Journal
LEUKEMIA & LYMPHOMA
Volume 61, Issue 2, Pages 387-396Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10428194.2019.1665664
Keywords
Acute myeloid leukemia; decitabine; selinexor; clinical trials
Categories
Funding
- Karyopharm Therapeutics
- D. Warren Brown Family Foundation
- [R35 CA197734]
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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/m(2), 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 (similar to 35 mg/m(2)) 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.
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