RCHOP Chemoimmunotherapy Preceded BY BBB Permeabilization by t-NGR Necrosis Factor
Status:
Unknown status
Trial end date:
2020-01-27
Target enrollment:
Participant gender:
Summary
Patients with primary central nervous system lymphoma (PCNSL) are treated with
high-dose-methotrexate-based chemotherapy, which requires hospitalization and extensive
expertise to manage related toxicity. Treatment with R-CHOP, the most commonly used
combination against aggressive lymphomas, could overcome these difficulties, but CNS
bioavailability of related drugs is poor due to their limited capability to cross the
blood-brain barrier (BBB). Tumor necrosis factor (TNF) induces selective BBB permeabilization
and enhances CNS access of anticancer drugs in animal models. The addition of NGR peptide
improves biological properties of TNF, resulting in increased drug availability and antitumor
synergistic effect, without increased toxicity. Thus, the addition of NGR-hTNF to R-CHOP may
result in improved CNS drug availability and activity in patients with relapsed/refractory
PCNSL; this hypothesis is being tested in this ongoing phase II trial called "INGRID". This
trial will consider HIV-negative patients (age 18-80 ys; ECOG PS ≤3) with relapsed/refractory
PCNSL previously treated with high-dose-methotrexate-based chemotherapy± radiotherapy, and
with measurable disease.