A Combination of Rituximab and Varlilumab Immunotherapy in Patients With B-cell Lymphoma — RiVa  

B Cell Lymphoma Clinical Trial

Official title: A Phase IIa Study of RItuximab and VArlilumab in Relapsed or Refractory B-cell Malignancies

Status Active, not recruiting

Clinical Trial Summary

A total of 40 participants will be recruited, with 20 participants in each of the following subcategories:

A) High grade lymphoma (DLBCL, FL grade 3b, transformed FL) (n=20) B) Low grade lymphoma (e.g. FL grade 1, 2 or 3a, MZL, MCL) (n=20)

The main purpose for having two experimental treatment arms is to provide a comparator for the translational endpoints, i.e. to assess whether the differences observed are due to the addition of varlilumab to rituximab. The only difference between Arm A and Arm B is the delay in administration of varlilumab in cycle 1, which is on Day 2 in Arm A and Day 8 in Arm B. As the post-treatment tissue collection occurs on Day 7/8, prior to administration of varlilumab in Arm B, samples will be obtained from participants that have either been treated with rituximab alone, or both rituximab and varlilumab. To minimise any potential risks to the patient as a result of a repeat biopsy on Day 7/8, a prerequisite for entry to the trial is that the participants must have accessible sites for biopsy. Difference in response rates between Arm A and Arm B are not expected.

Clinical Trial Description

A multicentre, randomised, phase IIa study in participants with relapsed or refractory CD20+ B-cell malignancies. The study will be conducted in 2 stages as follows:

Stage 1 - Safety During the safety phase, 6 participants (3 from each Arm and from any subtype) will be treated as detailed in section 6.1. The number of dose limiting toxicities (DLTs) experienced by these participants in each arm after having completed the first cycle will dictate whether the trial will proceed to the second stage.

1. In each arm, if out of these 3 participants 0 experience a DLT, then that arm will proceed to stage 2.

2. In each arm, if out of these 3 participants 1 or 2 experience a DLT, then that arm will be expanded to 3 more participants.

1. If 1 or 2 out of 6 participants experience a dose limiting toxicity, the arm will proceed to Stage 2.

2. If 3 or more out of 6 participants experience a DLT, recruitment for that arm will be stopped.

3. If out of these 3 participants, 3 experience a dose limiting toxicity, recruitment for that arm will be stopped.

Initially, the first patient will be entered into the trial. Providing there are no serious or unexplained safety issues during the first 2 weeks, as determined by the Safety Review Committee (SRC), then dosing of subsequent participants will continue as they are identified. Should toxicity findings of concern occur, the SRC may choose to stagger the start of dosing for subsequent participants and/or cohorts.

The objective of Stage 2 is to obtain some further information on the safety of the intervention in a larger sample, information on activity (response rate overall and per lymphoma subtype) and feasibility of administrating rituximab and varlilumab together. During Stage 2, recruitment will continue so (including those in Stage 1), there is a total of 10 participants per arm and per disease category (a total of 20 participants per disease category, 40 participants in the trial in total). ;

Related Conditions & MeSH terms

• B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell

• NCT number: NCT03307746
• Study type: Interventional
• Source: University Hospital Southampton NHS Foundation Trust
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: November 23, 2017
• Completion date: March 31, 2024