Selinexor for Myelofibrosis

(SENTRY-2 Trial)

Recruiting at 56 trial locations

Overseen By Karyopharm Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Karyopharm Therapeutics Inc

Disqualifiers: Pregnancy, Heart disease, Stroke, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Until progression or intolerable toxicity

118 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies a treatment called selinexor for individuals with myelofibrosis, a condition where scar tissue replaces bone marrow, causing issues like an enlarged spleen and low blood cell counts. The trial aims to assess selinexor's effectiveness in reducing spleen size and managing symptoms. It offers different doses of selinexor and may include add-on medications if necessary. This trial might suit individuals with myelofibrosis who have noticeable spleen enlargement and have not previously used JAK inhibitors. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that selinexor has been tested for safety in people with myelofibrosis. One study used selinexor with ruxolitinib in patients not previously treated with JAK inhibitors, a type of medication for blood cancers. The safety data from this study suggested that selinexor is generally well-tolerated, with nausea and fatigue as the most common, manageable side effects.

Another study found that selinexor works better when combined with drugs like corticosteroids and proteasome inhibitors, particularly in patients who have relapsed or are not responding to other treatments. This indicates that selinexor can be safely combined with other medications, which is promising for its overall safety.

While these studies examined different drug combinations and situations, the findings support the idea that selinexor is generally safe for use in humans, though it can have side effects like any medication. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about selinexor for treating myelofibrosis because it offers a different approach compared to standard treatments like ruxolitinib, fedratinib, and momelotinib. Unlike these standard therapies, which primarily target the JAK pathway, selinexor works by inhibiting the nuclear export protein XPO1. This unique mechanism may help manage the disease by affecting cancer cell survival and inflammation differently. Additionally, selinexor is taken orally, providing a convenient option for patients who prefer to avoid frequent clinic visits for infusions or injections.

What evidence suggests that this trial's treatments could be effective for myelofibrosis?

Research has shown that selinexor may help treat myelofibrosis, a type of bone marrow cancer. In this trial, participants will receive either 60 mg or 40 mg of selinexor. One study found that 71% of patients experienced a noticeable decrease in spleen size after 12 weeks, increasing to 79% after 24 weeks. A smaller spleen can lead to fewer symptoms and a better quality of life. Patients taking selinexor also had higher hemoglobin levels, indicating healthier red blood cells, and required fewer blood transfusions. These early results suggest that selinexor could be effective for people with myelofibrosis. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with myelofibrosis who haven't been treated with JAK inhibitors and have moderate thrombocytopenia. They should have symptoms of myelofibrosis, measurable spleen enlargement, specific risk categories per DIPSS, an ECOG Performance Status of 2 or less, certain blood cell counts without transfusions or growth factors recently, and adequate liver function.

Inclusion Criteria

My spleen is enlarged, measuring over 450 cm^3 on a recent scan.

ANC >= 1.0 × 10^9/L without need for growth factors within 7 days prior to the first dose of selinexor

I am willing to fill out a daily symptom diary during the study.

Exclusion Criteria

More than 10% blasts in peripheral blood or bone marrow (accelerated or blast phase)

I have been treated with JAK inhibitors for myelofibrosis.

I can't tolerate two different anti-nausea medications for the first two treatment cycles.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive selinexor 40 mg or 60 mg oral tablets once weekly in 28-day cycles, with optional add-on medication based on spleen volume reduction (SVR) values

Until progression or intolerable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 months

Optional Expansion

Participants may receive additional treatment with selinexor and optional add-on medication based on SVR values

What Are the Treatments Tested in This Trial?

Interventions

• Selinexor

Trial Overview The study tests the effectiveness of Selinexor in reducing spleen volume in patients new to JAK inhibitor treatment for myelofibrosis with low platelet counts. It will compare different doses (40 mg and 60 mg) against other treatments like Pacritinib and Momelotinib.

How Is the Trial Designed?

Group I: Selinexor 60 mg (Optional Expansion Arm) Experimental Treatment 4 Interventions

Participants will receive selinexor 60 mg oral tablets QW (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first. Optional add-on medication (ruxolitinib \[5 mg or 10 mg twice daily\], pacritinib \[200 mg twice daily\], or momelotinib \[200 mg once daily\]) may be initiated for participants whose SVR is less than (\<) 10% at Week 12 or \<35% at Week 24 based on the participants platelet count values (i.e., ruxolitinib if platelets greater than or equal to \[\>=\] 50 x 10\^9/L, pacritinib if platelets \<50 x 10\^9/L, momelotinib if platelets is \>=50 x 10\^9/L and hemoglobin level is \< 10 gram per deciliter \[g/dL\]).

Group II: Selinexor 60 mg (Arm 1) Experimental Treatment 4 Interventions

Participants will receive selinexor 60 milligrams (mg) oral tablets once weekly (QW) (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first and followed by optional add-on medication dosing may be initiated based on Spleen Volume Reduction (SVR) values.

