A trial of zilovertamab vedotin for diffuse large B cell lymphoma (waveLINE-003)
Cancer type:
Status:
Phase:
This trial is looking at zilovertamab vedotin with a 
for people with diffuse large B cell lymphoma.
You pronounce zilovertamab vedotin as zi-lov-er-ta-mab ve-dot-in.
It is open to people whose diffuse large B cell lymphoma (DLBCL) has come back after treatment (relapsed) or got worse during treatment (refractory).
More about this trial
Doctors treat DLBCL that has come back or got worse during treatment with and a .
One standard treatment is rituximab, gemcitabine and oxaliplatin (R-GemOx).
Rituximab is a monoclonal antibody that works by attaching to a protein on the cancer cell. This helps the recognise and attack the cancer cells.
Gemcitabine and oxaliplatin are chemotherapy drugs.
Zilovertamab vedotin is an . It is made up of a monoclonal antibody and chemotherapy. 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. This kills the cancer cell.
Researchers think that having zilovertamab vedotin with R-GemOx might be better than having it by itself.
The aims of the trial are to find out:
- how safe it is to have zilovertamab vedotin with R-GemOx
- how well zilovertamab vedotin with R-GemOx works
- the best dose of zilovertamab vedotin to give with R-GemOx
- more about the side effects
- how this treatment affects
quality of life
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 diffuse large B cell lymphoma (DLBCL) that continued to get worse during treatment (refractory) or came back after treatment (relapsed)
- have had at least one treatment for your DLBCL
- have had a stem cell transplant of your own stem cells (
autologous stem cell transplant ) that didn’t work or you are not able to have an autologous stem cell transplant - have a sample of tissue that the trial team can obtain a piece of tissue from
- are able to be up and about for at least half the day and can look after yourself but not be able to work (performance status 0, 1 or 2)
- are willing to use reliable contraception during treatment and for a length of time after if you or your partner could become pregnant
- have satisfactory blood test results
- are at least 18 years old
Who can’t take part
Cancer related
You cannot join this trial if any of these apply. You:
- had a low grade (indolent) lymphoma that has changed into DLBCL
- have a type of DLBCL called primary mediastinal B cell lymphoma (PMBCL)
- have active lymphoma in the brain or spinal cord. You can join if you had treatment for lymphoma in the brain or spinal cord as long as there is no sign of the lymphoma. This means the lymphoma is in remission.
- have ongoing
graft versus host disease (GvHD) or are having treatment for GvHD - have had another cancer. This is apart from successfully treated
non melanoma skin cancer , early (superficial) bladder cancer, any in situ carcinoma or any other cancer that was treated with the aim to cure and there has been no sign of it for at least the past 2 years. - have had any
systemic treatment for cancer such as chemotherapy in the past 4 weeks before joining the trial. This includes any experimental drugs as part of a clinical trial. - have ongoing moderate to severe side effects from any previous cancer treatment
- have had radiotherapy within the 4 weeks of starting trial treatment and have no ongoing side effects
Medical conditions
You cannot join this trial if any of these apply. You:
- have had an
organ transplant - have a
heart problem such as a heart attack less than 6 months ago or unstable chest pain (angina) that could affect you taking part in the trial - have had a stroke less than 6 months ago
- have fluid around the heart or around the lungs that is affecting how well you breathe
- have ongoing
peripheral nerve damage unless it is mild - have a type of
inherited disease called Charcot-Marie-Tooth (CMT) disease that damages the nerve covering of the nerves to the arms and legs (CMT types 1, 4 and X) - have had certain
targeted drug treatments. Your doctor will know which these are. - have ongoing side effects or complications from any other treatments including surgery
- are taking
steroids over a certain dose. Your doctor will know what the dose is. Your dose must also be stable for at least 4 weeks before starting treatment. - are taking medication that affects the CYP3A4 enzyme. Your doctor can tell you more about this.
- have HIV, active hepatitis C, hepatitis B or any other active infection that need treatment that reaches the whole body (systemic treatment)
- have any other medical condition, mental health problem or social problem that could affect you taking part
Other
You cannot join this trial if any of these apply. You:
- have a
live vaccine within 30 days of starting treatment. The COVID-19 and seasonal flu vaccines are not live vaccines. - are allergic or sensitive to the treatments used in the trial or any of their ingredients
- are pregnant or breastfeeding
Trial design
This is an international phase 2/3 trial. The team need about 490 people worldwide to take part with about 15 people from the UK.
There are 2 parts to this trial.
Part 1 - This part is now closed
In this part the team want to find the best dose of zilovertamab vedotin to give with rituximab, gemcitabine and oxaliplatin (R-GemOx).
The best dose is the one that works well and does not cause too many side effects or too severe side effects. To find this a few people have a small dose of zilovertamab vedotin with R-GemOx. The study team monitored people carefully to check for side effects. If this goes well. The next few have a higher dose. And so on until they find the best dose.
When they find the best dose they will use this in part 2.
Part 2
This part of the trial is randomised. A computer puts you into a treatment group. Neither you nor your doctor chooses which group you are in.
The 2 groups are:
- zilovertamab vedotin and R-GemOx
- R-GemOx
You have treatment every 3 weeks. Each 3 week period is a . You have 6 cycles of treatment for as long as it is helping and the side effects aren’t too bad.
You have zilovertamab vedotin as a drip into a vein once at the start of each treatment cycle. You have R-GemOx as a drip into a vein once at the start of each treatment cycle.
Samples for research
You give blood samples and tissue samples during the trial. Your doctor will tell you how often and when. Where possible the team will take these samples when you have them done as part of your routine care.
Researchers will use these samples to find out more about:
- zilovertamab vedotin and how it works in the body
- DLBCL and how to treat it
Hospital visits
You see the doctor for tests before taking part. These tests include:
- a
physical examination - blood tests
- scans such as a PET scan, a CT scan or an MRI scan. Your doctor will tell you which scan or scans you have.
- a bone marrow test
- a heart trace (ECG)
- a heart scan (ECHO or
MUGA )
During treatment
You see the doctor regularly for blood tests and to see how you are.
If you stopped treatment because your cancer got worse you see the doctor about a month after stopping. This is to see how you are. A member of the team will then phone you every 12 weeks to see how you are.
Follow up after finishing treatment
You see the doctor about a month after finishing treatment for blood tests and to see how you are. You then see the doctor 12 weeks later. They will tell you how often they want to see you after that.
A member of the team continues to follow up until:
- your cancer gets worse
- you start another cancer treatment or
- you decide to leave the trial
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, tiredness, bruising and bleeding
- tiredness (fatigue)
- feeling sick
- loss of appetite
- dizziness
- shortness of breath
- infection
- diarrhoea
We have more information about:
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
Professor Satyen Gohil
Supported by
Merck, Sharp & Dohme (MSD)
If you have questions about the trial please contact our cancer information nurses
Freephone 0808 800 4040
