Selinexor + Ruxolitinib for Myelofibrosis

(SENTRY Trial)

Not currently recruiting at 205 trial locations

Overseen By Mohit Narang

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Karyopharm Therapeutics Inc

Must be taking: JAK inhibitors

Must not be taking: JAK inhibitors, XPO1 inhibitors

Disqualifiers: Accelerated phase, Blast phase, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness and safety of combining selinexor and ruxolitinib for treating myelofibrosis, a rare bone marrow disorder that disrupts blood cell production, in individuals who have not previously tried JAK inhibitor treatments. The study compares this drug combination to a placebo plus ruxolitinib to determine which better eases symptoms and manages the condition. Suitable participants include those diagnosed with myelofibrosis who experience active symptoms like fatigue or night sweats. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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 combining selinexor and ruxolitinib holds promise for safety in patients with myelofibrosis. In earlier studies, patients tolerated the selinexor and ruxolitinib combination well. Side effects occurred but were generally manageable, with nausea and fatigue being the most common, typical of cancer treatments.

The treatment's progression to a phase 3 trial indicates a good safety record in earlier stages, suggesting that many patients have taken these drugs together without major safety issues.

Ruxolitinib has already received FDA approval for treating certain conditions, providing some confidence in its safety. Meanwhile, selinexor is under careful study for safety when used with ruxolitinib, and the results so far are encouraging. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Selinexor and Ruxolitinib for treating myelofibrosis because it offers a new approach compared to the standard treatments, which typically involve JAK inhibitors like Ruxolitinib alone. Selinexor introduces a different mechanism by inhibiting XPO1, a protein involved in exporting tumor suppressor proteins out of the cell nucleus, thereby potentially enhancing the effectiveness of Ruxolitinib. This dual action could not only improve symptom management but also target the underlying disease process more effectively. By combining these mechanisms, there's hope for better patient outcomes and improved quality of life for those suffering from this challenging condition.

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

Research has shown that the combination of selinexor and ruxolitinib, which participants in this trial may receive, may effectively treat myelofibrosis, particularly in those who haven't used JAK inhibitors before. In earlier studies, 92% of patients experienced a significant decrease in spleen size, a common issue with myelofibrosis. Additionally, 69% of patients reported feeling better overall, and 65% had stable or improved hemoglobin levels, which are important for energy and well-being. These findings suggest that this drug combination could effectively manage myelofibrosis symptoms while keeping the disease under control. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

Adults diagnosed with primary or secondary myelofibrosis, showing significant spleen enlargement and certain risk levels. They must have functioning major organs, no prior treatments with JAK inhibitors or selinexor, not be pregnant or breastfeeding, agree to use contraception, and have a life expectancy over 6 months. Exclusions include recent surgeries, uncontrolled infections without stable treatment for hepatitis B/C or HIV.

Inclusion Criteria

I have hepatitis B but have been on antiviral therapy for over 8 weeks and my viral load is under 100 IU/mL.

I will use effective birth control and not donate sperm during and for 90 days after treatment.

I have been diagnosed with a specific type of bone marrow disorder according to the latest standards.

Exclusion Criteria

I have a history of high blood pressure in the lungs.

Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the participants safety, prevent the participant from giving informed consent, or being compliant with the study procedures, or confound the ability to interpret study results.

I cannot tolerate two different anti-nausea medications for at least 2 treatment cycles.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Open-label evaluation of the safety and recommended Phase 2 dose (RP2D) of selinexor in combination with ruxolitinib, including dose escalation and expansion

Varies per cohort

Weekly visits for dosing

Phase 3 Treatment

Double-blind, placebo-controlled part of the study comparing the efficacy and safety of selinexor + ruxolitinib with placebo + ruxolitinib

28-day cycles

Weekly visits for dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib
• Selinexor

Trial Overview The trial is testing the combination of Selinexor and Ruxolitinib against a placebo plus Ruxolitinib in patients who haven't used JAK inhibitors before. It's split into two phases: an initial phase to determine safe dosages followed by a larger phase where participants are randomly assigned to either the drug combo or placebo in a 2:1 ratio.

How Is the Trial Designed?

Group I: Phase 3: Selinexor 60 mg + Ruxolitinib BID Experimental Treatment 2 Interventions

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.

