Selinexor + Daratumumab + Carfilzomib + Dexamethasone for Multiple Myeloma

Not currently recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Academic and Community Cancer Research United

Disqualifiers: Uncontrolled hypertension, Significant cardiac disease, Hepatitis B, 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: 4

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination for multiple myeloma, a type of blood cancer that has returned or resisted earlier treatments. Researchers aim to determine if adding selinexor, a potential new drug, to carfilzomib, daratumumab, and dexamethasone is more effective than using the latter three drugs alone. This combination may inhibit cancer growth by blocking certain proteins and enhancing the immune system. Individuals whose multiple myeloma has returned after 1 to 3 previous treatments and who meet specific medical conditions might qualify for this trial. As a Phase 2 trial, this study measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important research.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had any multiple myeloma therapy within 14 days before starting the trial treatment.

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

Research shows that the combination of selinexor, carfilzomib, daratumumab, and dexamethasone is generally safe for patients with multiple myeloma, a type of blood cancer. Studies have found that selinexor, when combined with other drugs like dexamethasone, received FDA approval for certain cases of multiple myeloma, indicating its safety for humans.

Additionally, treatments based on selinexor have proven effective for patients whose disease has returned or not responded to other treatments. While some side effects may occur, as with many cancer treatments, this combination therapy has shown promise in managing the disease with a tolerable safety level. Participants should discuss potential risks and benefits with their healthcare providers before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of selinexor, daratumumab, carfilzomib, and dexamethasone for treating multiple myeloma because it brings a unique approach to tackling this cancer. Unlike standard treatments that often target a single pathway, this combination strikes multiple targets at once, potentially enhancing its effectiveness. Selinexor, in particular, introduces a novel mechanism by inhibiting the export of tumor suppressor proteins from the nucleus, which can help in controlling cancer cell growth. By combining these diverse mechanisms, this treatment could offer a more comprehensive strategy against multiple myeloma, aiming to improve patient outcomes.

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

Studies have shown that using selinexor with dexamethasone and other drugs can slow the progression of multiple myeloma, a type of blood cancer. In this trial, participants will receive a combination of selinexor, carfilzomib, daratumumab, and dexamethasone. Selinexor blocks a protein that aids cancer cell growth. When combined with carfilzomib, which kills cancer cells, and daratumumab, which prevents their spread, the treatment might be more effective. Previous patients treated with selinexor-based combinations have shown promising results, particularly those whose disease returned or did not respond to other treatments. Overall, this combination could be a strong treatment option for people with hard-to-treat multiple myeloma. ^{3 4 6 7 8}

Who Is on the Research Team?

Shebli Atrash

Principal Investigator

Academic and Community Cancer Research United

Are You a Good Fit for This Trial?

This trial is for adults with high-risk multiple myeloma that has returned or hasn't responded to treatment, having had 1-3 prior therapies. Participants must have adequate organ function and agree to use effective contraception. Those who've had certain toxic reactions to similar drugs, uncontrolled diseases, or specific infections can't join.

Inclusion Criteria

I have had 1 to 3 treatments for my condition before.

I signed the consent form less than 28 days ago.

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

Exclusion Criteria

You have tested positive for hepatitis C.

Receiving any other investigational agent considered as a treatment for the primary neoplasm

I have not taken daratumumab in the last 24 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive carfilzomib, daratumumab, dexamethasone, and selinexor in 28-day cycles

Up to 5 years

Multiple visits per cycle, including days 1, 8, 15, and 22

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Every 3 months until progression, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Daratumumab
• Dexamethasone
• Selinexor

Trial Overview The study tests selinexor combined with carfilzomib, daratumumab, and dexamethasone in patients with recurrent or refractory multiple myeloma. It aims to see if this mix works better than the standard trio of drugs alone by blocking proteins that cancer cells need.

How Is the Trial Designed?

Group I: Treatment (carfilzomib, daratumumab, dexamethasone, selinexor) Experimental Treatment 5 Interventions

Patients receive carfilzomib IV over 30 minutes on days 1, 8, and 15 and daratumumab IV on days 1 and 2 of cycle 1 then days 8, 15, and 22 of cycle 1, then, days 1, 8, 15, and 22 of cycle 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles. Patients also receive dexamethasone PO on days 1, 8 15, and 22, and selinexor PO on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Kyprolis for:

• Multiple myeloma

Approved in European Union as Kyprolis for:

• Multiple myeloma

Approved in Canada as Kyprolis for:

• Multiple myeloma

Approved in Japan as Kyprolis for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Academic and Community Cancer Research United

Lead Sponsor

Trials

54

Recruited

4,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 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, 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]

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 combination of selinexor, carfilzomib, and dexamethasone (XKd) demonstrated a high overall response rate of 78% in patients with relapsed refractory multiple myeloma, indicating strong efficacy.

The treatment was well-tolerated, with manageable side effects such as thrombocytopenia and nausea, and the maximum-tolerated dose was established as selinexor 80 mg, carfilzomib 56 mg/m2, and dexamethasone 40 mg, all administered weekly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients. Gasparetto, C., Schiller, GJ., Tuchman, SA., et al.[2022]

In a phase 3 study involving 466 patients with relapsed or refractory multiple myeloma, the combination of carfilzomib, dexamethasone, and daratumumab (KdD) significantly improved progression-free survival compared to carfilzomib and dexamethasone alone (Kd), with a hazard ratio of 0.63, indicating a 37% reduction in the risk of disease progression.

Despite a higher incidence of grade 3 or higher adverse events in the KdD group (82%) compared to the Kd group (74%), the overall safety profile was considered favorable, with similar rates of treatment discontinuation due to adverse events in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Dimopoulos, M., Quach, H., Mateos, MV., et al.[2020]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02343042

Study Details | NCT02343042 | Selinexor and Backbone ... This study will independently assess the efficacy and safety of 11 combination therapies in 12 arms, in dose-escalation/-evaluation and expansion phases.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11215366/

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

3. sciencedirect.com sciencedirect.com/science/article/pii/S2152265023001842

Selinexor-Based Triplet Regimens in Patients With Multiple ... Selinexor-based regimens may offer effective and well-tolerated therapy to patients with relapsed and/or refractory MM who had disease previously exposed or ...

4. myeloma.org myeloma.org/videos/once-weekly-selinexor-carfilzomib-dexamethasone-xkd-heavily-pretreated-multiple-myeloma

Selinexor, carfilzomib and dex | Itn'l Myeloma Fndtn These data support further investigation of XKd in patients with previously treated multiple myeloma including those previously treated with ...

5. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK603404/

Selinexor (Xpovio) - NCBI Bookshelf Evidence from a clinical trial demonstrated that Xpovio delayed progression of multiple myeloma when added to bortezomib and dexamethasone. Xpovio meets ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04661137

NCT04661137 | A Study of Selinexor, in Combination With ... Results of the Pivotal STORM Study (Part 2) in Penta-Refractory Multiple Myeloma (MM): Deep and Durable Responses with Oral Selinexor Plus low dose ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-02748

Selinexor in Combination with Carfilzomib, Daratumumab ... Giving selinexor with carfilzomib, daratumumab or pomalidomide, and dexamethasone may kill more cancer cells in patients with multiple myeloma that is relapsing ...

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

Selinexor, daratumumab, and dexamethasone in patients ... Selinexor in combination with low dose dexamethasone (Sel-dex) was approved by the FDA, based on data from the STORM study, wherein Sel-dex induced an overall ...