Journal article
Phase I evaluation of XL019, an oral, potent, and selective JAK2 inhibitor
S Verstovsek, CS Tam, M Wadleigh, L Sokol, CC Smith, LA Bui, C Song, DO Clary, P Olszynski, J Cortes, H Kantarjian, NP Shah
Leukemia Research | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2014
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. © 2013 ..
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Awarded by National Cancer Institute
Funding Acknowledgements
This work was supported by funding from the Leukemia & Lymphoma Society (to CCS and NPS), the UCSF T-32 Molecular Mechanisms of Cancer grant (to CCS), the MD Anderson Cancer Center Support Grant CA016672, and Art and Alison Kern.