A trial looking at zilovertamab vedotin by itself or with nemtabrutinib for B cell lymphoma and B cell leukaemia (waveLINE-006)
Cancer type:
Status:
Phase:
This trial is looking at zilovertamab vedotin by itself or in combination with nemtabrutinib for people with B cell lymphomas and B cell leukaemia.
B cell lymphoma and B cell leukaemia are also called B cells cancers.
It is open to people with one of the following B cell cancers that has come back or got worse during treatment:
- mantle cell lymphoma
- follicular lymphoma
- chronic lymphocytic leukaemia
- Richter transformation . This is also called Richter’s syndrome.
You pronounce zilovertamab vedotin as zi-lov-er-ta-mab ve-dot-in.
You pronounce nemtabrutinib as nem-tab-rut-i-nib.
More about this trial
Researchers are always looking for new treatments that doctors can use to treat B cell cancers. They think that zilovertamab vedotin by itself or in combination with nemtabrutinib might help.
Zilovertamab vedotin is an 
. It is made up of a and . Zilovertamab is the monoclonal antibody. It attaches to the cancer cell. Vedotin is a chemotherapy. Once zilovertamab is attached to the cancer cell it releases the vedotin into the cancer cell. The vedotin kills the cancer cell.
Nemtabrutinib is a called a cancer growth blocker. It blocks signals that cancer cells use to divide and grow.
In this trial some people will have:
- zilovertamab vedotin by itself
- zilovertamab vedotin with nemtabrutinib
The main aims of this trial are to find out:
- how safe it is to have zilovertamab vedotin by itself and with nemtabrutinib
- how well zilovertamab vedotin by itself works for B cell cancers
- how well zilovertamab vedotin with nemtabrutinib works for B cell cancers
- more about the side effects of treatment
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 you have one of the following B cell cancers:
And all of the following apply.
- Your B cell cancer came back after treatment (relapsed) or got worse during treatment (refractory). Your doctor will know about this.
- You have had at least 1 and no more than 2 certain treatments for your B cell cancer. Your doctor will know which treatments these are and how many you have had.
- You have an area of cancer the doctor can measure on a scan. The doctor checks the size of the cancer to see if you are suitable to take part. You might be able to join if you have follicular lymphoma or chronic lymphocytic leukaemia and you have symptoms that mean you need treatment even if an area of cancer can’t be measured on a scan. Your doctor can explain this.
- You are willing to use reliable contraception during treatment and for a time after if there is any chance you or your partner could become pregnant.
- There is a sample of tissue (
biopsy ) that the team can assess and is suitable for the team to use. - You can look after yourself but might not be able to work (performance status 0, 1 or 2) within the week before starting treatment. Your doctor will assess this.
- You have satisfactory blood test results.
- You 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 or had lymphoma in the brain or spinal cord. If you had lymphoma in the brain or spinal cord you could join if there is no sign of it (that means it is in remission).
- have follicular lymphoma that has changed into a lymphoma that grows more quickly (that means it is more aggressive)
- have had a stem cell transplant from a donor (
allogeneic transplant) and have graft versus host disease (GvHD). If you have ongoing GvHD (chronic) that is mild (grade 1) you might be able to take part. Your doctor will know more about this. - are taking part in a clinical trial, or have taken part within 4 weeks of starting treatment, using an experimental drug or device
- have radiotherapy within 4 weeks of starting treatment. For radiotherapy to relieve symptoms it is 2 weeks as long as it did not treat the brain or spinal cord.
- have ongoing side effects from radiotherapy
- have had certain cancer treatments such as
monoclonal antibodies that reach the whole body within a certain time before starting the trial treatment. Your doctor will know about this. - have had a
targeted drug that works in the same way as the trial treatments. Your doctor will know about this. - have or had another cancer unless it was treated with the aim to cure and there has not been any sign of it for 2 years. This is apart from successfully treated
non melanoma skin cancer , superficial (non muscle invasive) bladder cancer or any in situ carcinomas such as in situ carcinoma of the cervix.
