Selinexor for Smoldering Multiple Myeloma

Overseen By Jodi Lipof

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Rochester

Must not be taking: Systemic corticosteroids

Disqualifiers: Symptomatic MM, Amyloidosis, Active malignancy, 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: 48 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether low-dose selinexor can delay the progression of smoldering multiple myeloma, a blood condition, into symptomatic multiple myeloma. Selinexor is already used to treat multiple myeloma but is being explored here for earlier intervention. Suitable candidates for this trial have intermediate to high-risk smoldering multiple myeloma and do not yet show symptoms like bone damage or severe anemia (low red blood cell count). Participants will take selinexor weekly for up to 12 cycles to determine if it slows disease progression. As a Phase 2 trial, this 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 information does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids over 10mg of prednisone daily, you may not be eligible to participate.

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

Research shows that selinexor, a drug approved for treating active multiple myeloma, is now being tested for safety in people with smoldering multiple myeloma, a condition where patients risk developing full multiple myeloma. Earlier studies found that selinexor was generally well-tolerated.

The FDA has approved selinexor for other types of multiple myeloma, indicating some confidence in its safety. In these studies, some patients experienced side effects, but they were manageable and did not outweigh the treatment's benefits. Common side effects included tiredness, nausea, and low blood counts, which are typical in cancer treatments.

Overall, selinexor's safety in treating multiple myeloma suggests promise for its use in smoldering multiple myeloma, although side effects should be considered. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for smoldering multiple myeloma?

Selinexor is unique because it works differently than most treatments for smoldering multiple myeloma. While standard treatments often involve therapies like proteasome inhibitors, immunomodulatory drugs, or monoclonal antibodies, Selinexor targets XPO1, a protein involved in transporting cancer-related proteins out of the cell nucleus. By inhibiting XPO1, Selinexor keeps these proteins inside the nucleus, leading to cancer cell death. Researchers are excited about this approach because it offers a novel mechanism that could be effective for patients who might not respond well to conventional treatments.

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

Research has shown that selinexor effectively treats multiple myeloma, a type of blood cancer. Selinexor blocks certain proteins in cancer cells, causing the cells to die. Studies have found that selinexor benefits patients with relapsed or refractory multiple myeloma, improving their condition when other treatments have failed. It is already approved for use in patients with active multiple myeloma. In this trial, researchers are testing selinexor for smoldering multiple myeloma, an early form of the disease, with the hope that it might slow its progression to full-blown multiple myeloma. This hope is based on its success in treating active multiple myeloma. ^{2 4 6 7 8}

Who Is on the Research Team?

Jodi Lipof

Principal Investigator

University of Rochester

Are You a Good Fit for This Trial?

This trial is for adults over 18 with intermediate to high-risk Smoldering Multiple Myeloma (SMM), which hasn't progressed to full-blown multiple myeloma. Participants need proper liver and kidney function, no severe bone damage from the disease, and a life expectancy of more than a year. They must not have other active cancers or infections, be pregnant, or refuse effective contraception.

Inclusion Criteria

You must have certain levels of specific substances in your blood, healthy liver and kidney function, and good blood cell counts. You must also have a good life expectancy, be in good overall health, and use effective birth control during the study.

I have been diagnosed with smoldering multiple myeloma as per IMWG standards.

I don't have high calcium, anemia, bone damage, or kidney issues due to my blood disorder.

Exclusion Criteria

You have certain symptoms related to a plasma cell disorder, such as high calcium levels, kidney problems, anemia, bone lesions, or specific levels of plasma cells and proteins in your blood. You also have other medical conditions or treatments that may interfere with the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Selinexor 40mg weekly for up to 12 cycles, with each cycle being 28 days in length

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Selinexor

Trial Overview The study tests low-dose Selinexor in patients with SMM at intermediate or high risk of developing symptomatic multiple myeloma. The goal is to see if Selinexor can delay the progression of SMM to an active form of cancer.

How Is the Trial Designed?

Group I: Experimental: Treatment Experimental Treatment 1 Intervention

Selinexor 40mg weekly for up to 12 cycles. Each cycle will be 28 days in length.

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?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11940887/

Selinexor's Immunomodulatory Impact in Advancing Multiple ... Selinexor leads to the inactivation of cancer-related proteins and induces apoptosis by disrupting the nucleocytoplasmic flow in myeloma cells.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04877275

ATG-010(Selinexor) in Combination With Chemotherapy ... This is a single-arm and open-label phase II study of Relapsed/Refractory Multiple Myeloma patients who have received at least one prior lines of treatment ...

3. xpovio.com xpovio.com/multiple-myeloma/clinical-trial-results

Clinical Trial Results See clinical trial results that show how XPOVIO® worked for adults with multiple myeloma who experienced at least one relapse.

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2019/212306Orig1s000MultidisciplineR.pdf

XPOVIO (Selinexor) MULTI-DISCIPLINE REVIEW XPOVIO is indicated in combination with dexamethasone, for the treatment of patients with relapsed refractory multiple myeloma who have received ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02336815

NCT02336815 | Selinexor Treatment of Refractory Myeloma Optimal Supportive Care With Selinexor Improves Outcomes in Patients With Relapsed/Refractory Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2021 Dec;21(12): ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02389543

Study of Selinexor (KPT- 330), Lenalidomide, & ... This is an open-label, randomized clinical study with two stages to assess the maximum tolerated dose (MTD), efficacy, and safety of selinexor, lenalidomide, ...

7. myeloma.org myeloma.org/xpovio-selinexor

Xpovio (selinexor) Xpovio (selinexor), a nuclear export inhibitor, is FDA-approved for use in the treatment of relapsed or refractory multiple myeloma.

8. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/6729/505114/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.