EPT-16A PHASE 1 TRIAL OF LENALIDOMIDE PLUS RADIOTHERAPY IN CHILDREN WITH NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMAS OR HIGH-GRADE GLIOMAS

Abstract

Background: Lenalidomide, a potent thalidomide analog with immunomodulatory effects, is tolerated at higher doses in children (116 mg/m2/d) compared to adults (= 50 mg/m2/d) despite similar pharmacokinetic profiles. In adults with glioblastoma, the maximum tolerated dose of lenalidomide combined with radiation was 15 mg/m2/d (Drappatz 2009). A Phase I study of lenalidomide with concurrent radiation therapy was performed in children with newly diagnosed DIPG or high‐grade glioma to determine the toxicity profile and recommended Phase 2 dose (RP2D). Methods: Eligibility criteria included age, 22 years of age, newly diagnosed, performance score = 60, able to swallow capsules. The dose‐finding period was defined as the Radiation Phase (6 weeks of standard radiation followed by a 2‐week break). Patients received lenalidomide daily throughout radiation therapy at escalating doses. After the 2‐week rest period, patients received Maintenance lenalidomide (116 mg/m2/d x 21 days/28‐day cycle). Results: Twenty‐nine patients enrolled; 24 are evaluable for dose‐finding. (Dose level 32 mg/m2/d, n = 3; 52 mg/m2/d, n = 3; 88 mg/m2/d, n = 8; 116 mg/m2/d, n = 10 including 5 patients <12 yrs, 5 pts > 12 yrs). Demographics: median age 9 yrs (range 4‐19), diagnoses DIPG (n = 13), highgrade glioma (n = 11). Four dose‐limiting toxicities occurred during the dosefinding period: bone marrow failure (116 mg/m2, n = 1) and myelosuppression (88 mg/m2/d, n = 2; 116 mg/m2, n = 1). The MTD was not exceeded. Number of cycles per patient received to date = 1‐28+. Conclusion: Lenalidomide at doses of 116 mg/m2/d, administered daily during radiation therapy, is tolerable and is the RP2D.