Group III: Selinexor 40 mg (Optional Expansion Arm) Experimental Treatment 4 Interventions

Participants will receive selinexor 40 mg oral tablets QW (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first. Optional add-on medication (ruxolitinib \[5 mg or 10 mg twice daily\], pacritinib \[200 mg twice daily\], or momelotinib \[200 mg once daily\]) may be initiated for participants whose SVR is \<10% at Week 12 or \<35% at Week 24 based on the participants platelet count values (i.e., ruxolitinib if platelets \>= 50 x 10\^9/L, pacritinib if platelets \<50 x 10\^9/L, momelotinib if platelets is \>=50 x 10\^9/L and hemoglobin level is \< 10 g/dL).

Group IV: Selinexor 40 mg (Arm 2) Experimental Treatment 4 Interventions

Participants will receive selinexor 40 mg oral tablets QW (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment, death, or withdrawal of consent, whichever comes first and followed by optional add-on medication dosing may be initiated based on SVR values.

Selinexor is already approved in United States, Canada for the following indications:

Approved in United States as Xpovio for:

• Multiple myeloma
• Diffuse large B-cell lymphoma

Approved in Canada as Xpovio for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Karyopharm Therapeutics Inc

Lead Sponsor

Trials

89

Recruited

7,200+

Richard Paulson

Karyopharm Therapeutics Inc

Chief Executive Officer since 2021

MBA from the University of Toronto's Rotman School of Management

Reshma Rangwala

Karyopharm Therapeutics Inc

Chief Medical Officer since 2023

MD, PhD

Published Research Related to This Trial

CBL0137, a drug derived from curaxin, shows promise in targeting Jak2 mutation-driven myelofibrosis by preferentially affecting CD34+ stem and progenitor cells from patients, indicating its potential as a novel therapy.

In murine models of myeloproliferative neoplasms, CBL0137 effectively reduced splenomegaly and reticulocyte counts, suggesting it may help alleviate some symptoms associated with myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of curaxin as a potential new therapeutic for JAK2 V617F mutant patients. Pearson, S., Blance, R., Yan, F., et al.[2023]

In a phase I study of the selective JAK2 inhibitor XL019 involving 30 patients with myelofibrosis, all participants experienced neurotoxicity, leading to the study's termination after dose adjustments.

Despite the neurotoxicity, which resolved in half of the patients after stopping treatment, myelosuppression was minimal, and only 10% of patients showed defined responses according to International Working Group criteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I evaluation of XL019, an oral, potent, and selective JAK2 inhibitor. Verstovsek, S., Tam, CS., Wadleigh, M., et al.[2021]

Ruxolitinib is an effective treatment for intermediate or high-risk myelofibrosis, significantly reducing spleen size and alleviating related symptoms, which improves patients' quality of life.

While ruxolitinib can cause dose-dependent anemia and thrombocytopenia, these side effects can be managed with dose adjustments and monitoring, allowing most patients to continue treatment without permanent discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing. Mesa, RA., Cortes, J.[2021]

In the REALISE phase 2 study involving 51 anemic myelofibrosis patients, a novel dosing strategy of ruxolitinib led to a 70% reduction in spleen size, indicating its efficacy in managing splenomegaly associated with the condition.

Despite concerns about anemia, the study found that ruxolitinib did not worsen hemoglobin levels or increase transfusion needs, suggesting it can be safely administered even in patients with anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a novel dosing strategy for ruxolitinib in the treatment of patients with myelofibrosis and anemia: the REALISE phase 2 study. Cervantes, F., Ross, DM., Radinoff, A., et al.[2022]

JAK inhibitors are the primary treatment for myelofibrosis, effectively reducing symptoms and spleen size, but they do not significantly alter disease progression and can worsen blood cell counts in some patients.

Research is ongoing for new therapies targeting different mechanisms, such as epigenetic modification and apoptosis, which may offer alternatives for patients who cannot tolerate JAK inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel treatments for myelofibrosis: beyond JAK inhibitors. Tremblay, D., Mesa, R.[2022]

In a phase 2 trial involving 34 patients with myelofibrosis who were not responding well to ruxolitinib, the addition of navitoclax led to a significant reduction in spleen volume and improved symptoms, indicating its efficacy as a combination treatment.

Patients showing improvements in bone marrow fibrosis or a reduction in variant allele frequency had better overall survival, suggesting that navitoclax may modify the disease progression in myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of navitoclax to ongoing ruxolitinib treatment in patients with myelofibrosis (REFINE): a post-hoc analysis of molecular biomarkers in a phase 2 study. Pemmaraju, N., Garcia, JS., Potluri, J., et al.[2022]

Ruxolitinib, a JAK1/JAK2 inhibitor, has been shown to significantly reduce splenomegaly and improve symptoms and quality of life in patients with myelofibrosis, outperforming conventional chemotherapy.

