Study of Selinexor in Combination with Ruxolitinib in Myelofibrosis
Purpose
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.
Condition
- Myelofibrosis
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts 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.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Phase 1, open-label, selinexor dose escalation and expansion part (enrollment completed). Phase 3, randomized, double-blind, placebo-controlled part.
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Phase 1a: Cohort 1: Selinexor 40 mg + Ruxolitinib BID |
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. |
|
|
Experimental Phase 1a: Cohort 2: Selinexor 60 mg + Ruxolitinib BID |
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. |
|
|
Experimental Phase 1b: Selinexor and Ruxolitinib BID |
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. |
|
|
Experimental Phase 3: Selinexor 60 mg + Ruxolitinib BID |
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. |
|
|
Active Comparator Phase 3: Placebo + Ruxolitinib BID |
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. |
|
Recruiting Locations
Vanderbilt Ingram Cancer Center
Nashville, Tennessee 37232
Nashville, Tennessee 37232
More Details
- Status
- Recruiting
- Sponsor
- Karyopharm Therapeutics Inc