A trial of R-CHOP and acalabrutinib for people with Richter’s syndrome (STELLAR)
Cancer type:
Status:
Phase:
This trial is looking at acalabrutinib to see if it can improve treatment for people with Richter’s syndrome.
Chronic lymphocytic leukaemia (CLL) can sometimes develop into a condition called Richter’s syndrome. Richter's syndrome is a type of non-Hodgkin lymphoma (NHL).
More about this trial
The usual treatment for Richter’s syndrome is R-CHOP. This is a combination of chemotherapy drugs and a targeted drug called rituximab. This treatment can help but sometimes the lymphoma comes back. So researchers are looking for ways to improve treatment.
In this trial, they are looking at adding a drug called acalabrutinib to R-CHOP. This combination is called RA-CHOP.
Acalabrutinib is a type of targeted cancer drug called a cancer growth blocker. It stops the signals that cancer cells use to divide and grow. We know from early research that it might work for people with Richter’s syndrome.
There are 2 open parts to this trial. Which part you join depends on a few factors such as the treatment you have had in the past. So you have 1 of the following:
- R-CHOP or R-CHOP and acalabrutinib
- acalabrutinib on its own
The main aims of the trial are to:
- compare R-CHOP with RA-CHOP
- see if acalabrutinib improves treatment
- learn more about the side effects
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.
There are 2 open groups in this trial:
- the
randomised part 
- group 1 (or cohort 1)
Who can take part
You may be able to join the randomised part of the trial if all of the following apply. You:
- are suitable to have R-CHOP
- haven’t had R-CHOP in the past
- have chronic lymphocytic leukaemia (CLL) and newly diagnosed Richter’s syndrome
- haven’t had a drug called ibrutinib in the last 4 weeks
To join cohort 1 you joined the randomised part of the trial and had R-CHOP. Or you have previously had R-CHOP and the lymphoma got worse or came back afterwards.
As well as the above, for all parts of the trial the following must also apply.
You:
- are well enough to be up and about for at least some of each day, even if you need help looking after yourself (performance status 0, 1, 2 or 3)
- are willing to use reliable contraception during the trial and for 12 months afterwards if there is any chance you or your partner could become pregnant
- are at least 18 years old
Who can’t take part
You cannot join this trial if any of these apply.
Cancer related
You:
- have had acalabrutinib in the past
- have CLL or a type of NHL called diffuse large B cell lymphoma (DBCL) in the brain or spinal cord
- have any other cancer that needs treatment apart from
basal cell skin cancer , carcinoma insitu (CIS ) of the cervix or squamous cell skin cancer - have had an experimental treatment as part of a clinical trial in the last 4 weeks or you are taking part in a trial
Medical conditions
You:
- have a problem with how your blood clots
- are having treatment to thin your blood such as warfarin
- have had major surgery within 30 days of being put into a treatment group
- have a problem with your gut that affects how you absorb medication
- have a problem with your heart such as angina, congestive heart failure or an abnormal heart beat that isn’t well controlled with medication
- have had a stroke in the last 6 months or a bleed into the brain
- have a long term infection that isn’t getting better with treatment or any active infection such as TB or a hepatitis B infection
- have HIV
- have any other medical condition or mental health problem that means the trial team think you won’t be able to take part
Other
You:
- are allergic to any of the drugs in the trial
- have a problem with drugs or alcohol
- are pregnant or breastfeeding
Trial design
This is a phase 2 trial. It is taking place in the UK.
There are 3 treatment groups in this trial. Your doctor will tell you which treatment group you go into. You have 1 of the following:
- R- CHOP or R-CHOP and acalabrutinib (randomised part of trial)
- acalabrutinib only (cohort 1)
- R-CHOP and acalabrutinib (cohort 2). Please note, this group is now closed to recruitment.
R-CHOP or R-CHOP acalabrutinib
This part of the trial is randomised. You are put into 1 of 2 groups by a computer. Neither you nor your doctor can decide which group you are in. You have 1 of the following:
- R-CHOP (standard treatment)
- R-CHOP and acalabrutinib (RA-CHOP)
The trial team need 60 people to join this part of the trial.
Everyone taking part has R-CHOP. You have
. Each 3 week period is a cycle of treatment. The first day of treatment is called day 1. You:
- have the chemotherapy drugs as a drip into a vein on day 1
- take prednisolone tablets on day 1 to day 5
- take acalabrutinib capsules, twice a day on days 6 to day 21
Everyone has up to 6 cycles of treatment. This takes about 4 months. Those in the acalabrutinib group might be able to continue to take it for longer if treatment is working.
You stop treatment if it isn’t working. Your doctor will discuss further treatment with you.
Acalabrutinib on its own (Cohort 1)
This part is for people who had R-CHOP in the past, but their Richter’s Syndrome didn’t improve, got worse or came back.
The trial team need 30 people to join this part of the trial.
You have acalabrutinib. It is a capsule. You take them twice a day, everyday. The trial team tell you how many capsules to take.
You have treatment as long as it is working and the side effects aren’t too bad.
R-CHOP and acalabrutinib (Cohort 2)
This group is now closed to recruitment.
Samples for research
The researchers ask for samples () from bone marrow tests that you have done as part of your standard care. They also ask to take some extra blood samples. Where possible, you have these at the same time as your routine blood tests.
They also ask you to give a sample of tissue from a lymph node. They ask for a sample before you start treatment and if your cancer gets worse.
They plan to use the samples to work out why treatments work for some people and not others. And to learn more about Richter’s syndrome.
Quality of life
You fill out a questionnaire before starting treatment, at set times during the trial and after finishing treatment. The questionnaire asks about any side effects you have had and about how you have been feeling. This is called a quality of life study.
Hospital visits
You see a doctor and have some tests before you can join the trial. These include:
- physical examination
- blood tests
- bone marrow test
- PET-CT scan
- heart trace (
ECG )
The trial team might also ask you to give a .
You have a:
- CT scan after 4 cycles of treatment
- PET-CT scan after 6 cycles of treatment or if the CLL gets worse
You have regular check ups when you are on trial treatment. The trial team follow you up every 3 months when you finish treatment 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.
The most common side effects of acalabrutinib include:
- headaches
- an increased risk of infection
- an increased risk of bruising and bleeding such as nose bleeds
- an increased risk of tiredness and breathlessness (
anaemia ) - diarrhoea or constipation
- feeling or being sick
- skin rash
- muscle, joint or tummy (abdominal) pain
- tiredness (fatigue) or a lack of energy
- dizziness
- developing a
second cancer - an abnormal heart rhythm called atrial fibrillation
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
- symptoms of an allergic reaction that include high temperature (fever), chills, feeling or being sick and difficulty breathing
- 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)
- bladder problems such as pain passing urine or discoloured urine
- high levels of sugar in the blood
- skin and nail changes
- liver problems
- eye problems
- jaw pain
- swelling and pain in the joints
Because they can interfere with the way the drugs work the trial team ask you to avoid:
- grapefruit, grapefruit juice, Seville orange juice
- herbal remedies or dietary supplements (especially St John’s Wort)
- medications to reduce the amount of acid your stomach makes if you are having acalabrutinib. These include drugs such esomeprazole (Nexium) and omeprazole.
We have more 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
Dr Toby Eyre
Supported by
Blood Cancer UK
Trials Acceleration Program (TAP)
Acerta Pharma
University of Birmingham
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
