Selinexor + Ruxolitinib + Methylprednisolone for Multiple Myeloma

(KPT-IST-391 Trial)

Overseen By Yohana Sebhat

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Oncotherapeutics

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Ruxolitinib, Selinexor, Amyloidosis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per cycle

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of medications to treat multiple myeloma, a type of blood cancer affecting plasma cells in the bone marrow. It combines selinexor, ruxolitinib, and methylprednisolone (a corticosteroid) to determine their effectiveness in stopping cancer cell growth. The trial seeks participants with multiple myeloma that has returned or not responded to at least three different treatments, including immunotherapy and proteasome inhibitors. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use certain drugs like strong CYP3A4 inhibitors or inducers, and some medications must be stopped a few weeks before starting the trial. It's best to discuss your current medications with the trial team.

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

Research shows that the combination of Selinexor, Ruxolitinib, and Methylprednisolone is generally easy for patients to handle. One study found that patients did not experience severe side effects at the doses tested, indicating no dose-limiting toxicities. While some side effects occurred, they were not serious enough to stop the treatment.

Patients who have undergone many treatments have tolerated Ruxolitinib well when used with steroids like Methylprednisolone. The FDA has approved Selinexor for treating relapsed or refractory multiple myeloma, indicating its safety is well-documented for this condition.

Overall, the treatment appears safe based on current data, but discussing potential risks with a healthcare provider remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Selinexor, Ruxolitinib, and Methylprednisolone for treating multiple myeloma because it takes a fresh approach compared to standard treatments like chemotherapy, immunomodulatory drugs, and proteasome inhibitors. Unlike traditional therapies, Selinexor works by blocking the export of tumor suppressor proteins from the nucleus, which can lead to cancer cell death. Ruxolitinib adds another layer by targeting specific pathways that help cancer cells grow, and Methylprednisolone helps reduce inflammation and support the body's response to the other drugs. This combination has the potential to offer a more effective and targeted attack on multiple myeloma, which is why researchers are keen to explore its benefits.

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

Research has shown that the combination of Selinexor, Ruxolitinib, and methylprednisolone, which participants in this trial will receive, may effectively treat multiple myeloma. Selinexor works by retaining important proteins inside the cell, which harms cancer cells. Studies have found that this treatment is generally well tolerated, with patients responding for an average of 13.1 months and experiencing a period of 3.4 months before the disease worsens. Ruxolitinib, another component of this treatment, has demonstrated effectiveness in combination with other drugs to combat myeloma cells. Overall, this combination aims to improve treatment outcomes for people with multiple myeloma. ^{2 3 6 7 8}

Who Is on the Research Team?

James Berenson, MD

Principal Investigator

Oncotherapeutics

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed/refractory multiple myeloma who've had at least three prior treatments, including an IMiD and a PI. They must be able to consent, follow the visit schedule, and have specific levels of renal insufficiency, anemia, bone lesions or hypercalcemia. Those with certain severe health conditions are excluded.

Inclusion Criteria

I am willing and able to give written consent for the trial before any screening procedures.

I have multiple myeloma and have tried at least three different treatments.

I am taking or have taken an IMiD medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Selinexor, Ruxolitinib, and Methylprednisolone following a 3+3 dose escalation schedule

28 days per cycle

Weekly visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 months

What Are the Treatments Tested in This Trial?

Interventions

• Methylprednisolone
• Ruxolitinib
• Selinexor

Trial Overview The trial tests Selinexor combined with Ruxolitinib and Methylprednisolone in patients with multiple myeloma. Selinexor inhibits XPO1 to kill cancer cells; it's approved by FDA for this cancer type when used with other drugs.

How Is the Trial Designed?

