Selinexor + Pomalidomide + Dexamethasone ± Carfilzomib for Multiple Myeloma

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Mayo Clinic

Must not be taking: Antiretrovirals, Anticancer agents

Disqualifiers: Heart failure, Uncontrolled infection, HIV, others

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

Compensation: Varies

Number of Visits: 8

Duration: Up to 18 cycles (each cycle is 4 weeks)

39 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I/II trial identifies the best dose and side effects of selinexor, and how well it works when given in combination with pomalidomide and dexamethasone with or without carfilzomib in treating patients with multiple myeloma that has come back (relapsed) and does not respond to treatment with proteasome inhibitors and immunomodulatory drugs (refractory). Selinexor is an oral agent that blocks a protein called Exportin 1 (XPO1 or CRM1) that is abundant in a wide variety of cancers, including multiple myeloma. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Pomalidomide may stop the growth of blood vessels, stimulate the immune system, and kill cancer cells. Anti-inflammatory drugs, such as dexamethasone may lower the body's immune response and are used with other drugs in the treatment of some types of cancer. The addition of selinexor may allow better control of relapsed refractory multiple myeloma than is possible with pomalidomide and dexamethasone with or without carfilzomib.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you cannot be on certain treatments like other investigational agents or specific anticancer therapies shortly before joining the trial. It's best to discuss your current medications with the trial team to get a clear answer.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does mention that you should not be receiving any other investigational agents or anticancer therapies within a certain period before registration. It's best to discuss your current medications with the trial team to get specific guidance.

What data supports the effectiveness of the drug combination Selinexor, Pomalidomide, and Dexamethasone for treating multiple myeloma?

Research shows that Selinexor, when combined with other drugs like carfilzomib and dexamethasone, can help control disease in patients with relapsed or refractory multiple myeloma, even those resistant to previous treatments. Pomalidomide combined with dexamethasone has also been effective in improving survival and response rates in patients who have tried other therapies. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination Selinexor, Pomalidomide, and Dexamethasone for treating multiple myeloma?

Research shows that Selinexor, when combined with Carfilzomib and Dexamethasone, can help control disease in patients with relapsed or resistant multiple myeloma, with a notable percentage of patients experiencing a positive response. Additionally, Pomalidomide combined with Dexamethasone has been effective in improving survival and response rates in patients who have tried other treatments without success. ^{1 2 3 4 5}

Is the combination of Selinexor, Pomalidomide, Dexamethasone, and Carfilzomib safe for humans?

The combination of Selinexor, Carfilzomib, and Dexamethasone has been studied in patients with multiple myeloma, showing some serious side effects like cardiac failure and common side effects such as low blood cell counts, infections, and fatigue. Selinexor's safety profile is well-known, with side effects like low blood cell counts, fatigue, nausea, and weight loss, but these can be managed with proper care. ^{3 4 6 7 8}

Is the combination of Selinexor, Pomalidomide, Dexamethasone, and Carfilzomib safe for treating multiple myeloma?

The combination of Selinexor, Carfilzomib, and Dexamethasone has been studied for safety in multiple myeloma patients, with common serious side effects including low blood cell counts (thrombocytopenia, anemia, neutropenia), infections, and fatigue. Selinexor's side effects are predictable and manageable with proper care, but can be significant if not addressed. The addition of Pomalidomide to this combination has not been specifically detailed in the available safety data. ^{3 4 6 7 8}

What makes the drug Selinexor + Pomalidomide + Dexamethasone ± Carfilzomib unique for treating multiple myeloma?

This drug combination is unique because it includes Selinexor, a first-in-class oral selective inhibitor of nuclear export, which targets exportin-1 to help overcome resistance in relapsed or refractory multiple myeloma. Selinexor's novel mechanism of action, combined with other active antimyeloma agents, offers a new option for patients who have limited treatment choices due to resistance to other therapies. ^{3 6 7 9 10}

What makes the drug Selinexor unique for treating multiple myeloma?

Selinexor is unique because it is an oral drug that works by blocking exportin 1, a protein that helps cancer cells survive by exporting tumor-suppressor proteins out of the cell nucleus. This novel mechanism of action makes it effective in patients with multiple myeloma who have relapsed or are resistant to other treatments. ^{3 6 7 9 10}

Research Team

Prashant Kapoor, M.D.

