A trial of rituximab and varlilumab for people with B cell lymphoma (RiVa)

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

Cancer type:

Blood cancers
High grade lymphoma
Low grade lymphoma
Non-Hodgkin lymphoma




Phase 2

This trial is for people with a type of lymphoma that affects the B cells (B cell lymphoma) that has either:

  • come back (relapsed)
  • continued to grow despite treatment (refractory)

It is for people who have a protein called CD20 on the surface of their lymphoma cells (CD20 positive). 

Cancer Research UK supports this trial.

More about this trial

Lymphoma is a type of cancer that starts in the lymphatic system. B cell lymphoma is a lymphoma that starts in a particular type of white blood cell called a B lymphocyte. There are different types of B cell lymphoma such as:

  • diffuse large B cell lymphoma (DLBCL)
  • follicular lymphoma
  • mantle cell lymphoma

You usually have a combination of chemotherapy and targeted cancer drugs (biological therapy) for B cell lymphoma. The exact treatment depends on which type of lymphoma you have. One of the possible treatments is a combination of cancer drugs called R-CHOP.

Sometimes lymphoma comes back after treatment (relapses), or continues to grow despite treatment (refractory). You usually have more chemotherapy if this happens.

In this trial, doctors are looking at combining two drugs. The drugs are rituximab and a new drug called varlilumab.

Rituximab (Mabthera) is a type of immunotherapy called a monoclonal antibody. It targets a protein called CD20 on the surface of the lymphoma cells. Rituximab is already used to help people with relapsed or refractory lymphoma.

Varlilumab is also a monoclonal antibody. It targets the CD27 protein.

Doctors think that varlilumab together with rituximab might help people with relapsed or refractory B cell lymphoma.

The main aims of this trial are to:

  • find out how well rituximab and varlilumab work as a treatment for B cell lymphoma
  • learn 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 B cell lymphoma that has come back (relapsed) or continued to grow despite treatment (refractory)
  • have the protein CD20 on the surface of lymphoma cells (CD20 positive)
  • have had at least 1 type of treatment for B cell lymphoma
  • have at least 1 area of lymphoma that can be seen on a scan and measures at least 15 mm
  • have at least 1 area of cancer that doctors can safely take a sample of tissue (biopsy) from
  • are well enough to be up and about for at least half of the day (performance status 0,1 or 2)
  • have satisfactory blood test results
  • are willing to use reliable contraception during treatment and for 12 months afterwards if there is any possibility you or your partner could become pregnant
  • are at least 16 years old 

Who can’t take part
You cannot join this trial if any of these apply.

Cancer related

  • you have chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL)
  • your lymphoma has spread to the brain, unless you have had treatment and there is no sign of it anymore (remission)
  • you have had another cancer in the last 2 years, unless it was an early cancer (carcinoma in situ) of the breast, cervix, prostate, or non melanoma skin cancer that has been successfully treated
  • you have had chemotherapy or immunotherapy in the last month
  • you have had radiotherapy in the last 2 weeks

Medical conditions

  • still have side effects from previous treatment apart from hair loss or any other mild side effect that the trial team thinks will not affect you taking part
  • have had drugs that damp down your immune system (immunosuppressant) in the last 2 weeks, unless it was a cream or a very small dose
  • have had a donor transplant (allogeneic transplant)
  • have had a bone marrow transplant in the last 100 days (around 3 months)
  • have an autoimmune disease such as inflammatory bowel disease (IBS), coeliac disease or haemolytic anaemia
  • have heart problems such as congestive heart failure, an abnormal heart beat (arrhythmia) or angina that isn’t controlled
  • have had a heart attack in the last 6 months 
  • have an active infection
  • have HIV
  • have hepatitis B or hepatitis C
  • have any other medical condition that the trial team think could affect you taking part


  • are pregnant or breastfeeding
  • are sensitive to rituximab or any other similar drug

Trial design

This is a phase 2 trial. Researchers hope that around 40 people from the UK will take part.  

There are 2 groups (arms) in this trial:

  • arm A
  • arm B

Both groups have rituximab and varlilumab. But when you have varlilumab is different between the 2 groups. The group you go to is decided at random by a computer. This is called a randomised trial.

You have both drugs in cycles of treatment. Each cycle of treatment lasts 2 weeks. The 1st day of each cycle is called day 1. You have up to 6 cycles of treatment in total. It takes about 3 months.

People in group A have the 1st cycle of treatment in the following way. You have:

People in group B have the 1st cycle of treatment in the following way. You have:

  • rituximab as a drip into your bloodstream on day 1
  • no treatment from day 2 to day 7
  • varlilumab as a drip into bloodstream on day 8
  • no treatment for 6 days

Then both groups have treatment in the following way:

  • rituximab on day 1 of each cycle of treatment
  • varlilumab on day 2 of cycle of treatment 3 and 5

RiVa Diagram

Blood tests
You have extra blood tests as part of this trial. Researchers want to find out what happens to rituximab and varlilumab in your body (pharmacokinetics).

You have the extra blood tests before treatment and at set times during the trial.

Sample of tissue
The trial team asks you to give samples of tissue (biopsies). Researchers want to look at the cancer cells and the effect the treatment has in your body.

You have a biopsy:

  • before the start of treatment
  • on day 8 of the first cycle (cycle 1) 

Hospital visits

You see a doctor and have some tests before taking part. These tests might include:

During treatment, you see the trial doctor regularly for blood tests and a physical examination. Your doctor can tell you how often you see them. 

You see the trial team 2 weeks after finishing treatment. You have a blood test and a physical examination. You also have a CT scan or PET-CT scan.

You then see the trial team every 2 months, for up to a year.

Side effects

The trial team monitors you during the time you have treatment and afterwards. They give you a phone number to call them if you are worried about anything.

The team will tell you about all the possible side effects before you take part. The most common side effects of varlilumab are:

We have information about the possible side effects of rituximab.

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.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Sean Hua Lim

Supported by

Cancer Research UK
University of Southampton
University Hospital Southampton NHS Foundation Trust

Other information

This is Cancer Research UK trial number CRUKD/17/008.

Freephone 0808 800 4040

Last review date

CRUK internal database number:


Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Around 1 in 5 people take part in clinical trials

3 phases of trials

Around 1 in 5 people diagnosed with cancer in the UK take part in a clinical trial.

Last reviewed:

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