Title
A Phase 1/3 Study to Evaluate Efficacy and Safety of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Ruxolitinib in Treatment-Naïve Patients With Myelofibrosis

Description
This is a global, multicenter Phase 1/3 study to evaluate the efficacy and safety of selinexor plus ruxolitinib in JAK inhibitor (JAKi) treatment-naïve myelofibrosis (MF) participants. The study will be conducted in two phases: Phase 1 (open-label) and Phase 3 (double-blind). Phase 1 (enrollment completed) was an open-label evaluation of the safety and recommended dose (RD) of selinexor in combination with ruxolitinib and included a dose escalation using a standard 3+3 design (Phase 1a) and a dose expansion part (Phase 1b). In Phase 3, JAKi treatment-naïve MF participants are enrolled in 2:1 ratio to receive the combination therapy of selinexor + ruxolitinib or the combination of placebo + ruxolitinib.

Objective
Primary
-To evaluate the efficacy of selinexor + ruxolitinib compared to placebo + ruxolitinib in patients with MF

Key Secondary
-To evaluate anemia response in patients with MF receiving selinexor + ruxolitinib compared to placebo + ruxolitinib

Secondary
-To evaluate the survival outcome of patients with MF receiving selinexor + ruxolitinib compared to placebo + ruxolitinib
-To evaluate additional measures of efficacy of selinexor + ruxolitinib compared to placebo + ruxolitinib in patients with MF
-To evaluate the efficacy of selinexor + ruxolitinib in pre-specified MF patient subgroups
-To evaluate the safety of selinexor + ruxolitinib compared to placebo + ruxolitinib in patients with MF
-To characterize pharmacokinetics (PK) of selinexor in patients with MF
-To assess changes in bone marrow fibrosis in patients with MF receiving selinexor + ruxolitinib compared to placebo + ruxolitinib

Treatment Drug: Selinexor
Drug: Selinexor
Other: Placebo
Drug: Ruxolitinib

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Leukemia

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital