SPd vs EloPd Chemotherapy for Multiple Myeloma

Recruiting at 100 trial locations

Overseen By European Myeloma Network (EMN)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Stichting European Myeloma Network

Must be taking: Anticoagulants

Must not be taking: Pomalidomide, Elotuzumab

Disqualifiers: Smoldering MM, Plasma cell leukemia, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

Duration: up to 2 years

222 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase 3 randomized, open-label multicenter trial will compare the efficacy, safety and the impact on health-related quality of life (HR-QoL) of SPd versus EloPd in pomalidomide-naïve patients with MM who have received 1 to 4 prior anti-MM regimens and been treated with an immunomodulatory imide drug (IMiD), proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody (mAb).

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had radiation, chemotherapy, or immunotherapy within 2 weeks prior to starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the idea that SPd vs EloPd Chemotherapy for Multiple Myeloma is an effective drug?

The available research shows that selinexor, a key component of SPd chemotherapy, is effective for treating multiple myeloma, especially in patients who have not responded to other treatments. Studies have shown that selinexor, when combined with dexamethasone, can help patients who are resistant to the five most common treatments for multiple myeloma. This combination has been approved for use in such cases, indicating its effectiveness. Additionally, selinexor has shown promising results in patients who have undergone multiple prior therapies, achieving partial or very good partial responses. This suggests that SPd chemotherapy can be a valuable option for patients with relapsed or treatment-resistant multiple myeloma. ^{1 2 3 4 5}

What safety data exists for SPd vs EloPd chemotherapy in multiple myeloma?

The safety data for selinexor, a component of the SPd regimen, indicates that it has a well-established and predictable toxicity profile. Common side effects include thrombocytopenia, anemia, neutropenia, fatigue, nausea, anorexia, and weight loss. Hyponatremia and cataracts are also noted as class effects. Adverse events reported in studies include nausea, thrombocytopenia, asthenia, and fatigue. The toxicity can be significant unless managed aggressively and preemptively. Eltanexor, a second-generation SINE compound, is being investigated for potentially better tolerability. ^{1 3 5 6 7}

Is the drug Elotuzumab, Pomalidomide, Selinexor a promising treatment for multiple myeloma?

Yes, the combination of Elotuzumab, Pomalidomide, and Dexamethasone has shown promising results in treating multiple myeloma. It has improved survival rates and response rates in patients who have tried other treatments before. This drug combination is considered effective and well-tolerated, making it a promising option for patients with relapsed or refractory multiple myeloma. ^{8 9 10 11 12}

Eligibility Criteria

This trial is for adults with previously treated multiple myeloma who've had 1-4 prior treatments but haven't used selinexor, pomalidomide, or elotuzumab. They should have adequate organ function and no major health issues that could affect the study. People with certain infections or recent transplants can't join.

Inclusion Criteria

I can take aspirin or am fully anticoagulated if I have a history of blood clots.

I might be using alternative blood thinners as decided by my doctor.

I have had 1 to 4 treatments for my multiple myeloma.

Exclusion Criteria

I have been treated with a drug like selinexor before.

In the opinion of the Investigator, patients who are below their ideal body weight and would be unduly impacted by changes in their weight

Known intolerance, hypersensitivity, or contraindication to any of the study treatments

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either SPd or EloPd treatment in 28-day cycles

up to 2 years

Day 1 of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 3 years

Every 3 months

Long-term follow-up

Progression-free survival and overall survival are assessed

up to 5 years

Treatment Details

Interventions

• Dexamethasone Oral
• Elotuzumab
• Pomalidomide
• Selinexor

Trial Overview The trial compares two drug combinations: Selinexor, Pomalidomide, and Dexamethasone (SPd) versus Elotuzumab, Pomalidomide, and Dexamethasone (EloPd). It aims to see which combo is safer and more effective for treating multiple myeloma while also looking at how they impact quality of life.

