Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis

Phase 3Active Not RecruitingNCT04562389

Karyopharm Therapeutics Inc353 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

353

Conditions

Myelofibrosis

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (166)

UAB Division of Hematology/Oncology

Birmingham, Alabama, United States

UCLA - Satellite Site

Beverly Hills, California, United States

City of Hope

Duarte, California, United States

UCLA - Satellite Site

Encino, California, United States

City of Hope - Irvine Lennar - Satellite

Irvine, California, United States

Outcomes

Primary Outcomes

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

Time frame: 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

Time frame: At Week 24

Phase 1: Maximum Tolerated Dose (MTD)

Time frame: Approximately within the first cycle (28 days) of therapy

Phase 1: Recommended Phase 2 Dose (RP2D)

Time frame: Approximately within the first cycle (28 days) of therapy

Phase 1: Number of Participants With Adverse Events (AEs) by Occurrence, Nature, and Severity

Time frame: From start of drug administration up to 30 days after last dose of study treatment (approximately 48 months)

Secondary Outcomes

Phase 3: Overall survival (OS)

Time frame: From Baseline up to EoS (approximately 48 months)

Phase 3: Progression-free survival (PFS)

Time frame: Time from randomization until disease progression or death, whichever occurs first (approximately 48 months)