A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies

Carlos Graux; Anne Sonet; Johan Maertens; Justus Duyster; Jochen Greiner; Yves Chalandon; Giovanni Martinelli; Dagmar Hess; Dominik Heim; Francis J. Giles; Kevin R. Kelly; Athos Gianella-Borradori; Blandine Longerey; Ekaterine Asatiani; Narmyn Rejeb; Oliver G. Ottmann

doi:10.13025/25043

A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies

Carlos Graux
, Anne Sonet
, Johan Maertens
, Justus Duyster
, Jochen Greiner
, Yves Chalandon
, Giovanni Martinelli
, Dagmar Hess
, Dominik Heim
, Francis J. Giles
, Kevin R. Kelly
, Athos Gianella-Borradori
, Blandine Longerey
, Ekaterine Asatiani
, Narmyn Rejeb
, Oliver G. Ottmann

Clinique Universitaire de Mont-Godinne
KU Leuven– University Hospital Leuven
Technical University Munich
Albert Ludwigs University
Ulm University
Geneva University Hospitals
University of Bologna
Cantonal Hospital St. Gallen
University Hospital Basel
HRB Clinical Research Facility
University of Texas Health Science Center San Antonio
Merck Serono S.A.
Clavis Pharma
Goethe University

Research output: Contribution to a Journal (Peer & Non Peer) › Article › peer-review

19 Citations (Scopus)

Abstract

A phase I dose-escalation study of MSC1992371A, an oral aurora kinase inhibitor, was carried out in patients with hematologic malignancies. Patients received escalating doses either on days 1-3 and 8-10 (n=36) or on days 1-6 (n=39) of a 21-day cycle. The maximum tolerated doses were 37 and 28mg/m²/day, respectively. Dose-limiting toxicities included severe neutropenia with infection and sepsis, mucositis/stomatitis, and diarrhea. Complete responses occurred in 3 patients. Four disease-specific expansion cohorts then received the dose and schedule dictated by the escalation phase but the study was prematurely discontinued due to hematologic and gastrointestinal toxicity at clinically effective doses.

Original language	English
Pages (from-to)	1100-1106
Number of pages	7
Journal	Leukemia Research
Volume	37
Issue number	9
DOIs	https://doi.org/10.13025/25043 https://doi.org/10.1016/j.leukres.2013.04.025
Publication status	Published - Sept 2013
Externally published	Yes

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Aurora kinase inhibitor
Hematologic malignancies
MSC1992371A
Phase l

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10.13025/25043Licence: CC BY-NC-ND
10.1016/j.leukres.2013.04.025

Cite this

Graux, C., Sonet, A., Maertens, J., Duyster, J., Greiner, J., Chalandon, Y., Martinelli, G., Hess, D., Heim, D., Giles, F. J., Kelly, K. R., Gianella-Borradori, A., Longerey, B., Asatiani, E., Rejeb, N., & Ottmann, O. G. (2013). A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies. Leukemia Research, 37(9), 1100-1106. https://doi.org/10.13025/25043, https://doi.org/10.1016/j.leukres.2013.04.025

@article{5018e9655a584ef5b62d726800823e13,

title = "A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies",

abstract = "A phase I dose-escalation study of MSC1992371A, an oral aurora kinase inhibitor, was carried out in patients with hematologic malignancies. Patients received escalating doses either on days 1-3 and 8-10 (n=36) or on days 1-6 (n=39) of a 21-day cycle. The maximum tolerated doses were 37 and 28mg/m2/day, respectively. Dose-limiting toxicities included severe neutropenia with infection and sepsis, mucositis/stomatitis, and diarrhea. Complete responses occurred in 3 patients. Four disease-specific expansion cohorts then received the dose and schedule dictated by the escalation phase but the study was prematurely discontinued due to hematologic and gastrointestinal toxicity at clinically effective doses.",

keywords = "Aurora kinase inhibitor, Hematologic malignancies, MSC1992371A, Phase l",

author = "Carlos Graux and Anne Sonet and Johan Maertens and Justus Duyster and Jochen Greiner and Yves Chalandon and Giovanni Martinelli and Dagmar Hess and Dominik Heim and Giles, \{Francis J.\} and Kelly, \{Kevin R.\} and Athos Gianella-Borradori and Blandine Longerey and Ekaterine Asatiani and Narmyn Rejeb and Ottmann, \{Oliver G.\}",

year = "2013",

month = sep,

doi = "10.13025/25043",

language = "English",

volume = "37",

pages = "1100--1106",

journal = "Leukemia Research",

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Graux, C, Sonet, A, Maertens, J, Duyster, J, Greiner, J, Chalandon, Y, Martinelli, G, Hess, D, Heim, D, Giles, FJ, Kelly, KR, Gianella-Borradori, A, Longerey, B, Asatiani, E, Rejeb, N & Ottmann, OG 2013, 'A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies', Leukemia Research, vol. 37, no. 9, pp. 1100-1106. https://doi.org/10.13025/25043, https://doi.org/10.1016/j.leukres.2013.04.025

TY - JOUR

T1 - A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies

AU - Graux, Carlos

AU - Sonet, Anne

AU - Maertens, Johan

AU - Duyster, Justus

AU - Greiner, Jochen

AU - Chalandon, Yves

AU - Martinelli, Giovanni

AU - Hess, Dagmar

AU - Heim, Dominik

AU - Giles, Francis J.

AU - Kelly, Kevin R.

AU - Gianella-Borradori, Athos

AU - Longerey, Blandine

AU - Asatiani, Ekaterine

AU - Rejeb, Narmyn

AU - Ottmann, Oliver G.

PY - 2013/9

Y1 - 2013/9

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AB - A phase I dose-escalation study of MSC1992371A, an oral aurora kinase inhibitor, was carried out in patients with hematologic malignancies. Patients received escalating doses either on days 1-3 and 8-10 (n=36) or on days 1-6 (n=39) of a 21-day cycle. The maximum tolerated doses were 37 and 28mg/m2/day, respectively. Dose-limiting toxicities included severe neutropenia with infection and sepsis, mucositis/stomatitis, and diarrhea. Complete responses occurred in 3 patients. Four disease-specific expansion cohorts then received the dose and schedule dictated by the escalation phase but the study was prematurely discontinued due to hematologic and gastrointestinal toxicity at clinically effective doses.

KW - Aurora kinase inhibitor

KW - Hematologic malignancies

KW - MSC1992371A

KW - Phase l

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VL - 37

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JF - Leukemia Research

IS - 9

ER -

A phase I dose-escalation study of MSC1992371A, an oral inhibitor of aurora and other kinases, in advanced hematologic malignancies

Abstract

UN SDGs

Keywords

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