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

doi:10.1016/j.leukres.2013.12.006

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 journal › Article › peer-review

44 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 language	English (US)
Pages (from-to)	316-322
Number of pages	7
Journal	Leukemia Research
Volume	38
Issue number	3
DOIs	https://doi.org/10.1016/j.leukres.2013.12.006
State	Published - Mar 2014
Externally published	Yes

Keywords

Inhibitor
JAK2
Mutation
Myelofibrosis
XL019

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.leukres.2013.12.006

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@article{081c3e9b0e144bc08c92d802137021cd,

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

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",

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

note = "Funding Information: 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. Funding Information: This work was supported by funding from the Leukemia & Lymphoma Society (to CCS and NPS), by the UCSF T-32 Molecular Mechanisms of Cancer grant (to CCS) and by Art and Alison Kern. We thank Leo Tseng and Linh Nguyen for the pharmacokinetic data. ",

year = "2014",

month = mar,

doi = "10.1016/j.leukres.2013.12.006",

language = "English (US)",

volume = "38",

pages = "316--322",

journal = "Leukemia Research",

issn = "0145-2126",

publisher = "Elsevier Limited",

number = "3",

}

TY - JOUR

T1 - Phase I evaluation of XL019, an oral, potent, and selective JAK2 inhibitor

AU - Verstovsek, Srdan

AU - Tam, Constantine S.

AU - Wadleigh, Martha

AU - Sokol, Lubomir

AU - Smith, Catherine C.

AU - Bui, Lynne A.

AU - Song, Chunyan

AU - Clary, Douglas O.

AU - Olszynski, Patrycja

AU - Cortes, Jorge

AU - Kantarjian, Hagop

AU - Shah, Neil P.

N1 - Funding Information: 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. Funding Information: This work was supported by funding from the Leukemia & Lymphoma Society (to CCS and NPS), by the UCSF T-32 Molecular Mechanisms of Cancer grant (to CCS) and by Art and Alison Kern. We thank Leo Tseng and Linh Nguyen for the pharmacokinetic data.

PY - 2014/3

Y1 - 2014/3

N2 - 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.

AB - 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.

KW - Inhibitor

KW - JAK2

KW - Mutation

KW - Myelofibrosis

KW - XL019

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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