Participant Groups

Group I: Selinexor, pomalidomide and dexamethasone (SPd) Experimental Treatment 3 Interventions

Selinexor will be given as an oral dose: 40 mg (2 20 mg tablets) once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle. * Pomalidomide will be given as an oral 4 mg dose QD on Days 1 to 21 of each 28-day cycle. * Patients ≤75 years: o Dexamethasone will be given as an oral 40 mg dose QW on Days 1, 8, 15, and 22 of each 28-day cycle. Dose may be divided over 2 days at the Investigator's discretion. * Patients \> 75 years: * Dexamethasone will be given as an oral 20 mg dose QW on Days 1, 8, 15, and 22 of each 28-day cycle. Dose may be divided over 2 days at the Investigator's discretion.

Group II: Elotuzumab, Pomalidomide and Dexamethasone (EloPd) Active Control 3 Interventions

Elotuzumab will be given IV 10 mg/kg on Days 1, 8, 15, and 22 of cycle 1 and 2 then 20 mg/kg on Day 1 of cycles ≥3 of each 28-day cycle. * Pomalidomide will be given as an oral 4 mg dose once a day (QD) on Days 1 to 21 of each 28-day cycle. * Patients ≤75 years: * Dexamethasone 28 mg PO + 8 mg IV on days of elotuzumab dosing * Dexamethasone 40 mg PO on non-elotuzumab days (e.g., days 8, 15, and 22 of cycle 3 and beyond). Dose may be divided over 2 days at the Investigator's discretion. * Patients \>75 years: * Dexamethasone 8 mg PO + 8 mg IV on days of elotuzumab dosing * Dexamethasone 20 mg PO on non-elotuzumab dosing weeks (e.g., days 8, 15, and 22 of cycle 3 and beyond). Dose may be divided over 2 days at the Investigator's discretion.

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

Approved in United States as Empliciti for:

• Multiple myeloma

Approved in European Union as Empliciti for:

• Multiple myeloma

Approved in Canada as Empliciti for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Stichting European Myeloma Network

Lead Sponsor

Trials

28

Recruited

18,600+

European Myeloma Network

Lead Sponsor

Trials

27

Recruited

12,600+

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

Findings from Research

Nuclear export inhibitors (SINEs), particularly selinexor, have emerged as a promising treatment for relapsed/refractory multiple myeloma, showing cytotoxic effects on myeloma cells and potential to resensitize them to therapy.

Selinexor was approved in July 2019 based on the STORM trial, and ongoing studies are exploring its combination with standard treatments, while a second-generation SINE, eltanexor, is also being investigated for its efficacy and improved safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Nuclear Export Proteins in Multiple Myeloma Therapy. Theodoropoulos, N., Lancman, G., Chari, A.[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]

In a study involving 122 patients with triple-class refractory myeloma, the combination of selinexor and dexamethasone resulted in a partial response or better in 26% of patients, demonstrating its potential efficacy as a treatment option for those who have not responded to existing therapies.

While selinexor was associated with common side effects like fatigue and nausea, it also led to significant thrombocytopenia in 73% of patients, highlighting the need for careful monitoring of blood cell counts during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma. Chari, A., Vogl, DT., Gavriatopoulou, M., 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]

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]

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]

Selinexor, an exportin-1 inhibitor, has received regulatory approval for treating multiple myeloma and non-Hodgkin lymphomas based on pivotal trials, including the SADAL and BOSTON trials, demonstrating its potential as a monotherapy or in combination regimens.

While selinexor shows promise in overcoming treatment resistance and may have synergistic effects with other therapies, it has consistent tolerability issues, necessitating improved management strategies to enhance its efficacy compared to newer cellular and immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor therapy for multiple myeloma and non-Hodgkin lymphomas. Goldsmith, SR., Liu, L., Shiah, K.[2023]

In the phase II ELOQUENT-3 trial, the combination of elotuzumab with pomalidomide and dexamethasone (EPd) significantly improved overall survival (OS) in patients with relapsed/refractory multiple myeloma, with a median OS of 29.8 months compared to 17.4 months for the pomalidomide/dexamethasone (Pd) group.

