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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11130/19:10398462

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Pediatric Blood and Cancer

ISSN

1545-5009

e-ISSN

—

Svazek periodika

66

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

e27900

Kód UT WoS článku

000482516500005

EID výsledku v databázi Scopus

2-s2.0-85068612467