A trial of avelumab for advanced Hodgkin lymphoma (AVENUE)

Please note - this trial is no longer recruiting patients. We hope to add results when they are available.

Cancer type:

Blood cancers

Hodgkin lymphoma

Lymphoma

Status:

Closed

This trial is looking at having avelumab before standard chemotherapy for Hodgkin lymphoma.

It is for people:

recently diagnosed with advanced Hodgkin Lymphoma
who haven’t had treatment yet

Advanced Hodgkin Lymphoma is stage 2 lymphoma with symptoms such as night sweats. Or lymphoma that is more widespread (stage 3 or stage 4).

More about this trial

Chemotherapy is the usual first treatment for people with advanced Hodgkin lymphoma. Combinations of chemotherapy you might have include:

ABVD
BEACOPP

This treatment works for some people. But sometimes the lymphoma comes back. So researchers are looking for ways to improve it.

In this trial they are looking at a drug called avelumab. It is a type of immunotherapy called a monoclonal antibody. It blocks proteins that stop the immune system from attacking the cancer cells.

So far, avelumab has only been used in people with Hodgkin lymphoma that has come back after earlier treatment.

Doctors now wonder if having avelumab before chemotherapy as a first treatment might work better. But they aren’t sure. So they are running this trial to find out more.

The main aims of the trial are to:

find out if having avelumab before chemotherapy improves the outcome of treatment
learn more about the side effects

Who can enter

The following bullet points list 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 a type of Hodgkin lymphoma called classical type and you haven’t had treatment yet
have advanced Hodgkin lymphoma (stage 2B, stage 3 or stage 4 lymphoma)
have a tumour sample (biopsy ) available for the trial team to do some tests on
have satisfactory blood test results
are well enough to carry out all your normal activities, apart from heavy physical work (performance status of 0 or 1)
are willing to use reliable contraception for 12 months after the last treatment if there is any chance you or your partner could become pregnant
are between 16 and 60 years old

Who can’t take part

You cannot join this trial if any of these apply.

Cancer related
You:

have a type of Hodgkin lymphoma called nodular lymphocyte Hodgkin lymphoma
need urgent treatment for Hodgkin Lymphoma
have had chemotherapy or radiotherapy within 15 days before joining the trial (you may take steroids but it must be possible to reduce the dose to 10mg a day for at least 7 days before having avelumab)
have had another cancer in the last 3 years apart from basal cell skin cancer , squamous cell skin cancer, thyroid cancer, CIS of the cervix or breast, stable prostate cancer or cancer that can be successfully treated with surgery
have had blood cancer in the past
aren’t suitable to have combinations of chemotherapy that include ABVD, AVD and BEACOPP
have symptoms such as breathing problems caused by the Hodgkin lymphoma

Medical conditions
You:

have an autoimmune condition apart from pale white patches on the skin (vitiligo), type 1 diabetes mellitus, thyroid problems or coeliac disease that doesn’t need treatment with a drug that damps down the immune system
have had treatment in the last 2 months that damp down the immune system apart from creams, nose sprays or low dose steroids
have had an organ transplant or a stem cell transplant with somebody else’s cells (allogeneic transplant ) in the past
have inflammation of the lung caused by past treatment (pneumonitis) or inflammation of the gut (colitis or inflammatory bowel disease)
have moderate to severe side effects from past treatment apart from hair loss or numbness in the hands or feet
have had major surgery in the 4 weeks before joining the trial
have an active infection that needs treatment
have had a heart attack, angina that isn’t well controlled with medication, a heart bypass operation, a stroke or mini stroke (TIA) in the past 6 months
are having any other medication that might interfere with having chemotherapy and avelumab
have hepatitis B or hepatitis C
have HIV
have any other medical condition or mental health problem that the trial team think would affect you taking part

Other
You:

are allergic to monoclonal antibodies
have had a live vaccination in the 30 days before starting trial treatment
are pregnant or breastfeeding

Trial design

This is a phase 2 trial. You have avelumab followed by standard chemotherapy. Treatment takes up to 8 months in total.

