SPd vs EloPd Chemotherapy for Multiple Myeloma
Recruiting in Palo Alto (17 mi)
+100 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
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
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
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.
12345What 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.
13567Is 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.
89101112Eligibility 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.
+15 more
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
+17 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Selinexor, pomalidomide and dexamethasone (SPd)Experimental Treatment3 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 Control3 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
California Cancer Associates for Research and ExcellenceEncinitas, CA
Baptist Health South FloridaDelray Beach, FL
Millennium Oncology Research ClinicHollywood, FL
Our Lady of the Lake HospitalBaton Rouge, LA
More Trial Locations
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Who Is Running the Clinical Trial?
Stichting European Myeloma NetworkLead Sponsor
European Myeloma NetworkLead Sponsor
Karyopharm Therapeutics IncIndustry Sponsor
References
Targeting Nuclear Export Proteins in Multiple Myeloma Therapy. [2022]Multiple myeloma (MM) is an incurable malignancy of plasma cells with a clinical course characterized by multiple relapses and treatment refractoriness. While recent treatment advancements have extended overall survival (OS), refractory MM has a poor prognosis, with a median OS of between 4 and 6 months. Nuclear export inhibition, specifically inhibition of CRM1/XPO1, is an emerging novel treatment modality that has shown promise in treatment-refractory MM. Initially discovered in yeast in 1983, early clinical applications were met with significant toxicities that limited their utility. The creation of small molecule inhibitors of nuclear export (SINE) has improved on toxicity limitations and has led to investigation in a number of malignancies at the preclinical and clinical stages. Preclinical studies of SINEs in MM have shown that these molecules are cytotoxic to myeloma cells, play a role in therapy resensitization, and suggest a role in limiting bone disease progression. In July 2019, selinexor became the first nuclear export inhibitor approved for use in relapsed/refractory MM based on the STORM trial. As of May 2020, there were eight ongoing trials combining selinexor with standard treatment regimens in relapsed/refractory MM. Eltanexor, a second-generation SINE, is also under investigation and has shown preliminary signs of efficacy in an early clinical trial while potentially having an improved toxicity profile compared with selinexor. Results in ongoing trials will help further define the role of SINEs in MM.
Clinical Implications of Targeting XPO1-mediated Nuclear Export in Multiple Myeloma. [2023]Multiple myeloma (MM) is a malignancy of plasma cells that is typically chronic, and relapse is common. Current therapeutic strategies include combination and sequential treatments with corticosteroids, alkylating agents, proteasomal inhibitors, immunomodulators, and monoclonal antibodies. These drugs prolong survival but ultimately become ineffective. Exportin 1 (XPO1), a nuclear export protein, is overexpressed in MM cells, and knockdown studies have suggested that XPO1 is essential for MM cell survival. Selective inhibitor of nuclear export (SINE) compounds are novel, orally bioavailable class of agents that specifically inhibit XPO1. Selinexor (KPT-330) is the first-in-human SINE compound. Early phase clinical trials have established the safety profile of this agent and have shown promising efficacy in combination with low-dose dexamethasone and other anti-MM agents. The combination of selinexor and dexamethasone has demonstrated activity in "penta-refractory" MM, (ie, MM refractory to the 5 most active anti-MM agents currently used in treatment). We have reviewed the available data on the molecular implications of XPO1 inhibition in MM. We also reviewed the pertinent early phase clinical data with SINE compounds and discuss management strategies for common toxicities encountered with use of selinexor.
Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma. [2023]Selinexor, a selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1) and forces nuclear accumulation and activation of tumor suppressor proteins, inhibits nuclear factor κB, and reduces oncoprotein messenger RNA translation, is a potential novel treatment for myeloma that is refractory to current therapeutic options.
Selinexor for the treatment of multiple myeloma. [2023]Introduction: Despite unprecedented advances in the treatment of multiple myeloma (MM), almost all patients develop a disease that is resistant to the five most commonly used and active anti-MM agents. The prognosis for this patient population is particularly poor resulting in an unmet need for additional therapeutic options. Exportin-1 (XPO-1) is a major nuclear export protein of macromolecular cargo frequently overexpressed in MM. Selinexor is a first-in-class, oral Selective-Inhibitor-of-Nuclear-Export (SINE) compound that impedes XPO-1. Based on results of the STORM-trial, selinexor in combination with dexamethasone was granted accelerated FDA approval for patients with penta-refractory MM in July 2019.Areas covered: This article summarizes our up-to-date knowledge on the pathophysiologic role of XPO-1 in MM. Furthermore, it reviews the most recent clinical data on selinexor in combination with dexamethasone and other anti-MM agents; and discusses its safety profile, management strategies; and potential future developments.Expert opinion: Selinexor represents a next-generation-novel agent with an innovative mechanism of action that marks a significant advance in the treatment of heavily pretreated MM patients. Ongoing studies investigate its therapeutic potential also in earlier lines of therapy. Additional data is needed to confirm that selinexor and other SINE compounds are a valuable addition to our current therapeutic armamentarium.