The safety profile of EPd was consistent with previous studies, showing no new safety concerns, indicating that this treatment is both effective and safe for patients who have already undergone multiple lines of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab Plus Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Final Overall Survival Analysis From the Randomized Phase II ELOQUENT-3 Trial. Dimopoulos, MA., Dytfeld, D., Grosicki, S., et al.[2023]

The combination treatment of elotuzumab, pomalidomide, and dexamethasone (EloPd) demonstrated a 55.4% overall response rate in a real-world study of 200 patients with relapsed/refractory multiple myeloma, aligning with results from the ELOQUENT-3 trial.

The safety profile of EloPd in this cohort was manageable and similar to that observed in clinical trials, indicating it is a viable treatment option for patients who have undergone at least two prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: a multicenter, retrospective real-world experience with 200 cases outside of controlled clinical trials. Gentile, M., Vigna, E., Palmieri, S., et al.[2023]

In a phase 2 study involving 82 patients with newly diagnosed multiple myeloma (NDMM), the combination of elotuzumab, lenalidomide, and dexamethasone (ELd) showed a high overall response rate (ORR) of 88%, suggesting it is an effective treatment option for patients ineligible for stem cell transplantation.

The safety profile of ELd was favorable, with no infusion reactions reported at the accelerated infusion rate of 5 mL/min, indicating that this treatment can be well-tolerated in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab plus lenalidomide and dexamethasone for newly diagnosed multiple myeloma: a randomized, open-label, phase 2 study in Japan. Kubo, K., Hori, M., Ohta, K., et al.[2020]

Elotuzumab combined with pomalidomide and dexamethasone (E-Pd) was shown to effectively prolong progression-free survival (PFS) in patients with relapsed and refractory multiple myeloma (RRMM), based on data from 440 patients in the ELOQUENT-3 study.

The pharmacokinetics of elotuzumab were well-characterized, revealing that its exposure did not lead to an increase in severe adverse events (grade 3+ AEs), indicating a favorable safety profile when used with the Pd regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic and exposure-response analyses of elotuzumab plus pomalidomide and dexamethasone for relapsed and refractory multiple myeloma. Ide, T., Osawa, M., Sanghavi, K., et al.[2022]

In the phase III ELOQUENT-2 trial involving adults with relapsed multiple myeloma, elotuzumab combined with lenalidomide and dexamethasone significantly improved progression-free survival and overall response rates compared to the standard treatment alone.

The addition of elotuzumab did not negatively affect health-related quality of life and had a manageable safety profile, with the most common serious side effects being blood-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Lamb, YN.[2019]

References

1. France pubmed.ncbi.nlm.nih.gov

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

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

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

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

Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma. [2023]

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

Selinexor for the treatment of multiple myeloma. [2023]

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

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

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

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

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

Selinexor therapy for multiple myeloma and non-Hodgkin lymphomas. [2023]

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

Elotuzumab Plus Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Final Overall Survival Analysis From the Randomized Phase II ELOQUENT-3 Trial. [2023]

9. Italy pubmed.ncbi.nlm.nih.gov

Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: a multicenter, retrospective real-world experience with 200 cases outside of controlled clinical trials. [2023]

10. Japan pubmed.ncbi.nlm.nih.gov

Elotuzumab plus lenalidomide and dexamethasone for newly diagnosed multiple myeloma: a randomized, open-label, phase 2 study in Japan. [2020]

11. Germany pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic and exposure-response analyses of elotuzumab plus pomalidomide and dexamethasone for relapsed and refractory multiple myeloma. [2022]

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

Elotuzumab: A Review in Relapsed and/or Refractory Multiple Myeloma. [2019]