29 research outputs found
An Agenda to Advance Research in Myelodysplastic Syndromes: A TOP 10 Priority List From the First International Workshop in MDS
Correspondence Regarding the Consensus Statement from the Worldwide Network for Blood and Marrow Transplantation Standing Committee on Donor Issues
Glucocorticoid receptor expression is associated with inferior overall survival independent of BRCA mutation status in ovarian cancer
Brca1 Deficiency Causes Bone Marrow Failure and Spontaneous Hematologic Malignancies in Mice
Efficacy of Single-Agent Decitabine in Relapsed and Primary Refractory (rel/ref) Acute Myeloid Leukemia (AML)
A phase I study of selinexor in combination with high-dose cytarabine and mitoxantrone for remission induction in patients with acute myeloid leukemia
Abstract Background Novel therapies for patients with acute myeloid leukemia (AML) are imperative, particularly for those with high-risk features. Selinexor, an exportin 1 (XPO1/CRM1) inhibitor, has demonstrated anti-leukemia activity as a single agent, as well as in combination with anthracyclines and/or DNA-damaging agents. Methods We report the findings of a phase I dose escalation trial with cohort expansion in 20 patients with newly diagnosed or relapsed/refractory AML that combined selinexor with age-adjusted high-dose cytarabine and mitoxantrone (HiDAC/Mito). Results Three (15%) patients received the initial dose of 60 mg of selinexor (~ 35 mg/m2), and 17 (85%) received the target level of 80 mg (~ 50 mg/m2). No dose-limiting toxicities were observed. Common adverse events included febrile neutropenia (70%), diarrhea (40%), anorexia (30%), electrolyte abnormalities (30%), bacteremia (25%), cardiac toxicities (25%), fatigue (25%), and nausea/vomiting (25%). None were unexpected given the HiDAC/Mito regimen. Serious adverse events occurred in 6 (30%) patients; one was fatal. Ten (50%) patients achieved a complete remission (CR), 3 (15%) achieved CR with incomplete recovery (CRi), 1 (5%) achieved partial remission (PR), and 6 (30%) had progressive disease for an overall response rate (ORR) of 70%. Eight of 14 (57%) responders proceeded to allogeneic stem cell transplantation. Correlative studies of WT1 levels showed persistently detectable levels in patients who either did not respond or relapsed quickly after induction. Conclusion The selinexor/HiDAC/Mito regimen is feasible and tolerable at selinexor doses of 80 mg/day (~ 50 mg/m2/day) twice weekly. The recommended phase II dose is 80 mg and warrants further study in this combination. Trial registration ClinicalTrials.gov , NCT02573363 . Registered October 5, 201