Selinexor in Patients from Argentina with Multiple Myeloma Treated with Multiple Prior Therapies: A Case Series. [2022]BACKGROUND Numerous treatment options are available for patients with multiple myeloma (MM). Because of the course of the disease, most patients will experience serial relapse or the MM will become refractory to most of these treatments, leaving patients with few or no treatment options over time. Selinexor, a treatment with a novel mechanism of action, is an oral selective inhibitor of nuclear export (SINE) compound that blocks exportin 1, the major nuclear exporter of tumor suppressor proteins. CASE REPORT In this case series, we report on treatment with the weekly oral administration of selinexor combined with bortezomib and dexamethasone (XVd) in 3 patients from Argentina who were heavily treated (5-7 prior therapies) for MM that relapsed or was refractory to each previous treatment. Two patients had the high-risk cytogenetic abnormality del(17p). All 3 patients experienced efficacy with XVd reaching a best response of partial response or very good partial response. These responses were consistent with those of patients from the BOSTON study who were treated with XVd but were less heavily pretreated (1-3 prior therapies) and had a shorter median time since diagnosis of MM (7 years vs 3.7 years). The 3 patients experienced adverse events (AEs) that included nausea, thrombocytopenia, asthenia, and fatigue, which were similar to the most commonly reported AEs associated with selinexor treatment. CONCLUSIONS With its oral administration, novel mechanism of action, and responses in heavily pretreated patients, selinexor may help to address an important clinical need in the treatment of patients with relapsed/refractory MM.
Targeting Nuclear Export Proteins in Multiple Myeloma Therapy. [2022]Nuclear export proteins such as exportin-1 (XPO1) transport tumor-suppressor proteins and other growth-regulatory proteins from the nucleus to the cytoplasm. Overexpression of XPO1 has been observed in several cancers and correlates with shorter event-free and overall survival in multiple myeloma. Selinexor was developed as an oral first-in-class selective inhibitor of nuclear export (SINE) that inhibits XPO1. Preclinical studies in tumor cell lines and mouse models have demonstrated the efficacy of selinexor both as a single agent and in various combinations with known active antimyeloma agents. Results from the pivotal phase II STORM trial led to the US FDA approval of selinexor with dexamethasone in penta-refractory myeloma. Because of the feasibility of combining selinexor with other active antimyeloma agents, the multiarm STOMP trial was initiated and is ongoing, with impressive response rates reported in some of the combination arms thus far. The registrational phase III BOSTON trial demonstrated the superiority of selinexor in combination with bortezomib and dexamethasone as compared with bortezomib and dexamethasone in patients with relapsed refractory multiple myeloma (RRMM) who have received one to three prior anti-MM regimens. The toxicity profile of selinexor is well established and predictable and may be significant unless managed aggressively and preemptively. The most common side effects are thrombocytopenia, anemia, neutropenia, fatigue, nausea, anorexia, and weight loss. Hyponatremia and cataracts seem to be class effects. Other SINE compounds are now being studied in efforts to discover agents that will potentially be better tolerated. Eltanexor is an investigational SINE compound that has shown a more positive toxicity profile in preclinical studies, with reduced central nervous system penetration and gastrointestinal side effects, and is now undergoing clinical investigation. These and other trials will further clarify the role of these innovative agents in the therapeutic advancement of RRMM.
Selinexor therapy for multiple myeloma and non-Hodgkin lymphomas. [2023]In this review we highlight the most recent studies furthering the clinical development of selinexor, a novel exportin-1 inhibitor, for the treatment of multiple myeloma and non-Hodgkin lymphomas.
