A trial of acalabrutinib with R-CHOP for people with diffuse large B cell lymphoma (ACCEPT)
Please note - this trial is no longer recruiting patients. We hope to add results when they are available.
Cancer type:
Status:
Phase:
This trial is looking at whether acalabrutinib can improve treatment for people with a type of non Hodgkin lymphoma called diffuse large B cell (DLBCL).
Cancer Research UK supports this trial.
More about this trial
You usually have treatment called R-CHOP if you have diffuse large B cell lymphoma. R-CHOP is a combination of chemotherapy drugs and a targeted cancer drug (a biological therapy).
This treatment works well for most people but for some the chemotherapy may stop working or the lymphoma comes back after a short period. So doctors want to improve treatment. In this trial they are looking at a new drug called acalabrutinib.
Acalabrutinib is a type of targeted cancer drug called a Bruton tyrosine kinase (BTK) inhibitor. It blocks a protein in the lymphoma cells which plays a role in stopping the cells from dying. Doctors hope that adding acalabrutinib to R-CHOP will improve the way it works.
The trial is in two parts (or phases). In phase 1 the aims are to understand more about:
- how safe acalabrutinib is
- how it is processed by the body
- the safest dose that can be given with R-CHOP
The trial will only move into phase 2 if phase 1 is successful. The aims of phase 2 are to:
- see how acalabrutinib given with R-CHOP works as treatment for lymphoma
- learn more about the side effects of acalabrutinib
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 been diagnosed with diffuse large B cell lymphoma (DLBCL) which expresses CD20 (the trial team will check for this)
- You have stage 1 to stage 4 DLBCL
- You have a sample of your lymphoma available from when you were diagnosed for testing
- You have an area of lymphoma that can be measured using a scan and which is at least 15 mm
- You have not had any treatment for your lymphoma and you are well enough to have R-CHOP with the aim of curing your DLBCL
- You are well enough to be up and about for at least half the day (performance status 0, 1 or 2) – you might be able to take part if your performance status is 3 as long the reason for this is your DLBCL
- You have satisfactory blood test results
- Your heart is working well enough (this will be tested before you have any treatment)
- You are able to swallow capsules
- You are willing to use reliable contraception during the trial and for 12 months afterwards if there is any chance that you or your partner could become pregnant
- You are aged between 16 and 64 years old
You cannot join this trial if any of these apply.
Cancer related
- You have a type of lymphoma called primary mediastinal lymphoma or primary central nervous system (CNS) lymphoma
- You have had a type of lymphoma called indolent lymphoma (or low grade lymphoma), this includes follicular lymphoma, mantle cell lymphoma, lymphoplasmacytic lymphoma and skin lymphomas
- You have had treatment with a type of biological therapy called a BCR inhibitor or BCL-2 inhibitor such as ibrutinib, idelalisib or venetoclax
- You have had any other cancer in the last 2 years, unless it was a very early stage and has been successfully treated (the trial team can advise you about this)
- You are taking part in any other clinical trial to treat your DLBCL
Medical conditions
- You have had major surgery within 4 weeks of starting treatment in this trial and you must have recovered from any prior surgery
- You have had treatment with a type of drug called an immunotherapy for any reason within 4 weeks of starting treatment in this trial
- You have had a stroke or a bleed in your brain in the last 6 months
- You have a condition which means you are at risk of bleeding such as haemophilia
- You have a condition that affects your ability to digest drugs and nutrients for example one of the following- malabsorption syndrome, all or part of your stomach or small bowel removed, a gastric bypass, inflammatory bowel disease that is causing symptoms, a blockage in your bowel (a bowel obstruction)
- You have had a heart attack in the past 6 months or any other major heart problem such as congestive heart failure or an abnormal heartbeat (arrhythmia) which is not well controlled
- You have an infection that affects your whole body (systemic infection) that is not controlled by treatment
- You have had treatment to thin your blood such as warfarin within 7 days of starting treatment with acalabrutinib. You may be able to take part if the treatment is either low dose aspirin or low molecular weight heparin
- You take drugs called proton pump inhibitors such as omeprazole or lansoprazole. You might be able to take part if you are able to switch to short acting H2 receptor antagonists such as cimetidine or ranitidine or to an antacid
- You need to take any drugs that have a strong effect on body substances called cytochrome P (CYP) enzymes
- You are HIV positive
- You have hepatitis B or hepatitis C
- You have any other serious medical condition or mental health problem that the trial team think could affect you taking part
Other
- You have had a live vaccine within 4 weeks of starting treatment in the trial
- You are pregnant or breastfeeding
Trial design
This is a phase 1/2 trial. Phase 2 will only start if phase 1 is successful. The doctors need about 40 people to take part in both phase 1 and 2.
