Selinexor Combination Therapy for Multiple Myeloma

Recruiting at 28 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Strong CYP3A4 inhibitors, inducers

Disqualifiers: Uncontrolled illness, Allergic reactions, 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

Compensation: Varies

Number of Visits: 6

Duration: 16 weeks

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding the drug selinexor to the standard multiple myeloma treatment is more effective for individuals with newly diagnosed high-risk multiple myeloma. Selinexor stops cancer cells from growing, while the other drugs enhance the immune system's ability to fight cancer in various ways. Suitable candidates for this trial include those recently diagnosed with high-risk multiple myeloma who may have started one cycle of bortezomib-based therapy. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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

The trial does not specify if you need to stop taking your current medications, but it does prohibit the use of strong CYP3A4 inhibitors and inducers, as they can affect bortezomib exposure. Supportive care therapies like bone-directed therapies and antiviral agents are allowed.

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

Research has shown that selinexor, a drug for patients with relapsed multiple myeloma, generally has an acceptable safety profile. It has proven effective, but some patients discontinued use due to side effects. Specifically, one study found that about 16.8% of patients stopped treatment for this reason. However, real-world evidence suggests that selinexor is usually safe and tolerable.

The other drugs in the trial—daratumumab, bortezomib, and dexamethasone—have already received FDA approval for treating multiple myeloma, indicating they are generally safe for this condition. The main difference in this study is the earlier use of selinexor in the treatment process. This trial investigates whether starting selinexor earlier is safe and effective for newly diagnosed patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore innovative combinations for tackling multiple myeloma. Unlike the standard treatments, which often include bortezomib, lenalidomide, and dexamethasone, this trial introduces selinexor in one arm, which works by selectively inhibiting nuclear export. This mechanism allows it to trap tumor suppressor proteins inside the cell nucleus, potentially enhancing anti-cancer effects. Additionally, the use of daratumumab, an antibody targeting CD38 on myeloma cells, is combined with these therapies to possibly improve efficacy. These combinations aim to offer a more robust attack against multiple myeloma, potentially leading to better outcomes for patients.

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

Research has shown that the combination of selinexor, daratumumab, bortezomib, and dexamethasone (Dara-SVD), which participants in this trial may receive, could be promising for treating multiple myeloma. Although some studies did not fully achieve their main goals, they still provided encouraging results. Patients who received this combination experienced clinical benefits, and the side effects were generally manageable. Selinexor blocks a protein that helps cancer cells grow, potentially stopping or killing the cancer. Daratumumab targets a specific protein on cancer cells, aiding the immune system in attacking them. Bortezomib disrupts certain cell processes, leading to the death of cancer cells. Together, these drugs could be a strong option for patients with high-risk, newly diagnosed multiple myeloma. ^{6 7 8 9 10}

Who Is on the Research Team?

Natalia Neparidze

Principal Investigator

Yale University Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for patients with newly diagnosed high-risk multiple myeloma who may have had one cycle of bortezomib-based therapy. They should not have severe liver or kidney issues, and their immune system must be functioning at a certain level. People with HIV can join if they're on effective treatment.

Inclusion Criteria

I have been recently diagnosed with multiple myeloma.

I am mostly self-sufficient and can carry out daily activities.

I have chronic hepatitis B but it's under control with medication.

Exclusion Criteria

I do not have any uncontrolled illnesses or significant conditions.

I have recovered from side effects of previous cancer treatments, except for hair loss.

Patients receiving other investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the Dara-SVD or Dara-RVD regimen for up to 4 cycles, with each cycle lasting 28 days

16 weeks

Weekly visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

2 years

Follow-up visits at 6 months, 1 year, and 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Daratumumab
• Dexamethasone
• Selinexor

Trial Overview The study compares Dara-SVD (selinexor, daratumumab, Velcade/bortezomib, dexamethasone) to the usual Dara-RVD (daratumumab, lenalidomide, Velcade/bortezomib, dexamethasone). It's testing whether adding selinexor early in treatment offers better outcomes for those with aggressive myeloma.

How Is the Trial Designed?

Group I: Arm I (Dara-SVD) Experimental Treatment 10 Interventions

Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, \& 22 for cycles 1-2, then days 1 \& 15 for cycles 3-4, and selinexor PO, bortezomib SC, and dexamethasone PO on days 1, 8, 15, \& 22 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET, MRI, or CT, and bone marrow aspiration and biopsy, and collection of blood and urine samples throughout the study.

