Phase 1 Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid With Nivolumab (VIPOR-Nivo) for Diffuse Large B-cell Lymphoma Involving the Central Nervous System

• Status: Not yet recruiting
• Trial end date: 2028-06-30

Summary

Background:

• Primary diffuse large B-cell lymphoma of the CNS (PCNSL) and aggressive B-cell lymphomas with secondary CNS involvement (SCNSL) have a poor prognosis

• Most CNS lymphomas (CNSL) exhibit molecular biology features of activated B cell diffuse large B-cell lymphoma (ABC DLBCL)

• We developed VIPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide [Revlimid ]) treatment in systemic lymphomas as a platform most effective for ABC DLBCL

• CNSL often have copy number alterations or chromosomal rearrangements involving the PD-1 ligands, PD-L1 and PD-L2, making this a rational therapeutic target for CNSL

• PD-1 inhibitors have limited monotherapy activity in CNSL, but demonstrate synergy with Bruton s tyrosine kinase (BTK) inhibitors, BCL2 inhibitors, and lenalidomide in pre- clinical models

• All agents in the VIPOR combination achieve meaningful CNS penetration and PD-1 inhibitors have known clinical activity for lymphomas involving the CNS

Objective:

-To determine the safety and tolerability of VIPOR-Nivo in participants with PCNSL and SCNSL

Eligibility:

• Primary diffuse large B-cell lymphoma of the CNS (PCNSL) or an aggressive B-cell lymphoma with secondary involvement of the CNS (SCNSL)

• Relapsed/refractory after prior therapy or ineligible for standard frontline therapy

• Age >= 18 years

• No pregnant women

• Adequate organ function

Study Design:

• A safety study of 10 evaluable participants with PCNSL or SCNSL (accrual ceiling will be set at 12 to allow for inevaluable participants or screen failures)

• Participants will first be treated with a 21-day Window of lenalidomide and nivolumab to identify early signs of clinical activity with the doublet

• Participants will then receive VIPOR-Nivo in 21-day cycles for a maximum of 6 cycles

• Phase: Phase 1

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Lenalidomide; Nivolumab; Obinutuzumab; Prednisone; Venetoclax