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Phase I dose-escalation study of volasertib in pediatric patients with acute leukemia or advanced solid tumors

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F19%3A10398462" target="_blank" >RIV/00064203:_____/19:10398462 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216208:11130/19:10398462

  • Result on the web

    <a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=0J0qP3p_mH" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=0J0qP3p_mH</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1002/pbc.27900" target="_blank" >10.1002/pbc.27900</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Phase I dose-escalation study of volasertib in pediatric patients with acute leukemia or advanced solid tumors

  • Original language description

    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 &lt;18 years with relapsed/refractory acute leukemia/advanced solid tumors (ST) without available effective treatments were enrolled-cohort C1 (aged 2 to &lt;12 years); cohort C2 (aged 12 to &lt;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.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30204 - Oncology

Result continuities

  • Project

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2019

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Pediatric Blood and Cancer

  • ISSN

    1545-5009

  • e-ISSN

  • Volume of the periodical

    66

  • Issue of the periodical within the volume

    10

  • Country of publishing house

    US - UNITED STATES

  • Number of pages

    10

  • Pages from-to

    e27900

  • UT code for WoS article

    000482516500005

  • EID of the result in the Scopus database

    2-s2.0-85068612467