15565.png

Avelumab
You have avelumab as a drip into a vein. You have treatment in cycles Open a glossary item

. The first day of each treatment cycle is called day 1. You have treatment on:

day 1
day 15

This takes about 2 months. You then have a PET-CT Open a glossary item scan and a CT scan to see how treatment worked. Everyone then has standard chemotherapy.

Standard chemotherapy
This includes the following combinations:

ABVD
AVD (this is ABVD without bleomycin)
BEACOPP

ABVD includes the drugs:

doxorubicin (Adriamycin)
bleomycin
vinblastine
dacarbazine

Everyone has ABVD to begin with. You have it as a drip into a vein. Each 4 week period is a cycle of treatment. You have 2 cycles of ABVD. This takes about 2 months.

You then have a PET-CT scan to see how treatment worked. If treatment works (a negative scan) you stop bleomycin and have AVD.

If treatment doesn’t work (a positive scan) you have a combination of chemotherapy called BEACOPP.

AVD (a negative scan)
If ABVD treatment works you have a combination of chemotherapy called AVD. This includes the drugs doxorubicin, vinblastine and dacarbazine. You have 4 cycles of treatment. This takes about 4 months.

You then have a CT scan.

BEACOPP (a positive scan)
If ABVD treatment doesn’t work you have a combination of chemotherapy called BEACOPP. This is more intensive chemotherapy. There are 2 different schedules for having this. The schedule you have depends on where you are having treatment. The trial doctor can tell you more about this. Treatment takes between 8 and 9 weeks.

BEACOPP includes the drugs:

bleomycin
etoposide
doxorubicin (also called Adriamycin)
cyclophosphamide
vincristine (also called Oncovin)
procarbazine
prednisolone (a steroid)

After BEACOPP you have a PET-CT scan. If treatment worked you have 1 or 2 more cycles of BEACOPP. If treatment didn’t work you won’t have any more treatment as part of this trial. Your doctor will talk to you about other treatment options.

Some people might have radiotherapy as part of their treatment. The doctor will tell you more about this if they think you need it.

Samples for research
The researchers ask for a sample of your lymphoma (a biopsy Open a glossary item ) from when you were first diagnosed. 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 how well treatment is working
look at genes to help understand more about Hodgkin Lymphoma
look for biomarkers to predict who will benefit from treatment

You do not have to agree to give some of these samples if you don’t want to. You can still take part in the trial. They researchers might ask to store any leftover samples for future research.

Hospital visits

You see a doctor and have some tests before you join the trial. These include:

physical examination
blood tests
urine test
heart trace or ECHO
breathing tests (lung function tests)
PET-CT scan
CT scan

You have treatment at hospital on the day ward.

When you finish treatment you see the doctor for a check up and blood tests:

every 3 months for up to 1 year
once a year for a further 3 years

This follow up can vary a bit and depends on when you joined 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.

Avelumab can affect the immune system. It may cause inflammation in different parts of the body which can cause serious side effects. They could happen during treatment, or some months after treatment has finished. Rarely, these side effects could be life threatening.

If you have any of these side effects, you should tell the doctor or nurse as soon as possible. You should tell them that you are on or have been on an immunotherapy.

The most common side effects of avelumab are:

diarrhoea or constipation
stomach pain
feeling or being sick
loss of appetite
high temperatures
swelling in the body
weight gain
back and joint pain
cough
a drop in red blood cells (anaemia ) causing tiredness, dizziness and shortness of breath

You might have an allergic reaction to avelumab. This might happen during the infusion, causing a skin rash, itching, swelling of the lips, face or throat, breathing difficulties or fever and chills. Your nurse will keep a close eye on you and treat any problems immediately.

The most common side effects of ABVD, AVD and BEACOPP include:

an increased risk of infection,
an increased risk of bleeding and bruising
tiredness
fever
lung problems (pneumonitis) with signs and symptoms that might include a new or worsening cough, shortness of breath and chest pain
blood clots
tingling, numbness or weakness of the hands or feet

We have more information about the side effects of: