Last year in the UK over 60,000 cancer patients enrolled on clinical trials aimed at improving cancer treatments and making them available to all.
A study of venetoclax and ibrutinib for chronic lymphocytic leukaemia (CLARITY)
This study is for people with chronic lymphocytic leukaemia (CLL) that has come back or treatment has stopped working.
More about this trial
Chemotherapy and biological therapy are the usual treatments for CLL. But doctors are always looking for new treatments.
Ibrutinib is a
Venetoclax is also a biological therapy. It blocks the functions of a protein found in CLL cells. This causes these cells to die. Researchers think this might be a useful treatment for CLL but they want to find out for sure.
The aims of the trial are to
- find out how well ibrutinib and venetoclax work
- find out how safe it is
- learn more about the side effects
Who can enter
The following bullet points list the entry conditions for this study. Talk to your doctor or the study team if you are unsure about any of these. They will be able to advise you.
You may be able to join this study if you have CLL and 1 of the following applies.
- Your CLL didn’t go away completely or a little bit (you didn’t have a complete or partial response) after having a drug such as fludarabine alone or with chemotherapy
- Your CLL came back within 6 months of responding to a drug such as fludarabine alone or with chemotherapy
- Your CLL came back at any time after having fludarabine, cyclophosphamide and rituximab (FCR) or bendamustine and rituximab or a similar type of monoclonal antibody drug
- You have CLL with the part of the 17th chromosome missing (17p) and your CLL got worse after at least 1 treatment
As well as the above, the following must also apply.
- You have symptoms such as an enlarged
spleenor low levels of red blood cellsor plateletsand you need to have treatment
- Your liver and kidneys are working well
- You have satisfactory blood test results
- You are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
- You are willing to use reliable contraception during treatment and for up to 3 months afterwards if there is any chance that you or your partner could become pregnant
- You are at least 18 years old
You cannot join this study if any of these apply.
- Your CLL has changed into another type of leukaemia
- You have leukaemia in your brain or spinal cord
- You have mantle cell lymphoma
- Your CLL tests positive for proteins such as CD19, CD5, CD23, CD43 and CD20
- You have had a
monoclonal antibodydrug in the last 2 months
- You have had previous treatment with ibrutinib, venetoclax or similar drugs
- You have had treatment with an experimental drug in the last 28 days
- You have a problem with your heart that means you are comfortable at rest but your physical activity is limited due to heart palpitations, shortness of breath and chest pain
- You have any problems with the way your blood clots
- You have had a transplant with somebody else’s cells (an
allograft) unless it was more 6 months ago, you have stopped taking drugs to help your immune systemand there is no sign of graft versus host disease
- You have another cancer apart from basal cell skin cancer
- You have a condition called autoimmune haemolysis or a low platelet count (thrombocytopenia) that isn’t well controlled
- You have had blood thinning drugs such as warfarin or vitamin K within a week of starting treatment in the trial
- You have taken any medication that blocks an enzyme called CYP3A4 in the 7 days before joining this trial
- You are sensitive to ibrutinib, venetoclax or anything it contains
- You are known to have HIV
- You have an active hepatitis B or hepatitis C infection
- You can’t have medicine that reduces levels of uric acid in the body
- You have had major surgery in the last month
- You have had a
live vaccinein the last 28 days
- You have had steroids in the last 7 days apart from inhalers, cream or steroids to replace hormones in the body
- You have any other serious medical condition or mental health problem that the study team think could affect you taking part
- You are pregnant or breastfeeding
This phase 2 study is based in the UK. Researchers need 50 people to take part.
Everyone has ibrutinib and venetoclax.
- Ibrutinib is a capsule. You take 3 capsules once a day every day
- Venetoclax is a tablet you take once every day.
To begin with you have ibrutinib for 8 weeks. You then start taking venetoclax. You start with a low dose and your doctor will gradually increase the dose as long as you don’t have bad side effects. The doctor or study nurse will let you know what dose to take each week.
When you start having ibrutinib and venetoclax together, you may still have some leukaemia cells around. When cancer cells die, chemicals in the cells are suddenly released into your blood. This changes the normal balance of chemicals circulating in your body. This is called tumour lysis syndrome. Your doctor will tell you to drink more water and give you medication to prevent it.
You may have venetoclax and ibrutinib for up to 2 years as long as it is helping you and the side effects aren’t too bad. If tests confirm there are no CLL cells in your blood or bone marrow you stop having them.
Samples for research
The researchers will ask you to have 4 extra bone marrow tests as part of the study. They might also ask to take extra blood tests.
Where possible you have these at the same time as your routine blood tests. The aim of these is to understand more about CLL and how to treat it.
You’ll see the doctors and have some tests before you start treatment. The tests include
You take ibrutinib at home. You may have to go to hospital and stay for a few nights for the first few doses of venetoclax if your doctor feels you need to. This is so the doctors can check that you don’t develop tumour lysis syndrome.
You see the study doctors regularly for blood tests and a check up.
You have a bone marrow test and a CT scan
- before you start having venetoclax
- at 8 weeks
- at 8 months
- at 14 months
- at 26 months
When you finish treatment the study team will follow you up for 2 years. This may be at a routine hospital visit or they might check your medical notes to see how you are getting on.
The most common side effects of ibrutinib are
- feeling or being sick
- diarrhoea or constipation
- tiredness (fatigue)
- swelling of the hands and feet
- shortness of breath
- muscle and joint pain
- common cold
- fever (high temperatures)
- skin rash
- a drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
- loss of appetite
As venetoclax is a new drug, there might be side effects that we don’t know about yet. The study team will monitor you during the time you have treatment and you will be given a phone number to call them if you are worried about anything. So far the side effects include
- feeling sick
- a drop in white blood cells (
Ibrutinib and venetoclax
Only a small number of people have had these 2 drugs together. There is a small risk that having them might cause
- tumour lysis syndrome
- an allergic reaction- this can cause a rash, breathing problems, light headedness and swelling around your mouth, throat or eyes
The doctors will keep a close eye on you and treat these side effects straight away.
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.
Professor Peter Hillmen
Experimental Cancer Medicine Centre (ECMC)
NIHR Clinical Research Network: Cancer
University of Birmingham