Phase 1 study of pomalidomide in children with recurrent, refractory, and progressive central nervous system tumors: A Pediatric Brain Tumor Consortium trial Journal Article


Authors: Fangusaro, J.; Mitchell, D. A.; Kocak, M.; Robinson, G. W.; Baxter, P. A.; Hwang, E. I.; Huang, J.; Onar-Thomas, A.; Dunkel, I. J.; Fouladi, M.; Warren, K. E.
Article Title: Phase 1 study of pomalidomide in children with recurrent, refractory, and progressive central nervous system tumors: A Pediatric Brain Tumor Consortium trial
Abstract: Background: Central nervous system (CNS) malignancies are the most common solid tumors among children, and novel therapies are needed to help improve survival. Pomalidomide is an immunomodulatory agent that displays antiangiogenic and cytotoxic activity, making it an appropriate candidate to explore in pediatric CNS tumors. Methods: A phase 1 first in pediatric trial of pomalidomide was conducted in children with recurrent, progressive, and refractory CNS tumors. The primary objective was to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) when given orally once daily for 21 consecutive days of a 28-day cycle. Once the MTD was established, 12 additional patients were enrolled on expansion cohorts based on age and steroid use. Results: Twenty-nine children were enrolled and 25 were evaluable for dose-limiting toxicity (DLT). The MTD was 2.6 mg/m2 (dose level 2). Four DLTs were observed in three patients at dose level 3 (3.4 mg/m2) includeding grade 3 diarrhea, grade 3 thrombocytopenia, grade 3 lung infection, and grade 4 neutropenia. The most common adverse events were grade 1 and 2 myelosuppression. One patient with an oligodendroglioma had stable disease for nine cycles, and a second patient with an anaplastic pleomorphic xanthoastrocytoma achieved a sustained partial response. Immunologic analyses suggested that pomalidomide triggers immunomodulation. Conclusions: The MTD of pomalidomide is 2.6 mg/m2. It was well tolerated, and immune correlates showed a serum immune response. These data led to an industry-sponsored phase 2 trial of pomalidomide monotherapy in children with recurrent brain tumors (NCT03257631). © 2020 Wiley Periodicals LLC
Keywords: brain tumor; central nervous system tumor; pediatric; pomalidomide; imid agent
Journal Title: Pediatric Blood and Cancer
Volume: 68
Issue: 2
ISSN: 1545-5009
Publisher: Wiley Periodicals, Inc  
Date Published: 2021-02-01
Start Page: e28756
Language: English
DOI: 10.1002/pbc.28756
PUBMED: 33025730
PROVIDER: scopus
PMCID: PMC7757731
DOI/URL:
Notes: Article -- Export Date: 4 January 2021 -- Source: Scopus
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  1. Ira J Dunkel
    324 Dunkel