A trial looking at new treatments for follicular lymphoma (REFRACT)
Cancer type:
Status:
Phase:
This trial is comparing new combinations of treatment with
Cancer Research UK supports this trial.
More about this trial
Follicular lymphoma is a type of non-Hodgkin lymphoma (NHL). It is slow growing (low grade) and treatment can keep it under control for a number of years. Sometimes initial treatment stops working or doesn’t work well. You then have chemotherapy, certain
- rituximab and bendamustine
- R-CVP
- R-CHOP
- rituximab and lenalidomide
- obinutuzumab and bendamustine
Doctors are looking at ways to improve treatment for people whose lymphoma has come back or treatment isn’t working.
In this trial they are looking at newer targeted cancer drugs. There are 3 treatment parts in this trial. Part 1 is looking at epcoritamab and lenalidomide.
Epcoritamab is a type of drug called a bispecific T-cell engager (BiTE). You pronounce epcoritamab as ep-cor-ee-tah-mab.
BiTEs have 2 parts. One part attaches to a type of immune system cells called
Lenalidomide is a targeted cancer drug. It is already used as a treatment for people whose follicular lymphoma has come back or treatment has stopped working. Doctors think that adding epcoritamab to lenalidomide can improve how well it works.
Part 2 and part 3 of this trial aren’t open yet. We plan to add information to the summary about these parts when they open.
In this trial, some people have the new treatments and some people have standard treatment. Doctors aren’t sure how well the new treatments will work so they are doing this trial to find out more.
The main aims of the trial are to find out:
- how well the new combinations of treatment work compared to standard treatment
- more about the side effects
- how treatment affects
quality of life
Who can enter
The following bullet points are a summary of 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.
Who can take part
You may be able to join this trial if all of the following apply. You:
- have follicular lymphoma that has come back (relapsed) or continued to grow despite treatment (refractory) and your doctor thinks
systemic treatment could help - have follicular lymphoma that is low grade or slow growing and this was confirmed when you had a tissue sample (
biopsy ) taken in the last 6 months. Your doctor will know this. - have the protein CD20 on the surface of lymphoma cells (CD20 positive). Your doctor will know this.
- are suitable to have standard treatment
- have had at least one
course of treatment in the past that included a combination ofimmunotherapy and chemotherapy. You can take part if you have already had radiotherapy or rituximab on its own. - have lymphoma that the doctor can assess on a scan
- are up and about for at least half the day but might not be able to work (performance status 0,1 or 2)
- have satisfactory blood test results
- are willing to use reliable contraception during the trial and for a period after if there is any chance you or your partner could become pregnant
- give
informed consent - are at least 18 years old
Who can’t take part
Cancer related
You cannot join this trial if any of these apply. You:
- have
high grade or faster growing lymphoma or you had this in the past. Your doctor will know this. - have lymphoma in the brain or spinal cord or you have had this in the past
- have had a
stem cell transplant with someone else’s cells - have had lenalidomide within 12 months of starting trial treatment
- have had epcoritamab or a similar drug in the past
- have had CAR T-cell treatment within 100 days of starting trial treatment
- are going to have a stem cell transplant or
maintenance treatment within 6 months of starting trial treatment - have had immunotherapy in combination with chemotherapy that included a
platinum drug - have had cancer treatment in the last 4 weeks such as immunotherapy, chemotherapy or a targeted cancer drug. Or you have had
steroid treatment in the last 7 days unless it was a low dose. - have had another cancer within 2 years of joining the trial. You can take part if you had
early cancer of the cervix,non melanoma skin cancer , early bladder cancer or prostate cancer or another cancer that has been successfully treated and there have been no signs of it for 2 years.
Medical conditions
You cannot join this trial if any of these apply. You:
- have had a heart attack in the last 6 months or you have a significant
heart problem that needs treatment - have had major surgery within 30 days of starting trial treatment
- have HIV, hepatitis C that isn’t well controlled with medication, an active hepatitis B infection or another active infection that needs treatment
- are having or have had recent steroid treatment to damp down the
immune system unless it is a low dose - have had an
organ transplant - have another medical condition or mental health condition that could affect you taking part
Other
You cannot join this trial if any of these apply. You:
- are allergic to rituximab or similar drugs
- are allergic to any of the drugs in the trial. You might be able to join if you are allergic to a particular standard treatment and not allergic to other potential standard treatment.
- are pregnant or breastfeeding
Trial design
This is a phase 2 trial. The team need 284 people in the UK to take part.
There are 3 treatment parts in this trial. The team need:
- 126 people to join part 1
- 79 people to join part 2
- 79 people to join part 3
Each treatment part is randomised. A computer puts you into a treatment group. Neither you nor your doctor will be able to decide which group you are in.
