Purpose of trial
The aim of this trial is to test the safety and effectiveness of the combination of varlilumab and rituximab for people with B-cell NHL that has come back (relapsed) or didn’t respond (refractory) to at least two previous lines of treatment.
Two different groups are being treated as part of the trial:
- People with high-grade (fast-growing) lymphoma: diffuse large B-cell lymphoma, fast-growing (grade 3b) follicular lymphoma, and follicular lymphoma that has transformed (changed) into a faster-growing lymphoma.
- People with low-grade (slow-growing) lymphoma: follicular lymphoma grade 1, 2 or 3a, marginal zone lymphoma (MALT lymphoma, splenic marginal zone lymphoma and nodal marginal zone lymphoma), mantle cell lymphoma and Waldenström’s macroglobulinaemia or other types of lymphoplasmacytic lymphoma.
Varlilumab is a new antibody treatment that can help to activate your immune system to destroy lymphoma cells.
Everyone in this study has both rituximab and varlilumab but is randomly allocated to one of two dosing schedules.
In each schedule, everyone has 6 cycles of treatment with rituximab given on day 1 of each cycle. A cycle of treatment is 14 days. Varlilumab is given on day 2 of each cycle, with the exception of cycle 1:
- Group A has varlilumab on day 2 of cycle 1.
- Group B has varlilumab on day 8 of cycle 1. This group therefore have a gap of 7 days between rituximab being given and varlilumab being given, in cycle 1.
Everyone in the trial has a biopsy on day 7 or 8 of cycle 1. If you are in group B, the sample is taken before you have your first dose of varlilumab. This is to allow the researchers to understand the effects of varlilumab on the tumour itself.
Participants are recruited slowly to this trial, so the safety of the treatment can be monitored in a small number of people to start with.
Who can enter
Your consultant can give you advice on whether this trial might be suitable for you.
Around 40 people are needed for this trial.
You may be able to enter if:
- You have relapsed or refractory B-cell non-Hodgkin lymphoma (diffuse large B-cell lymphoma, follicular lymphoma, transformed follicular lymphoma, marginal zone lymphoma [MALT lymphoma, splenic marginal zone lymphoma and nodal marginal zone lymphoma], mantle cell lymphoma, Waldenström’s macroglobulinaemia or other types of lymphoplasmacytic lymphoma).
- You have had at least one previous course of treatment.
- Your lymphoma has relapsed or got worse since your last treatment.
- Your lymphoma has CD20 protein, even if it hasn’t responded to previous treatment with rituximab.
- Your lymphoma is measurable with the imaging tests used in the trial.
- You have at least one area of lymphoma that is easy to biopsy.
- You are well enough to look after yourself and are up and about at least 50% of the day even if you are unable to work.
- Your blood and other health test results are satisfactory to meet the requirements of the trial.
- You are willing to use highly effective contraception during the trial and for at least 12 months after your last dose of trial treatment if there is any chance of you or your partner becoming pregnant.
- You are 16 or over.
You will not be able to enter if:
- You have chronic lymphocytic leukaemia or small lymphocytic lymphoma.
- Your lymphoma is in your central nervous system (CNS; brain and spinal cord) unless it was previously in your CNS and is now in remission (no evidence of lymphoma).
- You’ve had another cancer in the last 2 years except certain localised cancers.
- You have had another anti-cancer treatment or immunosuppressive drugs (drugs that dampen the immune system) in the last month or a dose of steroids above 10 mg prednisolone (or equivalent) in the last 2 weeks.
- You have any health problems that your doctor thinks make it unsafe for you to take part in the trial.
- You have an autoimmune disease or an infection that requires systemic (whole-body) treatment.
- You have significant heart problems.
- You have had radiotherapy in the last 2–4 weeks depending how much of your body was treated with radiotherapy.
- You have not recovered from significant side effects from a previous treatment.
- You have had an autologous stem cell transplant in the last 100 days. Note that if you had an autologous stem cell transplant more than 6 months ago, you might be able to enter the trial if your blood counts have recovered completely.
- You have ever had an allogeneic stem cell transplant.
- You have HIV, hepatitis B or hepatitis C.
- You are pregnant or breastfeeding.
- You are allergic to rituximab or any of its ingredients.
More information about this trial is available at clinicaltrials.gov.