Selinexor for Multiple Myeloma

Overseen By Mark A Schroeder, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: XPO1 inhibitors

Disqualifiers: Active CNS involvement, Progressive disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of selinexor as a treatment for people with multiple myeloma, a type of blood cancer, who haven't responded well to other therapies and have undergone CAR-T cell therapy. Researchers aim to determine if selinexor can safely prevent cancer growth after CAR-T treatment. It may suit individuals who have received CAR-T therapy but still show signs of cancer and have difficult-to-treat multiple myeloma. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take any other treatments for multiple myeloma during the study. You may continue corticosteroids if they are for conditions other than multiple myeloma.

Is there any evidence suggesting that selinexor is likely to be safe for humans?

Research has shown that selinexor, tested in patients with multiple myeloma, is effective but can cause side effects. The most common side effects include nausea, vomiting, diarrhea, tiredness, and loss of appetite. While these side effects are often manageable, some patients have discontinued treatment because of them.

A review of selinexor treatments in multiple myeloma found that the drug generally works well, with side effects that most people can handle. However, some patients did stop using it due to these side effects. This indicates that while selinexor can be effective, careful monitoring is necessary to manage any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Selinexor is unique because it targets a protein called XPO1, which plays a crucial role in cancer cell survival. Unlike many standard treatments for multiple myeloma, such as proteasome inhibitors and immunomodulatory drugs, selinexor works by inhibiting this protein, leading to the accumulation of tumor-suppressing proteins in the nucleus and ultimately causing cancer cell death. Researchers are excited about selinexor because it offers a novel mechanism of action that might be effective for patients who have a high risk of relapse, potentially providing a new option where existing treatments may not be sufficient.

What evidence suggests that selinexor might be an effective treatment for multiple myeloma?

Previous studies have shown that selinexor holds promise in treating multiple myeloma, particularly when combined with other treatments. Research indicates that selinexor can help prevent cancer progression for an average of 4.7 months. In this trial, participants will receive selinexor, which is most effective when used with corticosteroids and proteasome inhibitors (PIs). Selinexor directly targets cancer cells and does not interfere with T-cell collection for CAR-T therapy, making it a safe option for patients undergoing this advanced cancer treatment. ^{2 6 7 8 9}

Who Is on the Research Team?

Mark A Schroeder, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for patients with multiple myeloma who have not responded well to triple-therapy and have undergone CAR-T therapy. It's specifically aimed at those with high-risk features like adverse risk cytogenetics, less than complete response post CAR-T, or extramedullary disease.

Inclusion Criteria

Presence of extramedullary disease documented prior to receiving CAR-T

The effects of selinexor on the developing human fetus are unknown. Women of childbearing potential and men must agree to use adequate contraception

Ability to understand and willingness to sign an IRB approved written informed consent document

Exclusion Criteria

History of allergic reactions to compounds of similar composition to selinexor

Pregnant and/or breastfeeding

Currently receiving any other investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive selinexor starting on Day 30 after CAR-T infusion for up to 12 cycles, with weekly doses on Days 1, 8, 15, and 22 of each 28-day cycle

12 months

Weekly visits for dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of complete response and progression-free survival

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Selinexor

Trial Overview The study tests Selinexor as a maintenance treatment after CAR-T cell therapy in multiple myeloma patients. The goal is to see if it can improve minimal residual disease rates and extend the time without disease progression.

How Is the Trial Designed?

Group I: Selinexor Experimental Treatment 1 Intervention

Patients with high risk of relapse will receive selinexor beginning on Day 30 after cilta-cel infusion for up to 12 cycles (initiation of treatment may be delayed for up to 28 days in the event that MRD results are outstanding or a patient is experiencing ongoing cytopenias). Selinexor will be given weekly on Days 1, 8, 15, and 22 of each 28-day cycle. The first 3 to 6 patients enrolled will be part of the safety run-in cohort; these patients will be monitored for dose-limiting toxicities during Cycle 1. Provided the safety run-in shows that selinexor is safe and tolerable at this dose, an additional 14 to 17 patients (for a total of 20) will be enrolled.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Karyopharm Therapeutics Inc

Industry 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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40422527/

Real-World Treatment Patterns and Survival Outcomes of ... Patients had a real-world overall survival (rwOS) of 14.7 months (95% CI: 10.6, 20.9) and a derived progression-free survival (dPFS) of 4.7 ...

2. 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 ...

3. targetedonc.com targetedonc.com/view/notable-outcomes-of-selinexor-based-triplet-therapy-addressed-in-rrmm

Notable Outcomes of Selinexor-Based Triplet Therapy ... After a median follow-up of 13.2 months (IQR, 6.2-19.8) in the triplet arm and 16.5 months (IQR, 9.4-19.8) in the doublet arm, the median PFS ...

4. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1649493/full

Lower dose and weekly schedules of selinexor in multiple ... Results: Updated results on once-weekly selinexor in combination with other anti-MM agents showed a reduced adverse event profile and improved ...

5. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/7152/489718/Real-World-Efficacy-and-Toxicity-of-Selinexor

Real World Efficacy and Toxicity of Selinexor - ASH Publications Starting dose was 40-100 mg per week in 16 (37%) and >100 mg week in 28 (63%) pts. Median duration of selinexor therapy was 2.7 months. On ITT, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39905622

Safety assessment of selinexor: a real-world ... Clinical trials of selinexor in patients with multiple myeloma were reviewed. We investigated selinexor-related adverse events through data ...

7. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.758992/full

Safety and Efficacy Analysis of Selinexor-Based Treatment ... Our meta-analysis revealed that selinexor-based regimens could offer reasonable efficacy and tolerable adverse events in patients with multiple myeloma.

8. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7080/527411/Response-and-Safety-of-Selinexor-with-VRD-Regimen

Response and Safety of Selinexor with VRD Regimen in ... The combination of selinexor with VRd regimen demonstrated early, deep, and durable responses in NDMM patients with extramedullary disease, both ...

9. nature.com nature.com/articles/s41375-020-0756-6

Integrated safety profile of selinexor in multiple myeloma The most common adverse events (AEs) are gastrointestinal (nausea, vomiting, and diarrhea), constitutional (fatigue, decreased appetite), ...