Selinexor for Myelofibrosis

Not currently recruiting at 42 trial locations

Overseen By Karyopharm Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Karyopharm Therapeutics Inc

Must be taking: JAK inhibitors

Must not be taking: Strong CYP3A inhibitors, inducers

Disqualifiers: Accelerated phase, Selinexor, GI impairment, 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: 28-day cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called selinexor for people with myelofibrosis, a type of blood cancer. The goal is to assess the safety and effectiveness of selinexor compared to treatments chosen by doctors. Participants will be randomly assigned to receive either selinexor or another treatment. Suitable candidates have tried JAK inhibitors for at least six months but still experience issues like an enlarged spleen or difficulty tolerating the treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot use any anti-MF therapy within 21 days before starting the trial. Also, you should not have taken strong CYP3A inhibitors or inducers shortly before starting selinexor.

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. In one study, patients generally tolerated selinexor well. Some participants experienced side effects, but these were manageable. Common side effects included nausea and tiredness, typical with many treatments. Another study found that selinexor, especially when combined with other medications, may help treat challenging cases of myelofibrosis. Overall, despite the side effects, selinexor has a safety profile that supports further research for treating myelofibrosis. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myelofibrosis?

Unlike the standard treatments for myelofibrosis, which typically include JAK 1/2 inhibitors, selinexor offers a novel approach by targeting the nuclear export protein XPO1. This unique mechanism helps in the regulation of proteins that control cell growth and survival, potentially providing a new way to manage this condition. Researchers are excited about selinexor because it represents a different method that could benefit patients who have not responded well to existing therapies. Additionally, selinexor's oral administration makes it a convenient option for patients, possibly improving adherence and quality of life.

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

Research has shown that selinexor, which participants in this trial may receive, might help people with myelofibrosis by reducing spleen size and easing symptoms. Studies have found that patients taking selinexor had higher hemoglobin levels, potentially reducing the need for blood transfusions. This is particularly important for those who haven't had success with JAK inhibitors. Early results also suggest that selinexor, especially when combined with ruxolitinib, can help manage myelofibrosis. Overall, the evidence suggests selinexor could offer significant benefits to people with this condition. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

Adults diagnosed with myelofibrosis who have been treated with JAK inhibitors for at least 6 months can join. They must be in good general health, not pregnant or breastfeeding, and willing to use contraception. People cannot join if they have a high percentage of blasts in blood or bone marrow, severe gastrointestinal issues affecting drug absorption, recent major surgery, life-threatening conditions, or previous treatment with selinexor.

Inclusion Criteria

I am a man who will use effective birth control during and for 3 months after the study, and won't donate sperm.

My spleen is enlarged, measuring over 450 cm^3 on an MRI or CT scan.

I have hepatitis C but my viral load is undetectable.

Exclusion Criteria

I do not have severe GI issues that could affect medication absorption.

I haven't taken any standard or experimental treatments for myelofibrosis in the last 21 days, except for hydroxyurea or growth factors.

I haven't taken strong CYP3A affecting drugs within the last week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either selinexor or physician's choice treatment. Selinexor is administered as 80 mg for the first 2 cycles followed by 60 mg once weekly in subsequent cycles.

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Selinexor

Trial Overview The trial is testing the safety and effectiveness of Selinexor compared to other treatments chosen by physicians for those with myelofibrosis previously treated with JAK inhibitors. Participants will be randomly assigned to either receive Selinexor or a physician's choice treatment in an open-label study.

How Is the Trial Designed?

Group I: Arm S: Selinexor Experimental Treatment 1 Intervention

Participants with MF who had previously received at least 6 months of treatment with JAK 1/2 inhibitor will receive a dose of selinexor 80 mg for first 2 cycles followed by selinexor 60 mg once weekly (QW) in subsequent cycles orally on Days 1, 8, 15, and 22 of each 28-day cycle to participants on Arm S.

Group II: Arm PC: Physician's Choice Treatment Active Control 1 Intervention

Participants with MF who had previously received at least 6 months of treatment with JAK 1/2 inhibitor will receive Physician's choice treatment which will be administered as per clinical practice.

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

Citations

1. 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 ...

2. investors.karyopharm.com investors.karyopharm.com/2025-09-10-Karyopharm-Announces-Completion-of-Enrollment-in-the-Phase-3-SENTRY-Trial-in-Myelofibrosis

Karyopharm Announces Completion of Enrollment in the ... "Selinexor plus ruxolitinib has the potential to be the first combination therapy approved for the treatment of myelofibrosis, depending on the ...

3. 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.

4. 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 ...

5. 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 showed SEL's ...

6. investors.karyopharm.com investors.karyopharm.com/2023-03-14-Karyopharm-Announces-Updated-Selinexor-Data-in-Patients-with-Treatment-Naive-Myelofibrosis-to-be-Presented-at-AACR-2023

Karyopharm Announces Updated Selinexor Data in ... Updated efficacy, including ≥35% reduction in spleen volume (SVR35) and ≥50% reduction in symptom scores (TSS50), and safety data will be ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03627403

Study Details | NCT03627403 | Selinexor in Myelofibrosis ... This is a phase II, open label, prospective, single-arm study evaluating the efficacy and safety of selinexor in patients with PMF or secondary MF (PPV-MF ...

8. 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 ...