Study of Selinexor in Combination with Ruxolitinib in Myelofibrosis (SENTRY)

Karyopharm Therapeutics

Status and phase: Enrolling; Phase 3

Conditions: Myelofibrosis

Treatments: Drug: Selinexor; Other: Placebo; Drug: Ruxolitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04562389

2023-506139-13-00 (EU Trial (CTIS) Number)

XPORT-MF-034

2020-003883-19 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 350 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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350 participants in 5 patient groups

Phase 1a: Cohort 1: Selinexor 40 mg + Ruxolitinib BID

Experimental group

Description:

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.

Treatment:

Drug: Ruxolitinib

Drug: Selinexor

Drug: Selinexor

Phase 1a: Cohort 2: Selinexor 60 mg + Ruxolitinib BID

Experimental group

Description:

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.

Treatment:

Drug: Ruxolitinib

Drug: Selinexor

Drug: Selinexor

Phase 1b: Selinexor and Ruxolitinib BID

Experimental group

Description:

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.

Treatment:

Drug: Ruxolitinib

Drug: Selinexor

Drug: Selinexor

Phase 3: Selinexor 60 mg + Ruxolitinib BID

Experimental group

Description:

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.

Treatment:

Drug: Ruxolitinib

Drug: Selinexor

Drug: Selinexor

Phase 3: Placebo + Ruxolitinib BID

Active Comparator group

Description:

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.

Treatment:

Drug: Ruxolitinib

Other: Placebo