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

Adults with relapsed refractory multiple myeloma who have previously been treated and are not responding to proteasome inhibitors and immunomodulatory drugs. Participants must be over 18, able to perform daily activities with minimal assistance (ECOG PS 0-2), capable of taking oral medication, willing to use birth control, and have adequate organ function. They cannot join if they've had major surgery within the last 21 days or have certain severe diseases, allergies specific to trial medications, active infections requiring systemic treatment within the past two weeks, or uncontrolled illnesses.

Inclusion Criteria

Ability to complete questionnaire(s) by themselves or with assistance

If you are able to have children, you must have a negative pregnancy test within 7 days before joining the study.

Your total bilirubin level should be no higher than 2 times the upper limit of normal, unless you have Gilbert's syndrome, in which case it should be no higher than 3 times the upper limit of normal.

Exclusion Criteria

I am allergic to Captisol, a substance used in some medications.

I have not had plasmapheresis within the last 28 days.

I am allergic to thalidomide, lenalidomide, or dexamethasone.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive selinexor, dexamethasone, and pomalidomide with or without carfilzomib. Treatment repeats every 28 days for up to 18 cycles.

Up to 18 cycles (each cycle is 4 weeks)

4 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 3 years

Every 3 months until progressive disease, then every 6 months

Treatment Details

Interventions

• Carfilzomib
• Dexamethasone
• Pomalidomide
• Selinexor

Trial Overview The SCOPE Trial is testing selinexor in combination with pomalidomide and dexamethasone against the same combination plus carfilzomib for treating patients whose multiple myeloma has returned after previous treatments. The study aims to find out the best dose of selinexor and its side effects when used in these combinations.

Participant Groups

Group I: Arm B (selinexor, dexamethasone, pomalidomide) Experimental Treatment 11 Interventions

Patients receive selinexor PO and dexamethasone PO on days 1, 8, 15, and 22, and pomalidomide PO on days 1-21. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT or CT and bone marrow biopsy and aspiration during screening and on the trial. Patients may optionally undergo blood sample collection during screening and on the trial.

Group II: Arm A (selinexor, dexamethasone, carfilzomib, carfilzomib) Experimental Treatment 12 Interventions

Patients receive selinexor PO and dexamethasone PO on days 1, 8 15, and 22, carfilzomib IV on days 1, 8, and 15, and pomalidomide PO on days 1-21. Treatment repeats every 28 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT or CT and bone marrow biopsy and aspiration during screening and on the trial. Patients may optionally undergo blood sample collection during screening and on the trial.

Dexamethasone is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Selinexor, a first-in-class oral medication that inhibits the nuclear export protein XPO-1, has been granted accelerated FDA approval for treating patients with penta-refractory multiple myeloma, showing promise in a challenging patient population.

Clinical data indicates that selinexor, particularly in combination with dexamethasone, represents a significant advancement in treatment options for heavily pretreated multiple myeloma patients, with ongoing studies exploring its use in earlier treatment lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor for the treatment of multiple myeloma. Podar, K., Shah, J., Chari, A., et al.[2023]

Pomalidomide, combined with low-dose dexamethasone, has been shown to be effective in treating adult patients with relapsed and refractory multiple myeloma, significantly improving progression-free survival and overall response rates compared to high-dose dexamethasone.

The treatment demonstrated a manageable safety profile and was effective across various patient subgroups, including those who were refractory to previous therapies, indicating its potential as a valuable salvage therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. Scott, LJ.[2022]

In a phase I trial involving 21 patients with relapsed/refractory multiple myeloma, the combination of selinexor, carfilzomib, and dexamethasone was found to be tolerable, with a recommended phase II dose established at selinexor 60 mg, carfilzomib 20/27 mg/m2, and dexamethasone 20 mg.

The treatment resulted in significant response rates, with 71% of patients achieving at least a minimal response and a median overall survival of 22.4 months, demonstrating its efficacy even in patients who were refractory to carfilzomib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of selinexor plus carfilzomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma. Jakubowiak, AJ., Jasielec, JK., Rosenbaum, CA., et al.[2023]

The MUKtwelve trial is a phase II study investigating the efficacy of selinexor combined with cyclophosphamide and prednisolone in patients with relapsed or refractory multiple myeloma, aiming to improve treatment responses without increasing toxicity.

