Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis

Phase 3

Active, not recruiting

• Conditions: Myelofibrosis
• Interventions: Drug: Selinexor; Other: Placebo; Drug: Ruxolitinib

• Registration Number: NCT04562389
• Lead Sponsor: Karyopharm Therapeutics Inc

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-14
• Study First Submitted QC: 2020-09-18
• Study First Posted: 2020-09-24
• Study Start: 2021-03-11
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-30
• Last Update Posted: 2025-10-03
• Primary Completion: 2026-03
• Study Completion: 2028-03-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 353

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 1a: Cohort 2: Selinexor 60 mg + Ruxolitinib BID	Selinexor	Participants with MF will receive a dose of 60 mg selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.
Phase 3: Placebo + Ruxolitinib BID	Placebo	Participants with MF will receive a matching placebo of selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with a starting dose of 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.
Phase 1a: Cohort 1: Selinexor 40 mg + Ruxolitinib BID	Selinexor	Participants with MF will receive a dose of 40 milligrams (mg) selinexor oral tablets once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib twice a day (BID) based on the participants baseline platelet count.
Phase 1a: Cohort 2: Selinexor 60 mg + Ruxolitinib BID	Ruxolitinib	Participants with MF will receive a dose of 60 mg selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.
Phase 1a: Cohort 1: Selinexor 40 mg + Ruxolitinib BID	Ruxolitinib	Participants with MF will receive a dose of 40 milligrams (mg) selinexor oral tablets once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib twice a day (BID) based on the participants baseline platelet count.
Phase 1b: Selinexor and Ruxolitinib BID	Selinexor	Participants with MF will receive a dose of 40 or 60 mg selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.
Phase 1b: Selinexor and Ruxolitinib BID	Ruxolitinib	Participants with MF will receive a dose of 40 or 60 mg selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.
Phase 3: Selinexor 60 mg + Ruxolitinib BID	Selinexor	Participants with MF will receive a fixed starting dose of 60 mg selinexor (RD) oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with a starting dose of 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.
Phase 3: Selinexor 60 mg + Ruxolitinib BID	Ruxolitinib	Participants with MF will receive a fixed starting dose of 60 mg selinexor (RD) oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with a starting dose of 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.
Phase 3: Placebo + Ruxolitinib BID	Ruxolitinib	Participants with MF will receive a matching placebo of selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with a starting dose of 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)

Trial Locations

Locations (162)

UAB Division of Hematology/Oncology; 🇺🇸 Birmingham, Alabama, United States

UCLA - Satellite Site; 🇺🇸 Encino, California, United States

City of Hope; 🇺🇸 Duarte, California, United States

City of Hope - Irvine Lennar - Satellite; 🇺🇸 Irvine, California, United States

UCLA; 🇺🇸 Los Angles, California, United States

The Oncology Institute of Hope & Innovation; 🇺🇸 Pasadena, California, United States

USOR - Rocky Mountain Cancer Centers - Aurora; 🇺🇸 Aurora, Colorado, United States

Smilow Cancer Hospital - New Haven; 🇺🇸 New Haven, Connecticut, United States

Georgetown Lombardi Comprehensive Center; 🇺🇸 Washington D.C., District of Columbia, United States

Norton Cancer Institute - Saint Matthews; 🇺🇸 Louisville, Kentucky, United States

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