A trial of Zevalin for older people with diffuse large B cell lymphoma (ZEST study)

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

Cancer type:

High grade lymphoma

Lymphoma

Non-Hodgkin lymphoma

Status:

Closed

Phase:

Phase 3

This trial is looking at Zevalin (also called ibritumomab tiuxetan) for people over 60 with a type of non Hodgkin lymphoma called diffuse large B cell lymphoma. The people taking part have been diagnosed recently, but their lymphoma has completely disappeared after having treatment such as R-CHOP.

Diffuse large B cell lymphoma (DLBCL) is the most common type of high grade non Hodgkin lymphoma. Doctors often treat DLBCL with chemotherapy and a drug called rituximab. This treatment is known as R-CHOP.

If your lymphoma has completely disappeared after treatment (a complete response Open a glossary item ), you don’t need to have any further treatment. But your doctors will keep a close eye on you to look for any signs of the lymphoma coming back. This is called observation and is standard treatment for DLBCL that has completely disappeared.

In this trial, researchers are looking at a drug called Zevalin. It is a type of biological therapy called a monoclonal antibody with a radioactive substance called yttrium (pronounced it-tree-um) attached to it.

The monoclonal antibody recognises a protein on lymphoma cells. It sticks to the protein and delivers radiation directly to these cells.

In this trial, researchers are comparing Zevalin with the standard treatment of observation. The aims of the trial are to see

Whether Zevalin is better than observation for people with diffuse large B cell lymphoma that has responded to chemotherapy and rituximab
What the side effects are

Who can enter

You may be able to enter this trial if you

Are at least 60 years old
Have diffuse large B cell lymphoma that was stage 2, 3 or 4 when it was diagnosed, or follicular lymphoma that was stage 3B when it was diagnosed – your doctor can confirm this
Have had chemotherapy and rituximab
Have had a PET scan following treatment that shows the lymphoma has completely disappeared (a complete response )
Are well enough to be up and about for at least half the day (performance status 0, 1 or 2)
Have satisfactory blood and bone marrow test results
Are willing to use reliable contraception during the trial and for a year afterwards if you are a man and there is any chance your partner could become pregnant

You cannot enter this trial if you

Have had another treatment that includes a radioactive substance or any other type of treatment for lymphoma, apart from chemotherapy and rituximab
Had lymphoma cells in your brain or spinal cord (central nervous system), or in your testicles when you were diagnosed
Were diagnosed with low grade lymphoma in the past and this has changed (transformed) into high grade lymphoma
Haven’t recovered from side effects of chemotherapy, unless they are very mild
Have had a growth factor for blood cells in the last 4 weeks, or you needed to have one more than 8 weeks after your last dose of chemotherapy
Have had an experimental drug in the last 4 weeks
Have had major surgery in the last 4 weeks
Have problems with your liver or kidneys
Have had a heart attack in the last 6 months or have any other serious medical condition that could affect you taking part
Have had any other cancer in the last 5 years, unless it was a very early stage and has been successfully treated
Take steroids unless this is a low dose of prednisolone that you take for another medical condition and the dose has been stable for at least 4 weeks – you can take steroids to prevent an allergic reaction if needed
Are known to be very sensitive to drugs made in a similar way to Zevalin
Are known to have HIV, hepatitis B or hepatitis C

Trial design

This international phase 3 trial will recruit nearly 500 people. It is a randomised trial. The people taking part are put into treatment groups by a computer. Neither you nor your doctor will be able to decide which group you are in.

Half the people taking part have Zevalin. The other half have observation, which is currently the standard treatment Open a glossary item for people with DLBCL who have had a complete response to chemotherapy and rituximab.

ZEST study

If you are in the Zevalin group, you also have 2 more doses of rituximab. You have the 1st dose on its own through a drip into a vein. The following week you have another dose of rituximab. And then 4 hours later you have the Zevalin. You have this just once, through a drip into a vein.

If you are in the observation group, you don’t have any more treatment unless your lymphoma comes back.

Hospital visits

You see the trial team and have some tests before you are put into a treatment group. The tests include

Physical examination
Blood tests
Heart trace (ECG )

If you are in the Zevalin group, you go to hospital in weeks 1, 2, 4, 7, 12 and 13. You have rituximab in week 1. You have rituximab and Zevalin in week 2.

You have weekly blood tests for the first 3 months. You may need to have another bone marrow test if you didn’t have one after finishing chemotherapy.

If you are in the observation group, you see the doctor and have blood tests twice in the first 3 months.

After the first 3 months, people in both groups see the trial team every 3 months for 2 years and then every 6 months up to year 5. At each visit, you have a physical examination and blood tests. The trial team will ask you about your health and about any medication you are taking.

Everybody taking part has a CT scan every 3 months for the first year and every 6 months in the 2nd year. After that, your doctor will decide how often you need to have a scan.

If you have symptoms that could mean your lymphoma has come back, you may have a CT scan at another time. If your lymphoma does come back, your doctor will talk to you about your treatment options. You will no longer need to have the hospital visits or CT scans for this trial.

Side effects

The most common side effects of Zevalin are

A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
Feeling sick
Weakness, high temperature (fever) and chills
Tiredness (fatigue)

The most common side effects of rituximab include

Itching, redness or pain at the site where you have the drip
A drop in blood cells causing an increased risk of infection, bleeding problems, tiredness and breathlessness
High temperature (fever) and chills
An allergic reaction to the drug
Feeling sick
Skin rash and itching
Bald spots on your scalp
Headache
Weakness

We have more information about Zevalin and rituximab in our cancer drugs section.