Group II: Arm II (Dara-RVD) Active Control 10 Interventions

Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, \& 22 for cycles 1-2, then days 1 \& 15 for cycles 3-4, lenalidomide PO QD on days 1-21 of each cycle, and bortezomib SC and dexamethasone PO on days 1, 8, 15, \& 22 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PET, MRI, or CT, and bone marrow aspiration and biopsy, and collection of blood and urine samples throughout the study.

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

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

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]

Selinexor is an oral medication that targets exportin-1 (XPO1), which is overexpressed in multiple myeloma, and has shown significant anti-myeloma effects in preclinical studies, both alone and in combination with other treatments.

Selinexor-based therapies have been approved for treating relapsed/refractory multiple myeloma, including specific combinations like selinexor-dexamethasone for advanced cases, demonstrating its efficacy in patients who have undergone multiple prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor: Targeting a novel pathway in multiple myeloma. Mo, CC., Yee, AJ., Midha, S., 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, 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 study of 34 patients with relapsed refractory multiple myeloma, the combination of selinexor, daratumumab, and dexamethasone showed a promising overall response rate of 73% and a median progression-free survival of 12.5 months in patients who had not previously received daratumumab.

The maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for selinexor was determined to be 100 mg once weekly, with common side effects including thrombocytopenia and nausea, indicating that the treatment regimen is generally well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor, daratumumab, and dexamethasone in patients with relapsed or refractory multiple myeloma. Gasparetto, C., Lentzsch, S., Schiller, G., 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, when combined with low-dose bortezomib and dexamethasone, showed a 63% overall response rate in treating relapsed or refractory multiple myeloma, with particularly high efficacy in patients not previously resistant to proteasome inhibitors (84% response rate).

The treatment was generally well-tolerated, with the most common severe side effects being thrombocytopenia (45%) and neutropenia (24%), while the recommended phase 2 dose was established as selinexor 100 mg once weekly, bortezomib 1.3 mg/m2 once weekly, and dexamethasone 40 mg once weekly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma. Bahlis, NJ., Sutherland, H., White, D., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38356463/

Selinexor, daratumumab, bortezomib and dexamethasone ... In summary, although the primary endpoint of the study was not met, the combination of S-DVd showed encouraging clinical efficacy with a generally manageable ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06169215

NCT06169215 | Comparing the Combination of Selinexor- ... This phase II trial compares the combination of selinexor, daratumumab and hyaluronidase-fihj (daratumumab), velcade (bortezomib), and dexamethasone ...

3. haematologica.org haematologica.org/article/view/haematol.2023.284089

Selinexor, daratumumab, bortezomib and dexamethasone ... Here we present the results of a phase II clinical trial conducted by the Spanish myeloma group (GEM/PETHEMA) to investigate the efficacy and ...

4. trialx.com trialx.com/clinical-trials/listings/286553/comparing-the-combination-of-selinexor-daratumumab-velcade-dexamethasone-dara-svd-with-the-usual-treatment-dara-rvd-for-high-risk-newly-diagnosed-multiple-myeloma/?&geo_lat=41.0768&geo_lng=-73.4853&radius=10&place=Darien&user_country=United%20States

Comparing the Combination of Selinexor-Daratumumab ... This phase II trial compares the combination of selinexor, daratumumab, Velcade (bortezomib), and dexamethasone (Dara-SVD) to the usual ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT297331

Selinexor, daratumumab, and dexamethasone in patients ... Single agent daratumumab has demonstrated an ORR of 29% in MM reftactory to proteasome inhibitors (PIs)/immunomodulatory drug (IMiDs). We evaluated the safety, ...

6. 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.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38537395/

Efficacy and safety of selinexor for patients with relapsed ... Conclusion: Selinexor led to significant positive responses with an acceptable safety profile in RRMM patients, despite higher rates of safety- ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0147027224000175

Efficacy and safety of selinexor for patients with relapsed ... Due to safety reasons, selinexor caused significant increase in discontinuation rate, 16.80%. Subgroup analyses demonstrated higher efficacy with selinexor plus ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10429786/

PB2106: REAL-WORLD SAFETY AND EFFECTIVENESS ... These results from a real-world cohort suggest selinexor regimens are generally tolerable, safe and effective in pts with RRMM and HD-dependent RI.

10. 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 ( ...