A randomized, open‐label, phase I/II trial to investigate the maximum tolerated dose of the Polo‐like kinase inhibitor BI 2536 in elderly patients with refractory/relapsed acute myeloid leukaemia. (16th August 2013)

• Record Type: Journal Article
• Authors: Müller‐Tidow, Carsten; Bug, Gesine; Lübbert, Michael; Krämer, Alwin; Krauter, Jürgen; Valent, Peter; Nachbaur, David; Berdel, Wolfgang E.; Ottmann, Oliver G.; Fritsch, Holger; Munzert, Gerd; Garin‐Chesa, Pilar; Fleischer, Frank; Taube, Tillmann; Döhner, Hartmut
• Is Part Of: British journal of haematology. Volume 163:Number 2(2013:Oct.)
• Page Start: 214
• Page End: 222
• Publication Date: 2013-08-16
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.12518
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh12518-abs-0001"> <title>Summary</title> <p>Polo‐like kinases (Plks) play an important role in cell cycle checkpoint controls and are over‐expressed in acute myeloid leukaemia (AML). BI 2536, a novel Plk inhibitor, induces mitotic arrest and apoptosis. In this phase I/II trial of BI 2536 in 68 elderly patients with relapsed/refractory AML, three schedules were investigated (day 1, days 1–3, and days 1 + 8). Maximum tolerated dose was 350 and 200 mg in the day 1 and days 1 + 8 schedules, respectively. The day 1–3 schedule appeared equivalent to the day 1 schedule and was discontinued early. BI 2536 exhibited multi‐compartmental pharmacokinetic behaviour. The majority of patients showed an increase of bone marrow cells in G2/M with a characteristic pattern of mitotic catastrophe. The overall response rate in the day 1 and day 1 + 8 schedules was 9% (5/54) with 2 complete and 3 partial responses. The majority of drug‐related adverse events grade ≥3 were haematological. Taken together, Plk inhibition induced cell cycle arrest in AML blasts <italic>in vivo</italic> and BI 2536 monotherapy showed modest clinical activity in this poor prognosis patient group.</p> </abstract>