A phase I trial of lenalidomide and radiotherapy in children with diffuse intrinsic pontine gliomas or high-grade gliomas

Sean J. Hipp*, Stewart Goldman, Aradhana Kaushal, Andra Krauze, Deborah Citrin, John Glod, Kim Walker, Joanna H. Shih, Hema Sethumadhavan, Keith O’Neill, James H. Garvin, Julia Glade-Bender, Matthias A. Karajannis, Mark P. Atlas, Arman Odabas, Louis T. Rodgers, Cody J. Peer, Jason Savage, Kevin A. Camphausen, Roger J. PackerW. Douglas Figg, Katherine E. Warren

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Purpose: This study was performed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of the immunomodulatory agent, lenalidomide, when administered daily during 6 weeks of radiation therapy to children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or high-grade glioma (HGG) Patients & methods: Children and young adults < 22 years of age with newly diagnosed disease and no prior chemotherapy or radiation therapy were eligible. Children with HGG were required to have an inoperable or incompletely resected tumor. Eligible patients received standard radiation therapy to a prescription dose of 54–59.4 Gy, with concurrent administration of lenalidomide daily during radiation therapy in a standard 3 + 3 Phase I dose escalation design. Following completion of radiation therapy, patients had a 2-week break followed by maintenance lenalidomide at 116 mg/m2/day × 21 days of a 28-day cycle. Results: Twenty-nine patients (age range 4–19 years) were enrolled; 24 were evaluable for dose finding (DIPG, n = 13; HGG, n = 11). The MTD was not reached at doses of lenalidomide up to 116 mg/m2/day. Exceptional responses were noted in DIPG and malignant glioma (gliomatosis cerebri) notably at higher dose levels and at higher steady state plasma concentrations. The primary toxicity was myelosuppression. Conclusion: The RP2D of lenalidomide administered daily during radiation therapy is 116 mg/m2/day. Children with malignant gliomas tolerate much higher doses of lenalidomide during radiation therapy compared to adults. This finding is critical as activity was observed primarily at higher dose levels suggesting a dose response.

Original languageEnglish
Pages (from-to)437-445
Number of pages9
JournalJournal of Neuro-Oncology
Issue number3
StatePublished - 1 Sep 2020
Externally publishedYes


  • Diffuse intrinsic pontine glioma
  • High grade glioma
  • Lenalidomide
  • Pediatric neuro-oncology
  • Radiation


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