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Clinical Trial Summary

Background: People with primary diffuse large B-cell lymphoma of the central nervous system (CNS) and aggressive B-cell lymphomas with secondary CNS involvement have a poor prognosis. Researchers want to learn if a combination of drugs can help. Objective: To learn if it is safe to give people with these cancers VIPOR-Nivo. Eligibility: People aged 18 and older with B-cell lymphoma in the CNS that does not respond to treatment, response to treatment does not last long, or there is no standard treatment. Design: Participants will be screened with: Health history Physical exam Blood, urine, and heart tests CT, PDG PET, and MRI scans. Participants will lie in scanners that take pictures of the body. For some scans, a contrast or chemical agent will be injected into a vein. Lumbar puncture or Ommaya tap. Participants will have a small needle inserted into their lower back or scalp to obtain fluid. Possible tumor biopsy. Participants will have a needle inserted into a tumor to take a sample. Participants will get the study drugs in 21-day cycles. They may have up to 6 treatment cycles. They will take some drugs by infusion into a vein and some drugs by mouth. Participants will get counseling at least every 28 days on the risks of lenalidomide. Participants will have visits throughout the study. Visits may include repeats of the screening tests. They may also include: Bone marrow biopsy. Participants will have a needle inserted into their hipbone to remove marrow. Saliva samples and cheek swabs Participants will have periodic follow-up visits for about 10 years.

Clinical Trial Description

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 (Registered Trademark)]) 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 ;

Study Design

Related Conditions & MeSH terms

NCT number NCT05211336
Study type Interventional
Source National Institutes of Health Clinical Center (CC)
Contact NCI Medical Oncology Referral Office
Phone (240) 760-6050
Email [email protected]
Status Recruiting
Phase Phase 1
Start date April 19, 2022
Completion date June 30, 2028