Phase I evaluation of XL019, an oral, potent, and selective JAK2 inhibitor

Srdan Verstovsek, Constantine S. Tam, Martha Wadleigh, Lubomir Sokol, Catherine C. Smith, Lynne A. Bui, Chunyan Song, Douglas O. Clary, Patrycja Olszynski, Jorge Cortes, Hagop Kantarjian, Neil P. Shah

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

This phase I study evaluated selective JAK2 inhibitor XL019 in 30 patients with myelofibrosis. The initial dose cohorts were 100, 200, and 300. mg orally on days 1-21 of a 28-day cycle. Central and/or peripheral neurotoxicity developed in all patients. Subsequently, patients were treated on lower doses; neurotoxicity was again observed, leading to study termination. Peripheral neuropathy resolved in 50%, and central neurotoxicity in all patients within months after therapy cessation. Myelosuppression was minimal. The terminal half-life of XL019 was approximately 21. h, with steady state reached by Day 8. International Working Group defined responses were seen in three (10%) patients.

Original languageEnglish (US)
Pages (from-to)316-322
Number of pages7
JournalLeukemia Research
Volume38
Issue number3
DOIs
StatePublished - Mar 1 2014
Externally publishedYes

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Keywords

  • Inhibitor
  • JAK2
  • Mutation
  • Myelofibrosis
  • XL019

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Verstovsek, S., Tam, C. S., Wadleigh, M., Sokol, L., Smith, C. C., Bui, L. A., Song, C., Clary, D. O., Olszynski, P., Cortes, J., Kantarjian, H., & Shah, N. P. (2014). Phase I evaluation of XL019, an oral, potent, and selective JAK2 inhibitor. Leukemia Research, 38(3), 316-322. https://doi.org/10.1016/j.leukres.2013.12.006