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Ref Type Journal Article
PMID (24374145)
Authors Verstovsek S, Tam CS, Wadleigh M, Sokol L, Smith CC, Bui LA, Song C, Clary DO, Olszynski P, Cortes J, Kantarjian H, Shah NP
Title Phase I evaluation of XL019, an oral, potent, and selective JAK2 inhibitor.
Journal Vol Issue Date Pages Journal Short Title
Leukemia research 38 3 2014 Mar 316-22 Leuk Res
URL
Abstract Text 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
XL019 XL019 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
XL019 JAK2 Inhibitor - ATP competitive 15 XL019 is a selective ATP-competitive JAK2 inhibitor, which reduces downstream STAT activation and may reduce tumor growth (PMID: 23127890, PMID: 24374145, PMID: 30243158).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References