A trial looking at nemtabrutinib, ibrutinib or acalabrutinib for chronic lymphocytic leukaemia or small lymphocytic lymphoma (BELLWAVE-011)

Cancer type:

Blood cancers
Chronic leukaemia
Chronic lymphocytic leukaemia (CLL)
Low grade lymphoma
Non-Hodgkin lymphoma




Phase 3

This trial is comparing nemtabrutinib with ibrutinib or acalabrutinib for chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL). 

It is for people who haven’t yet had treatment for CLL or SLL. 

You pronounce nemtabrutinib as nem-ta-broo-ti-nib. 

More about this trial

Chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) are types of blood cancer. The treatments for CLL and SLL are the same. 

You might have ibrutinib or acalabrutinib to treat CLL or SLL. These are targeted cancer drugs Open a glossary item called bruton tyrosine kinase inhibitors (BTKi). They stop signals that cancer cells use to divide and grow. 

Researchers are looking for new treatments for CLL or SLL. In this trial they are looking at a new drug called nemtabrutinib (MK-1026). It is similar to ibrutinib and acalabrutinib, but it works in a slightly different way. 

Doctors aren’t sure how well nemtabrutinib will work for CLL or SLL so they are doing this trial to find out more. In this trial some people have nemtabrutinib. And some people have ibrutinib or acalabrutinib. 

The main aims of the trial are to find out:

  • how safe it is to have nemtabrutinib for CLL or SLL 
  • how well nemtabrutinib works compared to ibrutinib or acalabrutinib
  • what the side effects are

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 CLL or SLL that needs treatment. Your doctor will know this. 
  • have swollen lymph nodes Open a glossary item that measure more than 1.5cm across on a CT or MRI scan, the number of platelets Open a glossary item or red blood cells Open a glossary item in your blood is getting lower or the number of white blood cells Open a glossary item in your blood is getting higher. Your doctor will know this. 
  • have changes in the TP53 gene Open a glossary item or part of chromosome 17 is missing (deleted). Your doctor will know this. 
  • can swallow medication and keep it down 
  • have satisfactory blood test results 
  • are up and about for at least half the day. You can look after yourself but might not be able to work (performance status of 0, 1 or 2). 
  • are willing to use reliable contraception during the trial and for a time after if there is any chance you or your partner could become pregnant 
  • are at least 18 years old 

Who can’t take part

Cancer related 
You cannot join this trial if any of these apply. You:

  • have already had cancer treatment that reaches the whole body (systemic cancer treatment Open a glossary item) for CLL or SLL 
  • have Richter’s syndrome or Richter’s transformation. Your doctor will know this.
  • have CLL or SLL that has spread to the brain or spinal cord 
  • have had recent radiotherapy or any radiotherapy side effects that need steroid treatment Open a glossary item. You can take part if you had radiotherapy to help with symptoms and it wasn’t treatment to the brain.
  • are taking an experimental drug or using a device as part of another clinical trial. This is if it is within 4 weeks of being put into a treatment group for this trial.
  • have had another cancer in the last 2 years unless it has been successfully treated and there have been no signs of it since. You can join if you have non melanoma skin cancer Open a glossary item or carcinoma in situ Open a glossary item. This doesn’t apply if you have CIS of the bladder. 

Medical conditions
You cannot join this trial if any of these apply. You:

  • have a problem with your digestive system (gut) that means you can’t absorb medication 
  • have a problem with your heartbeat. The trial team check if you have a heart condition before you join the trial. 
  • have a severe bleeding problem 
  • have a problem with how your immune system Open a glossary item works or you have had treatment that damps down the immune system. This includes steroid treatment within 2 weeks of starting trial treatment unless it was a low dose.
  • have an autoimmune condition Open a glossary item that needed treatment in the last 2 years apart from certain ones. Your doctor will know about this. 
  • are taking medication that affects body substances called CYP enzymes. Your doctor will know this. 
  • have HIV unless you are having treatment and it is under control. You can’t take part if you have HIV and you developed an illness that occurs more often and is more severe in people with HIV.
  • have active hepatitis B or hepatitis C unless you have had or are having treatment and it is under control or you have another active infection that needs treatment
  • have had major surgery and you aren’t better yet
  • have any other medical condition or mental health problem that could affect you taking part in the trial

You cannot join this trial if any of these apply. You:

  • are pregnant or breastfeeding 
  • are allergic to nemtabrutinib or you can’t have ibrutinib or acalabrutinib for any reason 
  • have had a live vaccine Open a glossary item within 30 days of starting trial treatment. Please note that the COVID-19 vaccine is allowed as it isn’t a live vaccine.
  • have a problem with drugs or alcohol 

Trial design

This phase 3 trial is taking place worldwide. The team need to find 1,200 people to take part including 56 people from the UK. 

It is a randomised trial. A computer puts you into a treatment group. Neither you nor your doctor will be able to decide which group you are in. 

There are 2 treatment groups. You have 1 of the following:

  • nemtabrutinib (group 1)
  • ibrutinib or acalabrutinib (group 2)

Everyone has treatment for as long as it is working and the side effects aren’t too bad. 

Nemtabrutinib (group 1)
Nemtabrutinib is a tablet. You take it once a day, every day. The trial doctor tells you how many tablets to take. 

Ibrutinib or acalabrutinib (group 2)
You and your doctor talk about whether you should have ibrutinib or acalabrutinib. You have the drug that they think will work best for you.

Acalabrutinib is a tablet. You take it twice a day, every day  

Ibrutinib is a tablet. You take it once a day, every day.

The trial doctor tells you how many tablets to take.

Samples for research 
The researchers ask to look at samples of tissue taken from your lymph nodes Open a glossary item or bone marrow tests Open a glossary item. They also ask to take some extra blood samples. Where possible, you have these at the same time as your routine blood tests.

They plan to use the samples to:

  • see what happens to treatment in the body 
  • see how well the treatment is working
  • look at genes Open a glossary item to understand more about SLL and CLL
  • look for substances called biomarkers Open a glossary item to help work out why treatment might work for some people and not for others

If there is any remaining blood from the samples, the team will ask to store this away for future research. You don’t have to agree to your samples being stored. You can still take part in the trial.

Quality of life
The trial team ask you to fill out some questionnaires:

  • before you start treatment
  • at set times during treatment
  • at set times after treatment 

The questionnaires ask about side effects and how you’ve been feeling. This is called a quality of life study.

Hospital visits

You see the doctor and have tests before you can take part. These include:

You might also have a sample of tissue (biopsy) taken from a swollen lymph node if you have this. 

You see the trial doctor regularly during treatment. This is for blood tests and to see how you are. 

You have tests every 3 months during treatment to see how well it is working. These might include scans or bone marrow tests. The trial team can tell you more about the scans or tests you might have. 

The team also ask you to have another bone marrow test if they suspect that your SLL or CLL has gone away completely.

Follow up visits
When you stop treatment, you see the trial team one month later for a check up. 

The team then follow you every 3 months. You might see them at a routine hospital appointment. Or they may call you to see how you are getting on or check your medical notes.

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 nemtabrutinib include:

We have more information about the following drugs and their side effects: 

Your doctor will talk to you about all the possible side effects of treatment. You’ll have a chance to ask them any questions you may have.



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.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Toby Eyre

Supported by

Merck Sharp & Dohme LLC

If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:


Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Last reviewed:

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