Universität zu Köln

Doz, Francois, Locatelli, Franco, Baruchel, Andre, Blin, Nicolas, De Moerloose, Barbara ORCID: 0000-0002-2449-539X, Frappaz, Didier ORCID: 0000-0002-3684-9909, Dworzak, Michael, Fischer, Matthias, Stary, Jan, Fuertig, Rene, Riemann, Kathrin, Taube, Tillmann ORCID: 0000-0001-8990-576X and Reinhardt, Dirk (2019). Phase I dose-escalation study of volasertib in pediatric patients with acute leukemia or advanced solid tumors. Pediatr. Blood Cancer, 66 (10). HOBOKEN: WILEY. ISSN 1545-5017

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Abstract

Background Volasertib induces mitotic arrest and apoptosis by targeting Polo-like kinases. In this phase I dose-escalation study, the maximum tolerated dose (MTD), pharmacokinetics (PK), and preliminary efficacy of volasertib were determined in pediatric patients. Methods Patients aged 2 to <18 years with relapsed/refractory acute leukemia/advanced solid tumors (ST) without available effective treatments were enrolled-cohort C1 (aged 2 to <12 years); cohort C2 (aged 12 to <18 years). The patients received volasertib intravenously (starting dose: 200 mg/m(2) body surface area on day 1, every 14 days). The primary endpoint was the pediatric MTD for further development. Results Twenty-two patients received treatment (C1: leukemia, n = 4; ST, n = 8; C2: leukemia, n = 3; ST, n = 7). No dose-limiting toxicities (DLTs) occurred up to 300 mg/m(2) volasertib in C1; two patients in C2, at 250 mg/m(2) volasertib, had DLTs in cycle 1, one of which led to death; therefore, the MTD of volasertib in C2 was 200 mg/m(2). The most common grade 3/4 adverse events (all patients) were febrile neutropenia, thrombocytopenia, and neutropenia (41% each). Stable disease (SD) was the best objective response (leukemia, n = 5; ST, n = 2); the duration of SD was short in all patients, except in one with an ST. PK profiles were generally comparable across dose groups and were consistent with those in adults. Conclusion The pediatric MTD/dose for further development was identified. There were no unexpected safety or PK findings; limited antitumor/antileukemic activity was demonstrated.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Doz, Francois UNSPECIFIED UNSPECIFIED UNSPECIFIED Locatelli, Franco UNSPECIFIED UNSPECIFIED UNSPECIFIED Baruchel, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED Blin, Nicolas UNSPECIFIED UNSPECIFIED UNSPECIFIED De Moerloose, Barbara UNSPECIFIED orcid.org/0000-0002-2449-539X UNSPECIFIED Frappaz, Didier UNSPECIFIED orcid.org/0000-0002-3684-9909 UNSPECIFIED Dworzak, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Stary, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuertig, Rene UNSPECIFIED UNSPECIFIED UNSPECIFIED Riemann, Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Taube, Tillmann UNSPECIFIED orcid.org/0000-0001-8990-576X UNSPECIFIED Reinhardt, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-133400
DOI:	10.1002/pbc.27900
Journal or Publication Title:	Pediatr. Blood Cancer
Volume:	66
Number:	10
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1545-5017
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language KINASE INHIBITOR VOLASERTIB; ACUTE MYELOID-LEUKEMIA; BI 6727; ANTITUMOR-ACTIVITY; OPEN-LABEL; CANCER; TRIAL; CELLS; PLK1; ADOLESCENTS Multiple languages Oncology; Hematology; Pediatrics Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13340