At the moment, only part 1 is open.
In treatment part 1, you have one of the following:
- standard treatment
- epcoritamab and lenalidomide
Standard treatment group
In this group you have one of the following standard combinations of treatment:
- rituximab and bendamustine
- R-CVP
- R-CHOP
- rituximab and lenalidomide
- obinutuzumab and bendamustine
The treatment you have depends on which one your doctor thinks will work best for you. They will talk to you about this.
You have obinutuzumab and rituximab as a drip into a vein.
Lenalidomide is a capsule you take by mouth.
The other standard treatments are chemotherapy drugs. How you have chemotherapy depends on the group you join. You have some chemotherapy drugs as a drip into a vein. You might need a
You may have some chemotherapy drugs as a tablet you take by mouth.
The team tell you when you have treatment and for how long.
Epcoritamab and lenalidomide group
You have treatment in cycles. Each 4 week period is a
You have epcoritamab as an injection under the skin. In the first 3 cycles of treatment you have injections once a week. After that you have them once a month.
Lenalidomide is a capsule. You take them once a day, every day for 3 weeks. You then don’t take the capsules for a week.
You have lenalidomide and epcoritamab for up to a year as long as treatment is working and the side effects aren’t too bad.
Both groups
You stop treatment if your lymphoma gets worse. Your doctor will talk to you about other treatment options.
Samples for research
The researchers might ask to take an extra tissue sample (
They plan to use the samples to:
- see how well the treatment is working
- look for substances called
biomarkers to help work out why treatment might work for some people and not for others - look at the make up of cancer cells to see if it is possible to target treatment to individuals
You can say no to having the extra tissue sample taken. It won’t affect you taking part in the rest of the trial.
The team will ask to collect a sample of tissue if you have any routine bone marrow tests during treatment. You don’t have extra bone marrow tests as part of the trial.
The team also ask you to provide a spit (saliva) sample before you start treatment.
If there are any remaining samples the team will ask to store this away for future research. You do not have to agree to your samples being stored. You can still take part in the trial.
Quality of life
The trial team ask you to fill out some questionnaires:
- before you start treatment
- at set times during and after treatment
The questionnaires ask about side effects and how you’ve been feeling. This is called a quality of life study.
Hospital visits
You see the doctor and have tests before you can take part. These include:
- blood tests
- urine tests
- a
physical examination - heart trace (ECG)
- PET-CT scan
You might also need to have a bone marrow test.
You also have a test of your nervous system called a neurological examination. This is only if you have epcoritamab and lenalidomide. This is to check your brain function and if there are any changes during treatment. You perform simple tasks such as naming objects and writing a sentence. This takes about 5 minutes to complete. You repeat this examination regularly during treatment.
During treatment you see the doctor regularly. This is for blood tests and to see how you are.
Trial scans
You have a PET-CT scan at:
- 3 months (this is optional)
- 6 months
Follow up
You see the trial team 2 months after you stop treatment. After that they follow you up every 6 months. You might see them at a routine hospital appointment or they may call you to see how you are getting on.
Side effects
The trial team monitor you during treatment and afterwards. Contact your advice line or tell your doctor or nurse if any side effects are bad or not getting better.
Your doctor will tell you about all the possible side effects of treatment. You’ll have a chance to ask any questions you may have.
Epcoritamab and lenalidomide is a new combination of treatment. So we don’t know what all the side effects of this combination are.
The most common side effects of epcoritamab include:
- the release of chemicals called cytokines. The side effects of the release of cytokines can be mild or severe. It can cause high temperatures, chills, tiredness, feeling or being sick, diarrhoea and headaches.
- a fast heartbeat
- headache and dizziness
- low levels of oxygen in the blood and shortness of breath
- a skin reaction where you have the injection. You might have swelling, pain, a rash, bleeding or redness.
- feeling or being sick
- tummy (abdominal) pain
- diarrhoea or constipation
- a drop in blood cells causing an increased risk of infection, bruising and bleeding, breathlessness and tiredness
- urine infections or infections of the sinuses, throat, airways or lungs
- joint stiffness and back pain
- cough
- pneumonia
- changes to how your liver works
- skin rash
- a problem with how your
adrenal glands work - a high temperature and a low number of
neutrophils - high temperatures (fever)
- loss of appetite
- difficulty sleeping
We have information about the following treatments and their side effects:
Location
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.
Chief Investigator
Dr Mark Bishton
Dr Kim Linton
Supported by
Cancer Research UK
Genmab
National Institute for Health Research (NIHR)
University of Birmingham
Other information
This is Cancer Research UK trial number CRUK/22/009.
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040