Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia
Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia
复制标题
DOI：
10.1182/blood-2011-07-366930
复制
发表时间：
2011-12-01
期刊：
影响因子：
20.3
通讯作者：
Kantarjian, Hagop
中科院分区：
文献类型：
--
作者：
Lowenberg, Bob;Muus, Petra;Kantarjian, Hagop
这项由两部分组成的1/2期研究的主要目标是确定强效和选择性的Aurora B激酶抑制剂Barasertib(AZD1152)在新诊断或复发的急性髓细胞白血病(AML)患者中的最大耐受量(MTD)。A组测定巴拉司替布每21天连续滴注7天的MTD。在B部分，在MTD评估巴拉瑟布的疗效。A组32例，分别给予巴拉司替布50 mg(n=3)、100 mg(n=3)、200 mg(n=3)、400 mg(n=4)、800 mg(n=7)、1200 mg(n=6)、1600 mg(n=6)。报告了800 mg(n=1)、1200 mg(n=1)和1600 mg(n=2)组的剂量限制性毒性(口腔炎/粘膜炎症事件)。MTD定义为1200 mg。B组：32例患者接受巴拉司替布1200 mg治疗。在研究的每个部分，32名患者中有8名患者的血液学反应符合Cheson AML标准。最常见的3级事件是发热性中性粒细胞减少(n=24)和口腔炎/粘膜炎症(n=16)。我们的结论是，在复发或新诊断的AML患者中，巴拉司替布的MTD为1200 mg。毒性是可控的，巴拉司替布治疗导致总体血液学应答率为25%。这项研究在www.Clinicaltrials.gov上注册为NCT00497991。(血。2011；118(23)：6030-6036)
The primary objective of this 2-part phase 1/2 study was to determine the maximum-tolerated dose (MTD) of the potent and selective Aurora B kinase inhibitor barasertib (AZD1152) in patients with newly diagnosed or relapsed acute myeloid leukemia (AML). Part A determined the MTD of barasertib administered as a continuous 7-day infusion every 21 days. In part B, the efficacy of barasertib was evaluated at the MTD. In part A, 32 patients were treated with barasertib 50 mg (n = 3), 100 mg (n = 3), 200 mg (n = 3), 400 mg (n = 4), 800 mg (n = 7), 1200 mg (n = 6), and 1600 mg (n = 6). Dose-limiting toxicities (stomatitis/mucosal inflammation events) were reported in the 800 mg (n = 1), 1200 mg (n = 1), and 1600 mg (n = 2) groups. The MTD was defined as 1200 mg. In part B, 32 patients received barasertib 1200 mg. In each part of the study, 8 of 32 patients had a hematologic response according to Cheson AML criteria. The most commonly reported grade >= 3 events were febrile neutropenia (n = 24) and stomatitis/mucosal inflammation (n = 16). We concluded that the MTD of barasertib is 1200 mg in patients with relapsed or newly diagnosed AML. Toxicity was manageable and barasertib treatment resulted in an overall hematologic response rate of 25%. This study is registered at www.ClinicalTrials.gov as NCT00497991. (Blood. 2011;118(23):6030-6036)