Format

Send to

Choose Destination
Leuk Res. 2014 Mar;38(3):316-22. doi: 10.1016/j.leukres.2013.12.006. Epub 2013 Dec 11.

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

Author information

1
The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: sverstov@mdanderson.org.
2
The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
3
Dana-Farber Cancer Institute, Boston, MA, USA.
4
H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
5
University of California, San Francisco (UCSF), San Francisco, CA, USA.
6
Exelixis, Inc., South San Francisco, CA, USA.

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.

KEYWORDS:

Inhibitor; JAK2; Mutation; Myelofibrosis; XL019

PMID:
24374145
PMCID:
PMC4414320
DOI:
10.1016/j.leukres.2013.12.006
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center