Cxcr4 Blockade At The End Of Irradiation To Improve Local Control Of Glioblastoma (Gbm).

2019Background: Based on preclinical work identifying an important role for the CXCL12 (SDF1)/CXCR4 chemokine axis in reestablishing vascularity after irradiation of GBM, we launched a Phase I/II study assessing the impact of CXCR4 blockade with a continuous infusion of Plerixafor (AMD3100, Mozobil), an established CXCR4 small molecule antagonist, already in clinical use for bone marrow stem cell mobilization. Methods: Open label Phase I/II study for newly diagnosed adult GBM patients, ages 75 or younger, with KPS of at least 60 were administered a 4-week continuous intravenous infusion starting one week prior to the completion of standard irradiation. Results: 29 patients (median age: 60 years) were enrolled and completed the infusion course. The Phase I study established that 16.6 µg/kg/hr was well tolerated (no Gr III drug associated toxicity) with achievable Plerixafor serum values above the threshold level for CXCR4 blockade. A total of 19 patients underwent DSC-MRI for quantification of relative cer...