Myelofibrosis
Conditions
Keywords
Myelofibrosis, Selinexor, Ruxolitinib, Janus kinase 2, Myeloproliferative neoplasms
Brief summary
This is a global, multicenter, 2-part 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 Phase 2 dose (RP2D) 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). Phase 3 (ongoing), double-blind, placebo-controlled part of the study comparing the efficacy and safety of combination therapy of selinexor + ruxolitinib with combination of placebo + ruxolitinib.
Interventions
DRUGSelinexor
Participants will receive a dose of 40 or 60 mg selinexor oral tablets QW.
OTHERPlacebo
Participants will receive a matching placebo of selinexor oral tablets QW
DRUGRuxolitinib
Participants will receive a dose of 15 or 20 mg ruxolitinib oral tablets BID.
Sponsors
Karyopharm Therapeutics Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Phase 1, open-label, selinexor dose escalation and expansion part (enrollment completed). Phase 3, randomized, double-blind, placebo-controlled part.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged ≥ 18 years * A diagnosis of primary MF or post-essential thrombocythemia (ET) or postpolycythemia- vera (PV) MF. * Active symptoms of MF as determined by presence of at least 2 symptoms using the Myelofibrosis Symptom Assessment Form (MFSAF) V4.0. * Participants with international prognostic scoring system (DIPSS) risk category of intermediate-1, or intermediate-2, or high-risk. * Measurable splenomegaly during the screening period as demonstrated by spleen volume of greater than or equal to (\>=) 450 cubic centimeter (cm\^3) . * Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (\<=) 2.
Exclusion criteria
* More than 10% blasts in peripheral blood or bone marrow (accelerated or blast phase). * Previous treatment with JAK inhibitors for MF. * Previous treatment with selinexor or other XPO1 inhibitors.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 3: Proportion of Participants with Spleen Volume Reduction (SVR) of Greater than or Equal to (>=) 35 Percent (%) (SVR35) at Week 24 Measured by the Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) Scan | At Week 24 |
| Phase 3: Absolute mean change in TSS (Abs-TSS) from baseline to Week 24 as measured by the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 | At Week 24 |
| Phase 1: Maximum Tolerated Dose (MTD) | Approximately within the first cycle (28 days) of therapy |
| Phase 1: Recommended Phase 2 Dose (RP2D) | Approximately within the first cycle (28 days) of therapy |
| Phase 1: Number of Participants With Adverse Events (AEs) by Occurrence, Nature, and Severity | From start of drug administration up to 30 days after last dose of study treatment (approximately 48 months) |
Secondary
| Measure | Time frame |
|---|---|
| Phase 3: Overall survival (OS) | From Baseline up to EoS (approximately 48 months) |
| Phase 3: Progression-free survival (PFS) | Time from randomization until disease progression or death, whichever occurs first (approximately 48 months) |
Countries
Australia, Belgium, Bulgaria, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Netherlands, Poland, Romania, South Korea, Spain, Taiwan, United Kingdom, United States
Outcome results
None listed