Abstract 648TiP
Background
CNS relapse in patients with Diffuse Large B Cell Lymphoma (DLBCL) is usually an early complication and with poor prognosis. R-CHOP, the standard treatment for DLBCL plays a minimal role preventing leptomeningeal and/or brain parenchyma relapse. Risk factors have been previously identified for this complication and high dose intravenous methotrexate (HDMTX) has been suggested as an effective strategy to prevent CNS lymphoma relapse (GELTAMO guidelines Haematologica 2017 and British guidelines BJAEM 2020). Unfortunately the administration of HDMTX is related with risk of renal, hepatic and haematological adverse events.
Trial design
Methods: This is an open-label, interventional, non-randomized, phase 2, pilot, multicenter study in Diffuse large B-cell lymphoma (DLBCL) patients at high risk of CNS relapse to assess of prophylactic effect of 2,000 unit of Glucarpidase in MTX related-toxicity administered after 12 hours of HDMTX. This study will be performed in the context of in-patients setting for receiving the three HDMTX courses. Criteria for CNS involvement are concordant with those of the last approved version of the GELTAMO guideline for the diagnostic, prevention, and therapeutical management of Central Nervous System involvement in patients with diffuse large cell B Lymphoma (revised 2017) [1]. Inclusion criteria: Age 18 year and above, diagnosis with diffuse large B-cell lymphoma at high risk of CNS involvement and adequate haematological, renal and hepatic function. Criteria to consider risk of CNS involvement were: >=2 extranodal site involved plus an elevated LDH and/or lymphoma involvement of the testis, breast, adrenal gland or kidney In order to include patients without CNS involvement, patients will be included in the study with a negative result of the CSF cytometry flow test, which will be performed according to normal clinical practice. Primary objective is: To describe the reduction of MTX levels after systematic administration of reduced Glucarpidase doses (2,000 units) 12 hours following start of HDMTX infusion in DLBCL patients at high risk for CNS involvement, receiving multiple cycles of HDMTX. Secondary objectives are: To analyze the prophylactic effect of Glucarpidase administered after 12 hour of high-dose MTX (HDMTX) on the incidence and severity and duration of MTX related-toxicity (renal toxicity, mucositis, liver toxicity, neutropaenia, thrombocytopaenia). To assess the incidence of CNS relapse during one year To assess the length of hospital stay (LOS) during HDMTX therapy To analyze the appearance of antibodies against Glucarpidase To analyze the appearance of neutralizing antibodies against Glucarpidase The study is currently enrolling.
Clinical trial identification
NCT05022797.
Editorial acknowledgement
Legal entity responsible for the study
CRIS Fundation.
Funding
BTG.
Disclosure
All authors have declared no conflicts of interest.