A trial of zanubrutinib for lymphoma of the brain and spinal cord (PRiZM+)

Cancer type:

Blood cancers

Brain (and spinal cord) tumours

High grade lymphoma

Lymphoma

Non-Hodgkin lymphoma

Status:

Open

Phase:

Phase 2

This trial is looking at zanubrutinib for primary central nervous system lymphoma Open a glossary item .

It is open to people whose lymphoma is a diffuse large B cell lymphoma Open a glossary item and has:

got worse during treatment or
come back after treatment

More about this trial

Primary central nervous system lymphoma (PCNSL) is a type of brain tumour. The most common type of PCNSL is diffuse large B cell lymphoma (DLBCL).

Doctors can treat PCNSL with high doses of chemotherapy. Unfortunately for some people this doesn’t help and their lymphoma continues to get worse during treatment. For others the treatment helps but their lymphoma comes back sometime after they have finished treatment.

Researchers are looking for other treatments to help people in these situations.

Zanubrutinib is a targeted drug Open a glossary item called a cancer growth blocker. It targets a particular enzyme that DLBCL needs to grow and divide. By doing so it stops the DLBCL from growing.

Other studies show that similar drugs to zanubrutinib can help people with PCNSL. Researchers want to find out if zanubrutinib can improve treatment.

The aims of the trial are to find out:

how well zanubrutinib works for PCNSL
what happens to zanubrutinib in the body
how zanubrutinib affects the body
more about the side effects

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 primary lymphoma of the brain and spinal cord that is a diffuse large B cell lymphoma (DLBCL) and has the CD20 protein. Your doctor will know if your lymphoma has this protein.
have had treatment and the lymphoma continued to get worse during treatment or came back after treatment
have lymphoma that the doctor can measure on an MRI scan
are up and about for more than half the day, can look after yourself but might not be able to work (performance status 0, 1 or 2). You might be able to join if because of the lymphoma you need help to look after yourself (performance status 3).
are able to swallow capsules
have satisfactory blood test results
are willing to use contraception during the trial and for a time after if there is any chance you or your partner could become pregnant
are able to give informed consent . If you are not able to give informed consent due to the effects of the lymphoma a legal representative can do so on your behalf. Talk to your doctor or the trial team about this.
are at least 16 years old

Who can’t take part

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

have or have had lymphoma in another part of the body
have lymphoma that is only in the eye
had chemotherapy for lymphoma within 2 weeks of starting zanubrutinib
had radiotherapy to the whole of the brain within 4 weeks of starting zanubrutinib
have already had a drug that works in the same way as zanubrutinib. Your doctor will know if you have.
had another cancer in the past 2 years. This is apart from non melanoma skin cancer , carcinoma in situ of the breast or cervix or early prostate cancer (stage T1a or T1b) that was found due to looking at another health problem.

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

are not able to have a lumbar puncture
have an active infection that needs treatment through a drip into a vein (intravenous infusion )
have a bleeding problem such as haemophilia or severe Von-Willebrand disease
are taking warfarin or you are taking 2 treatments to prevent blood clots. You can join if you are taking another treatment to prevent blood clots such as dabigatran and rivaroxaban or low molecular heparin. Ask your doctor about this if you are taking medication to thin the blood.
have HIV. You might be able to join if you are taking anti retroviral drugs and blood tests show the HIV is undetectable. You need to talk to your HIV doctor about this.
have hepatitis B. You might be able to join if blood tests show there is no sign of the virus in your blood. You need to talk to your doctor about this.
have hepatitis C
have heart problems or breathing problems that your doctor thinks could affect you taking part

Other
You cannot join this trial if you are pregnant or breastfeeding.

Trial design

This is a phase 2 trial. The team need 20 people to take part.

Zanubrutinib is a capsule. You take it twice a day every day. You take 2 capsules unless your doctor tells you otherwise. You can take them with or without food.

Your doctor will talk to you about taking zanubrutinib and what to do if you accidentally miss a dose.

You continue to take zanubrutinib as long as it is helping and the side effects aren’t too bad.

Samples for research
You give extra blood samples during the trial. Where possible the trial team take these when you have bloods taken as part of your routine care.

The team will ask for samples of the fluid surrounding the brain and spine (CSF) when you have the lumbar puncture Open a glossary item .

They also ask for a piece of the lymphoma tissue (biopsy Open a glossary item ) from when you were first diagnosed or from when the lymphoma came back. You do not have a new biopsy done. The team can get these samples from the hospital where they were taken.

Researchers will or plan to use these samples to:

see what happens to zanubrutinib in the body
find out how zanubrutinib affects the body
look for small pieces of lymphoma DNA (ctDNA ) in the blood and CSF
find out more about primary lymphoma of the brain and spine

MRI scan for research
The team are looking at whether a certain type of MRI scan Open a glossary item is better than the routine MRI scan to look at primary CNS lymphoma. Depending on which hospital you go to you might have an MRI scan for this research. It is no different to having a routine MRI scan.

Hospital visits

You see the doctor for tests before taking part. These tests include:

a physical examination
blood tests
lumbar puncture
an examination to see how well your brain and nervous system is working (neurological examination)
an MRI scan of the brain and spine
eye examination
PET-CT scan or CT scan
heart trace (ECG )

You see the doctor regularly during the first 3 months of treatment. This is to:

see how you are
take blood tests
find out if you are having any side effects

You then see the doctor every 3 months.

You have an MRI scan every 3 months.

You have a lumbar puncture after the start of treatment at:

1 week
2 weeks
4 weeks
8 weeks

At the end of treatment you see the doctor for a check up and blood tests. You also have:

a neurological examination
an MRI scan

You then continue to see the doctor every 3 months.

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 zanubrutinib are:

a drop in blood cells causing an increased risk of infection, bleeding and bruising
infections such as lung infections, urine infections, skin infection (cellulitis), flu and shingles
skin rash
muscle and bone pain
diarrhoea or constipation
cough
tiredness (fatigue)
blood in the urine
another cancer
headache
feeling sick
high temperature (fever)
high blood pressure