In phase 1 the doctors want to find the safest dose of acalabrutinib that can be given with R-CHOP. They want to test 2 doses. There will be 6 to 12 people in each group. The first group have a fairly low dose of acalabrutinib. The next group have a higher dose. The dose you have will depend on when you join the trial.
When the doctors have found the best dose they want to test this with a group of 15 people. This is phase 2 of the trial. In this part of the trial, doctors want to learn more about how well acalabrutinib works and about the side effects.
Everyone taking part has R-CHOP. This is the standard treatment for DLBCL. The first day of treatment is called day 1. You have all the chemotherapy drugs and the targeted cancer drug (rituximab) on this day. You then have a break for 20 days. This is a treatment cycle. Each cycle is 21 days and you have up to 6 cycles of treatment. You have R-CHOP as a drip in the vein or as an injection.
Acalabrutinib is a capsule. You take the first dose on day 1 of your second cycle of R-CHOP and then every day for 21 days.
After six cycles of R-CHOP and acalabrutinib you have two further cycles of acalabrutinib alone. Each cycle is 28 days.
Samples for research
You give some extra blood samples during the time you have treatment. The blood samples need to be taken at specific times and the trial team will provide you with more information about this. The samples are tested to measure the amount of acalabrutinib in your blood. You may hear these tests called pharmacokinetics.
The doctors will ask permission to collect and store some of your blood and tissue for future research. These samples will be used to understand more about how acalabrutinib works in your body and what affect it has on the lymphoma.
You will also be asked if you are willing to have a sample of tissue taken (a biopsy). This would be done during your second cycle of treatment.
You do not have to agree to have your blood and tissue stored or to have the biopsy. You can still take part in the trial.
Hospital visits
You see the doctor and have some tests before starting the trial. The tests include:
- a physical examination
- blood tests
- heart trace (ECG)
- heart scan (echocardiogram) or MUGA scan
- bone marrow test
- CT scan and PET scan or a PET-CT scan
You go to hospital to have your treatment. You should not need to stay overnight.
During your treatment you see the doctors and have blood tests. You also have 3 more ECGs and a heart scan. You have a CT scan or PET-CT scan so the doctors can check your lymphoma. The trial team will tell you when you have these scans.
You see the doctors about 4 weeks after your last dose of chemotherapy. You have another CT and PET scan or PET-CT scan and you might also have another bone marrow biopsy if necessary.
When you finish R-CHOP you carry on taking acalabrutinib for 56 days. After this you will continue to be followed up by the trial team for two years.
Side effects
As acalabrutinib is a new drug, there may be side effects we don’t know about yet.
The trial team will monitor you during the time you have treatment and you’ll have a phone number to call them if you are worried about anything.
The possible side effects of acalabrutinib are:
- a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
- sensitivity to sunlight (phototoxicity) - the risk of this is low
The most common side effects of R-CHOP are:
- a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
- hair loss
- feeling or being sick
- sore mouth
- loss of appetite and taste changes
- diarrhoea or constipation
- numbness and tingling in your hands and feet (peripheral neuropathy)
- tiredness (fatigue)
We have more information about R-CHOP.
Because they can interfere with the way the drugs work the trial team will ask you to avoid:
- grapefruit, grapefruit juice, Seville orange juice
- herbal remedies or dietary supplements (especially St John’s Wort)
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
University Hospital Southampton NHS Foundation Trust
Haematological Malignancies Diagnostic Service (HMDS)
Cancer Research UK
Experimental Cancer Medicine Centre (ECMC)
Other information
This is Cancer Research UK trial number CRUKDE/16/006
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
