising
mouth sores
joint aches and muscle spasms
colds
sinus infection
chest infections (pneumonia)
swelling of the hands or feet

The most common side effects of lenalidomide include:

a drop in the number of blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
blurred vision and cataracts
diarrhoea or constipation
tummy (abdominal) pain
feeling or being sick
weakness
tiredness (fatigue)
swelling
fever or chills
chest infections (pneumonia) or other infections
sore throat
blocked nose or nose bleeds
cough
loss of appetite, indigestion or taste changes
weight loss
problems sleeping
low levels of certain electrolytes in the blood such as calcium
muscle or joint pain
dizziness
itchy, dry skin
changes in blood tests that show how the liver is working
headache
changes in sense of touch or pain, numbness and tingling in your hands and feet (peripheral neuropathy)
shaking (tremor)
feeling sad (depression)
blood clot in the legs, lungs and other organs
high blood sugar

The most common side effects of rituximab include:

infections
joint and muscle pain
tummy pain
tiredness (fatigue)
a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
runny nose (rhinitis)
feeling or being sick
low blood pressure
diarrhoea

There is a small chance you might have an allergic reaction to the drug during the infusion, causing flu like symptoms such as a fever, chills and shivering (rigors). You might also have a headache and feel sick. Your nurse will give you medicines beforehand to try to prevent a reaction. They will keep a close eye on you and treat any problems straight away.