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 Open a glossary item)
  • lenalidomide (helps the immune system Open a glossary item 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 Open a glossary item, basal cell Open a glossary item or squamous cell Open a glossary item 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 Open a glossary item, 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 Open a glossary item to help understand more about DLBCL
  • look for biomarkers Open a glossary item 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:
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:
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.

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Ardeshna

Supported by

Pharmacyclics LLC

Questions about cancer? Contact our information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:

13810

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Around 1 in 5 people take part in clinical trials

3 phases of trials

Around 1 in 5 people diagnosed with cancer in the UK take part in a clinical trial.

Last reviewed:

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