Group I: Experimental: Selinexor/Ruxolitinib/Steroids Experimental Treatment 3 Interventions

The regimen will follow a 3+3 dose escalation schedule starting at dose level 0. Subjects enrolled at dose level 0 will receive 1) selinexor (once weekly) starting at 40 mg, 2) ruxolitinib (twice a day (BID) on days 1-28) starting at 10 mg, and 3) oral methylprednisolone (every other day (QOD)) a set dose at 40 mg. Subjects at dose level 1 will receive 1) selinexor (once weekly) 60 mg, 2) ruxolitinib (BID) on days 1-28 10 mg, and 3) methylprednisolone (QOD) 40 mg. Subjects at dose level 2 will receive 1) selinexor (once weekly) 60 mg, 2) ruxolitinib (BID) on days 1-28 15 mg, and 3) oral methylprednisolone (QOD) 40 mg.

Who Is Running the Clinical Trial?

Oncotherapeutics

Lead Sponsor

Trials

23

Recruited

940+

Published Research Related to This Trial

In a phase 1 study involving 84 patients with relapsed or refractory multiple myeloma, the combination of oral selinexor and dexamethasone showed a significant increase in efficacy, achieving a 50% objective response rate compared to a modest 4% with selinexor alone.

The most common side effects were manageable and primarily grade 1 or 2, with thrombocytopenia being the most notable severe adverse event at 45%, indicating that while selinexor is effective, monitoring for blood-related side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia. Chen, C., Siegel, D., Gutierrez, M., et al.[2021]

In a phase I trial involving 28 patients with relapsed/refractory multiple myeloma, ruxolitinib combined with lenalidomide and methylprednisolone showed a clinical benefit rate of 46% and an overall response rate of 38%, indicating its potential effectiveness in overcoming resistance to lenalidomide.

The trial reported no dose-limiting toxicities, suggesting that ruxolitinib is safe to use in this combination therapy, although some patients experienced grade 3 or 4 adverse events like anemia and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study of Ruxolitinib, Lenalidomide, and Steroids for Patients with Relapsed/Refractory Multiple Myeloma. Berenson, JR., To, J., Spektor, TM., et al.[2021]

In a study involving 29 patients with multiple myeloma who had undergone extensive prior treatments, the combination of ruxolitinib and methylprednisolone showed a 31% overall response rate, indicating significant clinical activity in this heavily-treated population.

The treatment was well tolerated, with a median duration of response of 13.1 months and median progression-free survival of 3.4 months, suggesting that JAK inhibitors may be a promising option for patients with multiple myeloma, including those with high-risk cytogenetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib and methylprednisolone for treatment of patients with relapsed/refractory multiple myeloma. Berenson, JR., Martinez, D., Safaie, T., et al.[2023]

Selinexor combined with dexamethasone has shown improved response rates and duration in heavily pretreated multiple myeloma patients compared to traditional treatments, without causing excessive toxicity.

The combination of selinexor with other agents like bortezomib, carfilzomib, and IMiDs has demonstrated a durable response and a tolerable safety profile, making it a promising option for patients with relapsed and refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of selinexor-based regimens for relapsed/refractory multiple myeloma: a systematic review of literature. Masood, A., Iqbal, Q., Ehsan, H., et al.[2022]

In the phase 3 BOSTON trial, the combination of selinexor, bortezomib, and dexamethasone significantly improved progression-free survival in adults with previously treated multiple myeloma compared to the standard bortezomib-dexamethasone regimen.

This triplet therapy demonstrated a manageable safety profile, with a lower incidence of peripheral neuropathy compared to the standard treatment, making it a promising option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor-Bortezomib-Dexamethasone: A Review in Previously Treated Multiple Myeloma. Syed, YY.[2023]

Selinexor-based treatments, particularly the combination of selinexor, dexamethasone, and proteasome inhibitors (SEL + DEX + PIs), showed higher efficacy in treating multiple myeloma, with an overall response rate of 54% compared to 24% for the SEL + DEX combination.

