Purpose of trial
The aim of this trial is to find out if adding acalabrutinib to standard treatment can improve the response and outcome of participants with chronic lymphocytic leukaemia (CLL) that has changed (transformed) to a faster-growing type of lymphoma. This is called Richter syndrome.
There are two parts to this trial: a randomised trial (the main element of the trial) and two additional treatment groups (known as ‘cohorts’).
The randomised part of the trial
People with newly-diagnosed Richter syndrome who have not had CHOP chemotherapy and have not had ibrutinib in the last 4 weeks can be considered for the randomised part of the trial. People in this part of the trial are randomly allocated to one of two treatment groups:
You can’t choose which treatment you have and neither can your doctor. If you are suitable for the randomised part of the trial and you want to participate, you will be allocated a treatment group when you are registered on the trial. You will be told which treatment you are having and given information about it.
- People who took part in the randomised part of the trial and had R-CHOP on its own might be given the opportunity to enter Cohort 1 if their disease comes back (relapses) or does not respond (refractory). People in Cohort 1 are treated with acalabrutinib on its own.
- People with newly-diagnosed Richter syndrome who have not had CHOP chemotherapy but who have been treated with ibrutinib in the last 4 weeks can be considered for Cohort 2. People in Cohort 2 do not take part in the randomised part of the trial. People in Cohort 2 are treated with R-CHOP plus acalabrutinib.
R-CHOP is given in cycles. Each cycle is 3 weeks. You have six cycles.
- Rituximab is an antibody therapy. You have it through a drip into a vein on day 1 of each cycle.
- CHOP is a combination of four chemotherapy drugs. These are called cyclophosphamide, vincristine, doxorubicin and prednisolone. You have cyclophosphamide, vincristine and doxorubicin through a drip into a vein on day 1 of each cycle. You have prednisolone as oral tablets once a day for the first 5 days of each cycle.
Acalabrutinib is a type of targeted drug called a cell signal blocker. It blocks a protein called ‘BTK’ on B cells. BTK is a part of a pathway that helps B cells to stay alive and divide. Blocking BTK can make B cells die or prevent them dividing.
Acalabrutinib is a capsule that you take by mouth twice a day.
- If you are having acalabrutinib in combination with R-CHOP, you have it twice a day on days 6 to 21 of each cycle for six cycles. After that you take it twice a day every day. You carry on taking it unless your lymphoma gets worse or you experience troublesome side effects.
- If you are having acalabrutinib on its own, you have it twice a day every day. You carry on taking it unless your lymphoma gets worse or you experience troublesome side effects.
Who can enter
Your consultant can give you advice on whether you might be suitable for this trial.
Around 105 people are needed for this trial.
You may be able to enter if:
- You have Richter syndrome (chronic lymphocytic leukaemia that has transformed to a faster-growing type of lymphoma), and you have not had previous treatment for it.
- You are well enough to take part in the trial.
- Your blood and other health test results are satisfactory.
- You and your partner are willing to use reliable contraception if there is any chance of you or your partner becoming pregnant.
- You are 18 or over.
You won’t be able to enter if:
- You have been treated with acalabrutinib before.
- You still have significant side effects from your previous treatment.
- You have any health problems that your doctor thinks might make it unsafe for you to have the trial treatment.
- Your lymphoma is in your central nervous system (CNS; brain and spinal cord).
- You have any conditions that might make it difficult for you to follow the instructions involved in the trial.
- You’ve had surgery in the last 4 weeks.
- You’ve had any experimental treatment in the last 4 weeks.
- You’re having treatment as part of another clinical trial.
- You are taking warfarin or another anticoagulation (anti-clotting) drug.
- You have HIV or hepatitis B.
- You have an active infection that needs treatment.
- You have serious heart disease.
- You have a bleeding disorder.
- You have another cancer that needs treatment, except certain localised cancers.
- You have an illness that makes it difficult for you to absorb food.
- You’ve had a stroke or bleeding on your brain in the last 6 months.
- You are pregnant or breastfeeding.
- You’ve had a bad reaction to any of the study treatments in the past.
More information about this trial is available at clinicaltrials.gov/ct2/show/NCT03899337