Selinexor + Venetoclax + Dexamethasone for Multiple Myeloma

(SELVEDge Trial)

Recruiting at 2 trial locations

Overseen By Dickran Kazandjian, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Miami

Must not be taking: Selinexor, SINE compounds

Disqualifiers: Uncontrolled hypertension, Active infection, Cardiovascular issues, 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: Unknown

Duration: Up to 10 months

33 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research is to determine whether the combination of selinexor, venetoclax, and dexamethasone therapy can increase anti-cancer effects in patients with translocation 11;14-positive (t(11;14)), relapsed/refractory myeloma (RRMM).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

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

Research shows that Selinexor, when combined with Dexamethasone, has been effective in treating multiple myeloma that is resistant to other treatments. Additionally, the combination of Venetoclax and Selinexor has shown promise in patients with a specific genetic marker (t(11;14)) in multiple myeloma, suggesting potential effectiveness of this drug combination. ^{1 2 3 4 5}

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

The combination of Selinexor and Venetoclax has been reported as safe in a small group of patients with a specific type of multiple myeloma, although Venetoclax lacks FDA approval for multiple myeloma due to potential safety concerns. Selinexor, when combined with Dexamethasone, has a well-known safety profile with common side effects like low blood cell counts, fatigue, nausea, and weight loss, which need to be managed carefully. ^{2 4 5 6 7}

What makes the drug combination of Selinexor, Venetoclax, and Dexamethasone unique for treating multiple myeloma?

This drug combination is unique because it includes Selinexor, a first-in-class inhibitor that blocks exportin-1, helping to retain tumor suppressor proteins in the cell nucleus, and Venetoclax, which induces cancer cell death. This combination has shown promise, especially in patients with a specific genetic marker (t(11;14)), and offers a novel approach for those who have not responded to other treatments. ^{2 4 5 6 8}

Research Team

Dickran Kazandjian, MD

Principal Investigator

University of Miami

Eligibility Criteria

Adults diagnosed with relapsed/refractory multiple myeloma, specifically with t(11;14) translocation. Participants must have tried at least two prior therapies including IMiDs, proteasome inhibitors, and anti-CD38 monoclonal antibodies. They should not be pregnant or breastfeeding and must agree to use effective contraception. Excluded are those with uncontrolled infections, certain heart conditions, gastrointestinal issues affecting medication absorption, or any condition that could interfere with the study.

Inclusion Criteria

My recent tests show my organs are working well.

I am 18 years old or older.

I can take care of myself but may not be able to do heavy physical work.

Exclusion Criteria

I do not have any health conditions that could affect the study.

I do not have an active infection needing IV drugs within the last week.

I do not have severe heart problems or a recent heart attack.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive XVenD combination therapy of Selinexor, Venetoclax, and Dexamethasone orally during each 28-day cycle

Up to 10 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• Dexamethasone
• Selinexor
• Venetoclax

Trial Overview The trial is testing a combination of three drugs: Selinexor, Venetoclax, and Dexamethasone (XVenD), in patients who have a specific genetic feature in their cancer cells (t(11;14)) and whose disease has returned after treatment or did not respond to previous treatments.

Participant Groups

Group I: XVenD Group Experimental Treatment 3 Interventions

Participants will receive XVenD combination therapy of Selinexor (X), Venetoclax (Ven) and Dexamethasone (D) orally during each 28-day cycle. Doses will be administered as follows: * Cycle 1 Days 1 to 7: * Venetoclax 400 mg orally (PO), Days 1-7 * Dexamethasone 40 mg PO, Day 1 * Cycle 1 Days 8 to 28: * Venetoclax 800 mg PO, Days 8-28 * Dexamethasone 40 mg PO, Days 8, 15, and 22 * Cycles 2 to 4: * Selinexor 80 mg PO, Days 1, 8, 15, and 22 * Venetoclax 800 mg PO, Days 1-28 * Dexamethasone 40 mg PO, Days 1, 8, 15, and 22 * Cycle 5 and beyond: * Selinexor 80 mg PO, Days 1, 8, 15, and 22 * Venetoclax 800 mg PO, Days 1-28 * Dexamethasone 20 mg PO, Days 1, 8, 15, and 22 Selinexor dose will be reduced to 60 mg for remaining participants if after the first 6 participants complete the first cycle and 2 or more out of these first 6 participants experience dose-limiting toxicities (DLTs).

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?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

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

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, 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 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]

In a study involving four patients with multiple myeloma bearing the t(11;14) translocation, the combination of venetoclax and selinexor was found to be safe and led to a positive disease response.

The combination therapy was synergistic in laboratory tests, effectively reducing Cyclin D1 levels, which are linked to the t(11;14) genetic alteration, suggesting that this combination could be a promising treatment strategy for patients with this specific genetic profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination venetoclax and selinexor effective in relapsed refractory multiple myeloma with translocation t(11;14). Nguyen, N., Chaudhry, S., Totiger, TM., et al.[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 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 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]

References

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

Selinexor for the treatment of multiple myeloma. [2023]

2. France pubmed.ncbi.nlm.nih.gov

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

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

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

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Combination venetoclax and selinexor effective in relapsed refractory multiple myeloma with translocation t(11;14). [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 in Patients from Argentina with Multiple Myeloma Treated with Multiple Prior Therapies: A Case Series. [2022]

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]