Clinical trials indicate that ruxolitinib not only improves survival rates compared to placebo and best available therapies but also reduces JAK2 allele burden and stabilizes fibrosis in about 50% of patients, highlighting its effectiveness in modifying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How ruxolitinib modified the outcome in myelofibrosis: focus on overall survival, allele burden reduction and fibrosis changes. Massaro, F., Molica, M., Breccia, M.[2021]

The study found that bone marrow fibroblasts in myelofibrosis patients are not part of the malignant cell clone, which challenges previous assumptions about their origin.

Two FDA-approved immunosuppressive drugs, cyclosporine and mycophenolate mofetil, were identified as effective in reducing fibroblast collagen production, suggesting they could be potential treatments to inhibit bone marrow fibrosis in myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fibroblast dynamics as an in vitro screening platform for anti-fibrotic drugs in primary myelofibrosis. Tomuleasa, C., Selicean, S., Gafencu, G., et al.[2022]

The combination of ruxolitinib and nilotinib showed a synergistic effect against myelofibrosis (MF) cells, with a significant reduction in drug concentration needed to achieve efficacy, indicating a promising new treatment strategy.

Adding prednisone to the ruxolitinib/nilotinib combination further enhanced its effectiveness by inhibiting key signaling pathways involved in MF, suggesting a multi-faceted approach to therapy that targets both proliferation and fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib in combination with prednisone and nilotinib exhibit synergistic effects in human cells lines and primary cells from myeloproliferative neoplasms. Cortés, AA., Diaz, RA., Hernández-Campo, P., et al.[2022]

Ruxolitinib, the first FDA-approved treatment for myelofibrosis, significantly reduced spleen volume by ≥ 35% in 42% of patients compared to only 1% in the placebo group, demonstrating its efficacy in treating this condition.

While ruxolitinib effectively improved symptoms and spleen size, it was associated with increased risks of severe anemia, thrombocytopenia, and neutropenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration approval: ruxolitinib for the treatment of patients with intermediate and high-risk myelofibrosis. Deisseroth, A., Kaminskas, E., Grillo, J., et al.[2022]

Ruxolitinib is an effective oral treatment for intermediate- or high-risk myelofibrosis, targeting JAK1 and JAK2 to reduce spleen size and improve symptoms, as demonstrated in Phase III trials with significant improvements in quality of life and overall survival.

The treatment has a manageable safety profile, with common side effects including anemia and thrombocytopenia, and requires dosage adjustments based on platelet counts, allowing for personalized patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib for the treatment of primary myelofibrosis. Swaim, SJ.[2021]

Citations

1. investors.karyopharm.com investors.karyopharm.com/2025-11-03-Karyopharm-Reports-Third-Quarter-2025-Financial-Results-and-Highlights-Recent-Company-Progress

Karyopharm Reports Third Quarter 2025 Financial Results ... Top-Line Data from the Phase 3 SENTRY Trial in Myelofibrosis on Track for March 2026 –. – Total Revenue was $44.0 Million; U.S. XPOVIO® ...

2. investors.karyopharm.com investors.karyopharm.com/2025-05-12-Karyopharm-Reports-First-Quarter-2025-Financial-Results-and-Announces-New-Data-in-Myelofibrosis-that-Further-Suggests-Selinexor-May-Lead-to-Meaningful-Spleen-Volume-Reduction,-Symptom-Improvement,-Hemoglobin-Stabilization-and-Disease-Modificati

Karyopharm Reports First Quarter 2025 Financial Results ... Patients treated with selinexor had higher mean hemoglobin levels throughout the study duration and lower rates of red blood cell transfusions ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1002/530413/The-Efficacy-and-Safety-of-Selinexor-in

The Efficacy and Safety of Selinexor in Combination with ... Preclinical studies showed SEL decreased viable cells and colony formation both in newly diagnosed and RUX-exposed MF cells. ESSENTIAL trial ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11916360/

Selinexor plus ruxolitinib in JAK inhibitor treatment-naïve ... A Phase 1/3 study evaluating safety and efficacy of selinexor plus ruxolitinib for treatment of patients with JAK inhibitor (JAKi) treatment-naïve MF.

5. onclive.com onclive.com/view/selinexor-paves-the-way-for-more-affordable-effective-treatment-options-in-myelofibrosis

Selinexor Paves the Way for More Affordable, Effective ... Results from the phase 1 portion of the trial showed a 35% or greater reduction in spleen volume (SVR35) at weeks 12 and 24 in 71% and 79% of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04562389

NCT04562389 | Study of Selinexor in Combination With ... This is a global, multicenter, 2-part study to evaluate the efficacy and safety of selinexor plus ruxolitinib in JAK inhibitor (JAKi) treatment-naïve ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0147027224000175

Efficacy and safety of selinexor for patients with relapsed ... Selinexor is more effective when used in combination with corticosteroids and PIs compared to when used alone. It is effective in both relapsed and refractory ...