This trial is significant as it will be the first to evaluate the clinical effectiveness of selinexor in this specific combination, addressing the need for novel therapies that can manage the disease while minimizing cumulative treatment-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MUKtwelve protocol: a phase II randomised, controlled, open, parallel group, multicentre trial of selinexor, cyclophosphamide and prednisolone (SCP) versus cyclophosphamide and prednisolone (CP) in patients with relapsed or refractory multiple myeloma. Kendall, J., Hall, A., Roberts, S., et al.[2022]

Selinexor, a selective inhibitor of nuclear export (SINE) compound, has shown promising efficacy in treating multiple myeloma (MM), particularly in patients with 'penta-refractory' MM, which is resistant to the five most effective current treatments.

Early phase clinical trials have established a safety profile for selinexor, especially when used in combination with low-dose dexamethasone, indicating it could be a valuable addition to existing treatment strategies for MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Implications of Targeting XPO1-mediated Nuclear Export in Multiple Myeloma. Gandhi, UH., Senapedis, W., Baloglu, E., et al.[2023]

Selinexor, a first-in-class selective inhibitor of nuclear export (XPO1), has shown significant efficacy in treating relapsed refractory multiple myeloma (RRMM), leading to its FDA approval in combination with dexamethasone based on results from the pivotal phase II STORM trial.

The phase III BOSTON trial demonstrated that selinexor combined with bortezomib and dexamethasone is superior to the standard treatment of bortezomib and dexamethasone alone, although it is associated with a predictable toxicity profile that requires careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Nuclear Export Proteins in Multiple Myeloma Therapy. Richard, S., Jagannath, S.[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]

In a phase II trial involving 79 patients with multiple myeloma who were resistant to multiple treatments, the combination of selinexor and low-dose dexamethasone achieved an overall response rate of 21%, indicating some efficacy in a challenging patient population.

The treatment was particularly effective in patients with high-risk cytogenetics, showing a response rate of 35%, although it was associated with significant adverse effects, including thrombocytopenia in 59% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective Inhibition of Nuclear Export With Oral Selinexor for Treatment of Relapsed or Refractory Multiple Myeloma. Vogl, DT., Dingli, D., Cornell, RF., et al.[2023]

Selinexor, when used in combination with dexamethasone or bortezomib and dexamethasone, showed an overall response rate of 29.5% in 44 patients with relapsed or refractory myeloma, indicating its efficacy as a treatment option.

The most common side effects included fatigue and thrombocytopenia, with 56% of patients requiring dose reductions; however, these adjustments did not negatively impact progression-free survival, suggesting that selinexor can be managed safely in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real World Efficacy and Toxicity of Selinexor: Importance of Patient Characteristics, Dose Intensity and Post Progression Outcomes. Kastritis, E., Gavriatopoulou, M., Solia, E., et al.[2023]

Selinexor, an oral treatment that inhibits nuclear export of tumor suppressor proteins, showed efficacy in a case series of 3 heavily treated multiple myeloma patients, achieving partial or very good partial responses despite their advanced disease status.

The combination of selinexor with bortezomib and dexamethasone (XVd) resulted in positive outcomes similar to those seen in less heavily pretreated patients, indicating its potential as a valuable option for relapsed or refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor in Patients from Argentina with Multiple Myeloma Treated with Multiple Prior Therapies: A Case Series. Remaggi, G., Ochoa, PA., Garate, GM.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Selinexor for the treatment of multiple myeloma. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Phase 1 study of selinexor plus carfilzomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma. [2023]

4. England pubmed.ncbi.nlm.nih.gov

MUKtwelve protocol: a phase II randomised, controlled, open, parallel group, multicentre trial of selinexor, cyclophosphamide and prednisolone (SCP) versus cyclophosphamide and prednisolone (CP) in patients with relapsed or refractory multiple myeloma. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical Implications of Targeting XPO1-mediated Nuclear Export in Multiple Myeloma. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Targeting Nuclear Export Proteins in Multiple Myeloma Therapy. [2022]

7. France pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

Selective Inhibition of Nuclear Export With Oral Selinexor for Treatment of Relapsed or Refractory Multiple Myeloma. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Real World Efficacy and Toxicity of Selinexor: Importance of Patient Characteristics, Dose Intensity and Post Progression Outcomes. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Selinexor in Patients from Argentina with Multiple Myeloma Treated with Multiple Prior Therapies: A Case Series. [2022]