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Phase I dose‐escalation study of volasertib in pediatric patients with acute leukemia or advanced solid tumors
Author(s) -
Doz François,
Locatelli Franco,
Baruchel André,
Blin Nicolas,
De Moerloose Barbara,
Frappaz Didier,
Dworzak Michael,
Fischer Matthias,
Stary Jan,
Fuertig Rene,
Riemann Kathrin,
Taube Tillmann,
Reinhardt Dirk
Publication year - 2019
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.27900
Subject(s) - medicine , neutropenia , febrile neutropenia , clinical endpoint , adverse effect , refractory (planetary science) , cohort , oncology , leukemia , clinical trial , chemotherapy , physics , astrobiology
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.