Elotuzumab Plus Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Final Overall Survival Analysis From the Randomized Phase II ELOQUENT-3 Trial. [2023]In the phase II ELOQUENT-3 trial (ClinicalTrials.gov identifier: NCT02654132), elotuzumab combined with pomalidomide/dexamethasone (EPd) significantly improved progression-free survival (PFS) versus pomalidomide/dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma (RRMM) previously treated with lenalidomide and a proteasome inhibitor (PI). Here, we present the final overall survival (OS) results.
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]In the ELOQUENT-3 trial, the combination of elotuzumab, pomalidomide and dexamethasone (EloPd) proved a superior clinical benefit over Pd with a manageable toxicity profile, leading to its approval in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI). We report here a real-world experience of 200 RRMMs treated with EloPd in 35 Italian centers outside of clinical trials. In our dataset, the median number of prior lines of therapy was 2, with 51% of cases undergoing autologous stem cell transplant (ASCT) and 73% exposed to daratumumab. After a median follow-up of 9 months, 126 patients stopped EloPd, most of them (88.9%) because of disease progression. The overall response rate (ORR) was 55.4%, in line with the pivotal trial results. Regarding adverse events, our cohort experienced a toxicity profile similar to the ELOQUENT-3 trial, with no significant differences between younger (
Elotuzumab plus lenalidomide and dexamethasone for newly diagnosed multiple myeloma: a randomized, open-label, phase 2 study in Japan. [2020]Novel therapies are needed for patients with newly diagnosed multiple myeloma (NDMM). Elotuzumab plus lenalidomide and dexamethasone (ELd) is approved for the treatment of relapsed/refractory multiple myeloma (RRMM). This phase 2 study in Japan evaluated ELd vs lenalidomide and dexamethasone (Ld) in patients with NDMM who were ineligible for stem cell transplantation. Elotuzumab infusion was accelerated to 5 mL/min by dose 3, cycle 1, allowing most subsequent infusions to be completed within 1 h. The primary endpoint was overall response rate (ORR) in the ELd arm. Secondary endpoints were the difference in ORR between treatments, and progression-free survival (PFS). Patients were randomized to ELd (n = 40) or Ld (n = 42); median number of treatment cycles was 13 (ELd) and 12 (Ld). In the ELd arm, ORR was 88% [70% confidence interval (CI) 80-93]. The estimated difference in ORR between treatments was 13% (95% CI - 4, 30) in favor of ELd. Progression-free survival data were immature. Safety was consistent with previous findings of ELd in Japanese patients with RRMM. No infusion reactions occurred at the maximum rate of 5 mL/min, which was used in 89% of elotuzumab infusions. ELd may be an effective, well-tolerated frontline treatment for patients with NDMM ineligible for stem cell transplantation.
Population pharmacokinetic and exposure-response analyses of elotuzumab plus pomalidomide and dexamethasone for relapsed and refractory multiple myeloma. [2022]Elotuzumab plus pomalidomide/dexamethasone (E-Pd) demonstrated efficacy and safety in relapsed and refractory multiple myeloma (RRMM). The clinical pharmacology of elotuzumab [± lenalidomide/dexamethasone (Ld)] was characterized previously. These analyses describe elotuzumab population pharmacokinetics (PPK), the effect of Pd, and assess elotuzumab exposure-response relationships for efficacy and safety in patients with RRMM.
Elotuzumab: A Review in Relapsed and/or Refractory Multiple Myeloma. [2019]Intravenous elotuzumab (Empliciti™), a monoclonal antibody targeting the signalling lymphocytic activation molecule F7 (SLAMF7) glycoprotein, is approved for use in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma in previously-treated adult patients. In the pivotal, multinational, phase III ELOQUENT-2 trial in adults with relapsed and/or refractory multiple myeloma, elotuzumab in combination with lenalidomide and dexamethasone significantly prolonged median progression-free survival (PFS) and increased overall response rate (ORR; co-primary endpoints) compared with lenalidomide and dexamethasone alone. The clinical benefit of elotuzumab was maintained over the longer term (≤ 4 years' minimum follow-up); final overall survival data are awaited. Health-related quality of life was not negatively impacted by the addition of elotuzumab. Elotuzumab combination therapy had a generally manageable tolerability profile and the most common adverse events (AEs) of grade ≥ 3 severity were haematological (e.g. lymphocytopenia, anaemia, thrombocytopenia, neutropenia). Elotuzumab plus lenalidomide and dexamethasone extends the treatment options available for the management of relapsed and/or refractory multiple myeloma.