Group II: Phase 1b: Selinexor and Ruxolitinib BID Experimental Treatment 2 Interventions

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.

Group III: Phase 1a: Cohort 2: Selinexor 60 mg + Ruxolitinib BID Experimental Treatment 2 Interventions

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.

Group IV: Phase 1a: Cohort 1: Selinexor 40 mg + Ruxolitinib BID Experimental Treatment 2 Interventions

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.

Group V: Phase 3: Placebo + Ruxolitinib BID Active Control 2 Interventions

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.

Ruxolitinib is already approved in United States, European Union for the following indications:

Approved in United States as Jakafi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Vitiligo

Approved in European Union as Jakavi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Non-segmental vitiligo

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

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 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]

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]

Ruxolitinib, a JAK1/JAK2 inhibitor, was evaluated in a large phase 3b study (N = 2233) for treating myelofibrosis, including patients with low platelet counts, showing significant reductions in spleen size and symptoms.

The safety profile of ruxolitinib was consistent with previous studies, with common adverse events like anemia and thrombocytopenia, but these rarely led to treatment discontinuation, indicating it is a viable option for patients with low platelet counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary analysis of JUMP, a phase 3b, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts. Al-Ali, HK., Griesshammer, M., Foltz, L., et al.[2021]

Ruxolitinib is a dual inhibitor of JAK1 and JAK2, which are crucial in the development of myelofibrosis (MF), and it has been FDA-approved since November 2011 for treating intermediate or high-risk MF.

The review discusses Ruxolitinib's current role in managing MF and explores its potential future applications in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus activated kinase inhibition in myelofibrosis. Malhotra, H.[2021]

In a phase II study, ruxolitinib, starting at a low dose of 5 mg twice daily, showed significant efficacy in myelofibrosis patients with low platelet counts (50-100 × 10^9/L), with 62% of patients achieving stable doses of 10 mg twice daily by week 24, and median reductions in spleen volume and symptoms of 24.2% and 43.8%, respectively.

While some patients experienced thrombocytopenia requiring dose adjustments, the treatment was generally manageable, with mean hemoglobin levels remaining stable, indicating that ruxolitinib can be safely administered to this subset of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. Talpaz, M., Paquette, R., Afrin, L., et al.[2021]

Ruxolitinib is a selective oral inhibitor of JAK1 and JAK2 that effectively reduces spleen size and alleviates symptoms in patients with myelofibrosis, showing a 41.9% spleen-volume response rate compared to only 0.7% for placebo in a Phase III trial.

Patients taking ruxolitinib also experienced significant improvements in their overall quality of life and symptom scores, with 45.9% showing a ≥ 50% improvement compared to 5.3% for placebo, although the treatment was associated with thrombocytopenia as a dose-limiting toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis. Ostojic, A., Vrhovac, R., Verstovsek, S.[2021]

Citations

1. 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.

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 ... Karyopharm reports first quarter 2025 financial results and announces new data in myelofibrosis that further suggests selinexor may lead to meaningful spleen ...

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 ... Besides, a phase I study reported, with SEL plus RUX in treatment-Naïve MF, 92% patients(pts) achieved SVR35, 69% had symptom response and 65% had stable or ...

4. 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 ...

5. targetedonc.com targetedonc.com/view/selinexor-with-ruxolitinib-continues-to-demonstrate-efficacy-in-myelofibrosis

Selinexor With Ruxolitinib Continues to Demonstrate ... Selinexor with ruxolitinib demonstrated encouraging efficacy with a manageable safety profile in patients with myelofibrosis who were previously treated with ...

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4578/505747/The-Efficacy-and-Safety-of-Selinexor-in

The Efficacy and Safety of Selinexor in Combination with ... We have presented promising efficacy and safety data in real-world setting of SEL plus RUX regimen in MF patients in 2023 EHA. Here we are to ...

7. investors.karyopharm.com investors.karyopharm.com/2023-06-28-Karyopharm-Initiates-Pivotal-Phase-3-Study-of-XPO1-Inhibitor-Selinexor-and-Ruxolitinib-in-JAK-Inhibitor-JAKi-Naive-Myelofibrosis

Karyopharm Initiates Pivotal Phase 3 Study of XPO1 ... The randomized, double-blind, placebo-controlled study is expected to enroll 306 JAKi-naive patients with intermediate or high-risk myelofibrosis.