Medical conditions
You cannot join this trial if any of these apply. You:
- have had an
organ transplant - have had a stroke in the past 6 months
- have had a
heart problem such as a heart attack or unstable chest pain (unstable angina) in the past 6 months or any other heart problem that could affect you taking part - have a problem with your
digestive system that could affect how you absorb medication - have fluid around the heart
- have fluid on the lungs that is causing symptoms or needs treatment
- have ongoing damage to the nerves (peripheral neuropathy) unless it is mild
- have an
inherited disease called Charcot-Marie-Tooth disease that affects the covering of nerves in the teeth - are taking a dose of more than 30mg of
steroids a day. If you are taking smaller dose of steroids the dose must be the same for at least 4 weeks before starting trial treatment. This is unless it is to control lymphoma symptoms, such as dexamethasone, than it can be up to 100mg a day for up to 5 days. - are taking medication or herbal preparations that affect the CYP enzymes
- have HIV, active hepatitis B, active hepatitis C or any other active infection that needs treatment that reaches the whole body (systemic treatment)
- have any other medical condition, mental health problem or any other problem that could affect you taking part
Other
You cannot join this trial if any of these apply. You:
- are allergic or sensitive to the treatments in this trial or any of their ingredients
- have a
live vaccine within 30 days of starting trial treatment. The COVID-19 and seasonal flu vaccines are not live vaccines. - are pregnant or breastfeeding
Trial design
This is an international phase 2 trial. The team need about 275 people to take part with 9 people in the UK.
There are 6 groups in this trial. Which group you go into depends on which type of B cell cancer you have and previous treatment. Whether you have zilovertamab vedotin by itself or with nemtabrutinib depends on which group you are in.
You have zilovertamab vedotin as a drip into a vein. You have treatment every 3 weeks. Each 3 weeks is a . Depending on the dose, you have treatment either on day 1 of each cycle or days 1 and 2 of each cycle.
Nemtabrutinib is a tablet. You take it once a day every day. Your doctor will tell you how many tablets to take.
You continue having treatment as long as it is working and the side effects aren’t too bad.
Quality of life
You fill in questionnaires:
- before starting treatment
- during treatment
- after treatment
The questions ask about:
- your general health and wellbeing
- your daily activities
- side effects
These are quality of life questionnaires.
Samples for research
The team take blood samples and tissue samples for research. Where possible they will take these samples when they are taken as part of your routine care.
They will use these samples to:
- look for substances (
biomarkers ) that might show how well treatment is working - see whether your genes affect how well the treatment works
- see what happens to the treatments in the body and how they affect the body
- learn more about B cell cancers
Optional samples for research
The trial will ask your permission to use the samples they take for future research. You don’t have to agree to this.
Hospital visits
You see a doctor and have some tests before you join the trial. These might include:
- a
physical examination - blood tests
- urine tests
- CT scan or PET scan
- heart trace (ECG) or heart scan (
MUGA scan )
You might also have a bone marrow test.
You see the doctor regularly during treatment to see how you are and for blood tests.
You have a PET scan and CT scan every 12 weeks.
You see the doctor 30 days after stopping treatment. They check how you are and you have blood tests.
Follow-up
You see the doctor every 3 months. They will check how you are.
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.
Zilovertamab vedotin is a new drug and there might be side effects we don’t know about yet. The most common side effects reported are:
- nerve damage causing tingling, numbness or weakness in the arms and legs or both (peripheral neuropathy)
- a drop in blood cells causing an increased risk of infection, bruising and bleeding
- tiredness
- feeling sick
- loss of appetite
- dizziness
- shortness of breath
- infection
- diarrhoea
- sore muscles
Nemtabrutinib is a new drug and there might be side effects we don’t know about yet. The most common side effects reported are:
- taste changes
- tiredness
- feeling weak
- feeling sick
- a drop in blood cells causing an increased risk of infection, bruising and bleeding
- diarrhoea or constipation
- skin rash
Your doctor will discuss with you the possible side effects of the treatments and answer any questions you have before you agree to take part.
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
Merck Sharp & Dohme
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