The SEL + DEX + PIs regimen also demonstrated lower incidences of severe adverse events, such as hyponatremia and anemia, indicating a better safety profile compared to the SEL + DEX treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials. Tao, Y., Zhou, H., Niu, T.[2021]

In a phase 3 trial involving 402 patients with previously treated multiple myeloma, the combination of selinexor, bortezomib, and dexamethasone resulted in a median progression-free survival of 13.93 months, significantly longer than the 9.46 months observed with standard bortezomib and dexamethasone (p=0.0075).

The selinexor combination therapy was associated with lower rates of peripheral neuropathy (21%) compared to the standard treatment (34%), suggesting a safer profile regarding this common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Grosicki, S., Simonova, M., Spicka, I., et al.[2022]

Selinexor is a first-in-class oral medication that works by inhibiting nuclear export, leading to the retention of oncogene mRNAs and reactivation of tumor suppressor proteins, which triggers cell death in multiple myeloma (MM) cells.

In clinical studies, selinexor has shown manageable side effects and promising effectiveness in treating relapsed and refractory MM, indicating its potential to improve outcomes for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor for the treatment of patients with previously treated multiple myeloma. Mo, CC., Jagannath, S., Chari, A., et al.[2022]

Ruxolitinib, when combined with lenalidomide and methylprednisolone, shows potential to overcome resistance to lenalidomide in patients with relapsed/refractory multiple myeloma, achieving a clinical benefit rate of 49% and an overall response rate of 36% in a Phase I trial with 49 participants.

The trial demonstrated that ruxolitinib was safe, with no dose-limiting toxicities reported, although some patients experienced grade 3 or 4 adverse events, including anemia and decreased lymphocyte count, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 study of ruxolitinib, steroids and lenalidomide for relapsed/refractory multiple myeloma patients. Berenson, JR., Kim, C., Bujarski, S., et al.[2022]

Citations

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A Trial of Selinexor, Ruxolitinib and Methylprednisolone This proposed study aims to investigate the efficacy of a lower dose of Selinexor in combination with Ruxolitinib and methylprednisolone for ...

2. withpower.com withpower.com/trial/phase-1-neoplasms-plasma-cell-2-2024-c23b8

Selinexor + Ruxolitinib + Methylprednisolone for Multiple ... The treatment was well tolerated, with a median duration of response of 13.1 months and median progression-free survival of 3.4 months, suggesting that JAK ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06225310/a-trial-of-selinexor-ruxolitinib-and-methylprednisolone

A Trial of Selinexor, Ruxolitinib and Methylprednisolone Preliminary experiments have shown that Ruxolitinib, in combination with lenalidomide and dexamethasone, effectively inhibits MM cell ...

4. imbcr.org imbcr.org/news/

News Ruxolitinib/Selinexor Combo Is Being Evaluated for Multiple Myeloma: Article Ruxolitinib Elicits Few Adverse Effects When Treating Multiple Myeloma: Article ...

5. cancernetwork.com cancernetwork.com/view/ruxolitinib-selinexor-combo-is-being-evaluated-for-multiple-myeloma

Ruxolitinib/Selinexor Combo Is Being Evaluated for ... Combination therapy with JAK inhibitors may help improve efficacy outcomes for patients with multiple myeloma.

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A Trial of Selinexor, Ruxolitinib and Methylprednisolone Members are chosen based on the scientific skills and knowledge needed to monitor the particular trial. Also called a data safety and monitoring board, or DSMB.

7. ctv.veeva.com ctv.veeva.com/study/a-trial-of-selinexor-ruxolitinib-and-methylprednisolone

A Trial of Selinexor, Ruxolitinib and Methylprednisolone Clinical results indicate that Ruxolitinib in combination with steroids is well-tolerated in heavily treated MM patients. This proposed study ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.8048

A phase I trial of ruxolitinib, lenalidomide, and ... Therefore, a phase 1 trial was conducted to determine the safety and efficacy of RUX in combination with LEN and methylprednisolone (MP) for relapsed/refractory ...