A trial looking at acalabrutinib for Diffuse Large B Cell Lymphoma (REMoDL)
Cancer type:
Status:
Phase:
This trial is looking at giving acalabrutinib with chemotherapy for Diffuse Large B Cell Lymphoma (DLBCL).
This trial is for people with DLBCL that haven’t had treatment and are well enough to have chemotherapy with the aim to cure their cancer.
Cancer Research UK supports this trial.
More about this trial
R-CHOP is a combination of a 
and chemotherapy. It is a for DLBCL.
R-CHOP is a successful treatment for most people with DLBCL. But for some it doesn’t work or their lymphoma comes back after treatment. Researchers think that adding acalabrutinib to R-CHOP might help these people.
Doctors already use acalabrutinib to treat other blood cancers called chronic lymphocytic leukaemia and mantle cell lymphoma.
Acalabrutinib is a called a cancer growth blocker. It works by blocking an enzyme that lymphoma cells need to grow and divide.
A previous trial called ACCEPT found that it is safe to have acalabrutinib with R-CHOP.
The aims of this trial are to find out:
- how well acalabrutinib with R-CHOP works
- more about the side effects
- how it 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 diffuse large B cell lymphoma (DLBCL) that has the protein CD20 on the lymphoma cells
- have an area of lymphoma that measures 1.5cm or more across
- are fit enough to have chemotherapy and immunotherapy (R-CHOP) with the aim to cure
- can look after yourself but might not be able to work (performance status 0, 1 or 2). You might be able to join if you need help looking after yourself because of your lymphoma. Your doctor can tell you about this.
- have satisfactory blood test results
- are willing to have a heart scan to find out whether your heart works well enough. Your doctor will arrange for you to have this scan.
- are willing to use at least 1 very reliable contraception during treatment and for a time after if there is any chance you or your partner could become pregnant
- are at least 16 years old
Who can’t take part
Cancer related
You cannot join this trial if any of these apply. You have:
- already had treatment for lymphoma
- had a previous low grade (indolent) lymphoma
- lymphoma in the middle of the chest
- lymphoma in the brain or spinal cord
- have another cancer. This is apart from successfully treated
non melanoma skin cancer , in situ carcinoma of the cervix or any cancer that is treated and there has not be a sign of it for at least the past 2 years.
Medical conditions
You cannot join this trial if any of these apply. You:
- have had a stroke or a bleed in the brain within the past 6 months
- have a bleeding problem or disease such as haemophilia
- are taking or need to take warfarin or similar drug within 7 days of starting the trial treatment. You can join if you are having low weight molecular heparin or taking a low dose of aspirin.
- have already had treatment with a drug that works in the same way as acalabrutinib. Your doctor will know this.
- are taking medication that strongly affects the CYP enzymes
- are taking indigestion or heartburn medication called proton pump inhibitors such as omeprazole and lansoprazole. You might be able to join the trial if your doctor can change these medications for another type.
- have a blood disorder called autoimmune haemolytic anaemia (AIHA) or idiopathic thrombocytopenic purpura (ITP) that isn’t controlled
- have major surgery within 4 weeks of starting trial treatment or you have not recovered from any previous surgery
- are taking a dose of steroids that is 30mg or more a day unless it is for your lymphoma
- have had
heart problems in the past 6 months - have hepatitis B, hepatitis C, HIV or another active infection
- have difficulty with or are unable to swallow tablets or capsules
- have a problem with your
digestive system that affects how well your body absorbs medication taken by mouth - have an
immunotherapy within 4 weeks of starting trial treatment - have inflammation of the lungs
- are taking part in another clinical trial
- have any other medical condition or mental health problem that could affect you taking part
Other
You cannot join this trial if any of these apply. You:
- have a
live vaccine within 4 weeks of starting trial treatment. The COVID-19 vaccines aren’t live vaccines. - are allergic to any of the drugs or any of their ingredients
- are pregnant or breastfeeding
Trial design
This is a phase 2 trial. The team need up to 375 people to join.
Everyone has 1 with R-CHOP.
While you are having this cycle of R-CHOP your doctor will work out the risk of the lymphoma coming back. This is called the International Prognostic Index. This gives a score from 0 to 5. A score of 0 or 1 means there is a low risk of the lymphoma coming back. A score of 2 to 5 means there is a medium (intermediate) to high risk of the lymphoma coming back.
If you have a score of 0 or 1, a computer puts you into 1 of 2 treatment groups. Neither you nor your doctor can choose which group you are in. This is . Every 2 out of 3 people will go into the R-CHOP and acalabrutinib group.
If you have a score of 2 to 5 you go into the R-CHOP and acalabrutinib group.
The groups are:
- R-CHOP
- R-CHOP and acalabrutinib
R-CHOP is;
- rituximab
- cyclophosphamide
- doxorubicin
- vincristine
- prednisolone
You start all the drugs on the same day. You have rituximab, cyclophosphamide, vincristine and doxorubicin as a drip into a vein. Prednisolone is a tablet. You take it for 5 days. You have treatment every 3 weeks. Each 3 week period is a cycle of treatment.
People in the group taking acalabrutinib start taking it when you have your 2nd cycle of treatment. Acalabrutinib is a tablet or a capsule. You take it twice a day every day.
You can have a total of 6 cycles of treatment as long as it is helping and the side effects aren’t too bad.
Quality of life
You fill in a questionnaire:
- before starting treatment
- 3 times during treatment
- at the end of treatment then
- 5 times after treatment
The questions ask about:
- your general health
- side effects
- what you can do in your daily life
This is a quality of life questionnaire.
Samples for research
The team ask for a piece of tissue sample from when you were diagnosed. They use these to look for changes () in the of the lymphoma cells. These gene changes might show why some treatments work better than others and why the lymphoma grows.
You also give 3 extra blood samples for the trial. Where possible the team take these when you have your routine bloods. They use these samples to look for small pieces of the and RNA of the lymphoma in the blood (). Researchers want to find out:
- if it is possible to detect these small pieces of DNA and RNA
- whether they might help tell how well treatment is working
Hospital visits
You see the doctor to have tests before taking part. These tests include:
• a
• blood tests
• PET-CT scan or a separate CT scan and PET scan
• heart trace ()
• heart scan ( or )
• pregnancy test (if applicable)
You see the doctor regularly while having treatment. This is to see how you are and for blood tests.
You have a PET-CT scan at 6 weeks (treatment cycle 2).
At the end of treatment you see the doctor and have a PET-CT scan or a CT with a. You then see them and have a CT scan with a contrast medium:
- every 3 months in the first year
- every 4 months for the second year and
- then every year until the last person recruited has completed 2 years of follow up
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.
Acalabrutinib is a new drug and there might be side effects we don’t know about. The side effects reported include:
- headache
- bleeding such as nose bleeds or can be more serious
- bruising
- diarrhoea or constipation
- feeling or being sick
- tummy (abdominal) pain
- skin rash
We have information about R-CHOP.
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
Professor Andrew Davies
Supported by
AstraZeneca
Cancer Research UK
University Hospital Southampton NHS Foundation Trust
National Institute for Health Research (NIHR)
Acerta Pharma BV
Other information
This is Cancer Research UK trial number CRUKE/19/017.
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
