RiVa
Research type
Research Study
Full title
A phase IIa study of Rituximab and Varlilumab in relapsed or refractory B-cell malignancies
IRAS ID
223132
Contact name
Sean Lim
Contact email
Sponsor organisation
University Hospital Southampton Foundation Trust
Eudract number
2017-000302-37
Duration of Study in the UK
2 years, 8 months, 25 days
Research summary
Research Summary:
Each year, 12,000 people in the UK are diagnosed with B-cell malignancies. B-cell cancers can be divided into high grade or low grade based on how quickly the cancer grows. \nAlthough high grade lymphomas (e.g. diffuse large B-cell lymphoma (DLBCL)) are potentially curable, approximately 30% of patients will relapse after frontline therapy. There is no established standard for second line therapy but consolidation therapy with autologous stem cell transplant is undertaken if a patient is fit enough. Even with transplantation, only 50% of patients will achieve durable remissions. Thus the great majority of patients with relapsed DLBCL will eventually succumb to the disease. \nWhilst low grade diseases lead a less aggressive course, successive remissions become increasingly shorter, necessitating different therapies with each relapse. Thus there is a clear clinical need for more novel therapeutic agents in B-cell lymphoma.\nIn this trial, patients with high grade or low grade B-cell lymphoma whose cancer has come back after initial response or has not responded to treatment will be treated with rituximab and varlilumab. \nVarlilumab is an immunostimulatory antibody. It binds to the normal immune cells and enhances their anti-tumour effect.\nRituximab is an antibody that targets the tumour cells directly. It binds to the CD20 molecule that is present on the surface of normal and malignant B-cells and engages the immune effector cells, leading to killing of the tumour cell. \nOur hypothesis is that varlilumab enhances rituximab-mediated killing of tumour cells by increasing the number of immune effector cells.\nPatients will receive 6 cycles of treatment, with administration of rituximab on day 1 of each cycle and of varlilumab on day 2 of cycles 1,3 and 5. Each cycle is 2 weeks long. Patients will be followed up 2 weeks after they complete the trial treatment and then every 2 months for one year.
Summary of Results:
PURPOSE This trial looked at a combination of two drugs. The drugs were rituximab, which is already used to treat people with B-cell lymphoma, and a new drug called varlilumab. The main aims of this trial were to find out how well rituximab and varlilumab worked as a treatment for B-cell lymphoma and to learn about the side effects.
Rituximab is an antibody that can bind to a marker on normal and malignant B-cells. When rituximab binds to malignant B-cells, it reveals the lymphoma cells to the immune system. Varlilumab, another antibody, aims to boost the immune system by binding to cells of the immune system to attack and kill lymphoma cells.PARTICIPANTS
The trial involved people whose lymphoma had come back (relapsed) or continued to grow after at least 1 different type of treatment (refractory). Between January 2018 and December 2020, a total of 27 patients with B-cell lymphoma received treatment as part of the RiVa trial across 6 hospitals in the UK.
There was a temporary pause to entering new participants on to the RiVa trial in March 2020 because of the COVID-19 pandemic. Participants who were already being treated on the trial continued to do so and the number of hospital visits was reduced to lower the risk of getting COVID-19. Entering new participants on to the trial restarted in August 2020.There were two groups (arms) of participants in this trial called Arm A and Arm B. Both groups had rituximab and varlilumab, but each group had varlilumab at a different time. A computer was used to randomly decide which group each participant would be in.
After 6 cycles of treatment, all patients had an imaging scan (PET-CT scan) to assess their disease and were then followed up regularly for observation.RESULTS
The trial aimed to treat 40 participants as part of the trial, but it was only possible to treat 27 participants. This was because it was harder to find people suitable for the trial, in part due to the COVID-19 pandemic. Of the 27 participants treated, it was possible to assess how well rituximab and varlilumab worked in 26 participants. This was because 1 person was found to have another type of cancer and so could not continue with the trial after their first cycle of treatment.
The study data showed that rituximab and varlilumab possibly helped a small number of people as it was found that the lymphoma:
• went away in 0 people (0%)
• 4 people had a partial response (15%)
• 4 people had a stable response (15%)
• got worse in 18 people (70%)All patients experienced side effects. The most common side effects were constipation, nausea, vomiting, fatigue, reactions related to the treatment, shortness of breath, and rash. Overall, the combination of rituximab and varlilumab was found to be safe.
Some laboratory work looking at the tumour samples collected as part of the trial in more detail is ongoing. This work will give more information on whether rituximab and varlilumab should be studied further in a larger clinical trial.
A more detailed account of the RiVa study and its results will be published in a scientific journal shortly.REC name
South Central - Oxford A Research Ethics Committee
REC reference
17/SC/0317
Date of REC Opinion
30 Aug 2017
REC opinion
Further Information Favourable Opinion