| Literature DB >> 31545113 |
Bhavana Bhatnagar1,2, Qiuhong Zhao1,2, Alice S Mims1,2, Sumithira Vasu1,2, Gregory K Behbehani1,2, Karilyn Larkin1,2, James S Blachly1,2, William Blum3, Rebecca B Klisovic3, Amy S Ruppert1,2, Shelley Orwick2, Christopher Oakes1, Parvathi Ranganathan1,2, John C Byrd1,2, Alison R Walker1,2, Ramiro Garzon1,2.
Abstract
Current treatment options for older and relapsed or refractory (R/R) acute myeloid leukemia (AML) patients are limited and represent an unmet need. Based on preclinical studies showing strong anti-leukemic effects in vivo, this phase I dose-escalation study assessed the safety and preliminary clinical activity of the oral exportin-1 inhibitor, selinexor, in combination with the hypomethylating agent, decitabine 20 mg/m2, in adults with R/R AML and in older (age ≥ 60) untreated AML patients. There were no protocol-defined dose limiting toxicities. The recommended phase 2 dose of selinexor was 60 mg (∼35 mg/m2) given twice-weekly. Notable grade ≥3 toxicities included asymptomatic hyponatremia (68%), febrile neutropenia (44%), sepsis (44%), hypophosphatemia (36%), and pneumonia (28%). In 25 patients, the overall response rate was 40%. Modification of selinexor to a flat dose of 60 mg, twice-weekly for two weeks after decitabine, improved tolerability of the regimen and demonstrated preliminary clinical activity in poor-risk patients with AML.Entities:
Keywords: Acute myeloid leukemia; clinical trials; decitabine; selinexor
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Year: 2019 PMID： 31545113 PMCID： PMC7552944 DOI： 10.1080/10428194.2019.1665664
Source DB: PubMed Journal: Leuk Lymphoma ISSN： 1026-8022