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)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well a combination of medications can treat multiple myeloma, a type of blood cancer that has returned and resists standard treatments. It examines different combinations of selinexor (a new potential drug), pomalidomide, dexamethasone, and sometimes carfilzomib to determine the best doses and identify any side effects. The trial targets individuals whose multiple myeloma persists despite treatment with drugs that target cancer cell growth and immune system boosters. Those who have experienced a persistent return of symptoms despite prior treatments might be suitable candidates. 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 potential drug.

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.

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

Research has shown that the combination of selinexor, pomalidomide, and dexamethasone is generally safe for patients with relapsed or refractory multiple myeloma. In studies, this combination worked well without major safety concerns. Testing two different doses of selinexor revealed that the treatment was manageable, with most side effects being mild to moderate.

Studies have also shown that the combination of selinexor, pomalidomide, dexamethasone, and carfilzomib is safe. No treatment-related deaths were reported, and most side effects were expected and manageable. This treatment helped some patients who did not respond to other drugs.

These studies provide early safety information. While the results are promising, ongoing trials will offer more detailed safety data. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they combine innovative drugs that work differently from standard therapies. Selinexor, a standout component, works by targeting and inhibiting a protein called XPO1, which helps cancer cells grow and survive. This is different from traditional drugs that primarily target the cancer cells' DNA or the immune system. By pairing selinexor with pomalidomide and dexamethasone, and optionally carfilzomib, these treatments offer a novel approach that could potentially enhance effectiveness and overcome resistance seen with existing options. This combination could provide new hope for patients with multiple myeloma, especially those who have not responded well to standard treatments.

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

Research shows that the combination of selinexor, pomalidomide, and dexamethasone, which participants in this trial may receive, can effectively treat multiple myeloma that has returned or not responded to other treatments. Studies suggest this combination benefits patients who haven't succeeded with previous therapies. Selinexor blocks a protein necessary for cancer cell growth, potentially enhancing the effectiveness of other treatments. Another treatment arm in this trial includes adding carfilzomib, which inhibits enzymes essential for cancer cell growth, potentially boosting this effect. Evidence indicates that these combinations can be effective and are generally manageable for patients. Overall, these treatments might offer better disease control compared to current options. ^{1 2 3 5 6}

Who Is on the Research Team?

Prashant Kapoor, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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, 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]

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, 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, 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]

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1996/531788/Efficacy-and-Safety-of-Selinexor-Pomalidomide-and

Efficacy and Safety of Selinexor, Pomalidomide, and ... Efficacy and Safety of Selinexor, Pomalidomide, and Dexamethasone (SPd) for Treatment of Patients with Relapsed or Refractory Multiple Myeloma ( ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04764942

Selinexor, Pomalidomide, and Dexamethasone With or ... The addition of selinexor may allow better control of relapsed refractory multiple myeloma than is possible with pomalidomide and dexamethasone with or without ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05478993

Study Details | NCT05478993 | Selinexor, Pomalidomide, ... This is a single-arm, open-label, multicenter, exploratory study initiated by investigator to evaluate the efficacy and safety of Selinexor (S) combined ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04764942

Study Details | NCT04764942 | Selinexor, Pomalidomide, ... The addition of selinexor may allow better control of relapsed refractory multiple myeloma than is possible with pomalidomide and dexamethasone with or without ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38826786/

Efficacy and safety of once weekly selinexor 40 mg versus ... The all-oral combination of SPd exhibited preliminary signs of efficacy and was generally tolerable in patients with RRMM.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124047438

Efficacy and Safety of Selinexor, Pomalidomide, and ... The all-oral combination of SPd showed signs of preliminary efficacy and was generally tolerable in patients with RRMM.