Selinexor, Carfilzomib, and Dexamethasone Versus Placebo, Carfilzomib, and Dexamethasone in Multiple Myeloma

Study Overview
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Brief Summary
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Double-blind study will compare the efficacy and assess safety of selinexor plus carfilzomib (Kyprolis®) plus low-dose dexamethasone versus placebo plus carfilzomib plus low-dose dexamethasone in patients with relapsed/refractory multiple myeloma.

Detailed Description
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This is a Phase 2, two-arm, randomized, placebo-controlled, double-blind, multicenter study of relapsed/refractory multiple myeloma patients who have received at least two prior therapies, including a proteasome inhibitor and an IMiD. Patients who meet all the eligibility criteria will be randomized to one of two blinded treatment arms: selinexor + carfilzomib + dexamethasone placebo + carfilzomib + dexamethasone

Official Title
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Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Study of Selinexor (KPT-330), Carfilzomib, and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma Previously Treated With a Proteasome Inhibitor and an Immunomodulatory Drug

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Selinexor
* Drug: Placebo (for selinexor)
* Drug: carfilzomib
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic, histologically confirmed MM, based on IMWG guidelines. Patients must have measurable disease as defined by at least one of the following: Serum M-protein ≥ 1.0 g/dL by serum protein electrophoresis (SPEP) or for immunoglobulin (Ig) A myeloma, by quantitative IgA; or Urinary M-protein excretion at least 200 mg/24 hours; or Serum FLC ≥ 100 mg/L, provided that the serum FLC ratio is abnormal. If serum protein electrophoresis is felt to be unreliable for routine M- protein measurement, then quantitative Ig levels by nephelometry or turbidometry are acceptable. Must have received ≥ 2 prior anti-MM therapies including a proteasome inhibitor and an IMiD. The most recent proteasome inhibitor must not have been carfilzomib. Patients previously treated with carfilzomib are eligible as long as they meet the following criteria: Not received carfilzomib within 6 months (183 days) of Cycle 1 Day 1 (C1D1), and Carfilzomib was not part of their most recent therapy for the treatment of MM, and Did not discontinue carfilzomib treatment because of adverse effects. MM that is refractory to the most recent treatment regimen. Refractory is defined as ≤ 25% response to therapy, or progression during therapy, or progression on or within 60 days after completion of therapy. Exclusion Criteria: Smoldering MM. Active plasma cell leukemia. MM that does not express M-protein or serum FLC (i.e., non-secretory MM is excluded; plasmacytomas without M-protein or serum FLC are excluded). Documented active systemic amyloid light chain amyloidosis. Active MM involving the central nervous system. Active polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. Prior autologous stem cell transplantation < 1 month or allogenic stem cell transplantation < 3 months prior to C1D1. Active graft versus host disease (after allogeneic stem cell transplantation) at C1D1.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selinexor, carfilzomib and dexamethasone<br>60 mg of selinexor and and 20 mg of dexamethasone will be taken twice weekly. On days coinciding with carfilzomib administration, selinexor will be given between 30 minutes and 4 hours after the end of the carfilzomib infusion. | Drug: Selinexor<br>* The fixed dose of selinexor is 60 mg (three 20 mg tablets)<br>* Other names: KCP-330;Drug: carfilzomib<br>* Administered as an IV infusion on Days 1, 2, 8, 9, 15 and 16 of each 4-week cycle for Cycles 1-13 and then on Days 1, 2, 15, and 16 for Cycles ≥ 14.<br>* Other names: Kyprolis;Drug: Dexamethasone<br>* Fixed oral dose of 20 mg will be given twice weekly (Days 1, 2, 8, 9, 15, 16, 22 and 23) in each cycle.<br>|
| Placebo Comparator: Placebo, carfilzomib and dexamethasone<br>Placebo (for 60 mg of selinexor) and and 20 mg of dexamethasone will be taken twice weekly. On days coinciding with carfilzomib administration, Placebo (for 60 mg of selinexor) will be given between 30 minutes and 4 hours after the end of the carfilzomib infusion. | Drug: Placebo (for selinexor)<br>* sugar tablet manufactured to mimic selinexor tablet<br>Drug: carfilzomib<br>* Administered as an IV infusion on Days 1, 2, 8, 9, 15 and 16 of each 4-week cycle for Cycles 1-13 and then on Days 1, 2, 15, and 16 for Cycles ≥ 14.<br>* Other names: Kyprolis;Drug: Dexamethasone<br>* Fixed oral dose of 20 mg will be given twice weekly (Days 1, 2, 8, 9, 15, 16, 22 and 23) in each cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) |  | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) |  | Assessed from the date of first dose of blinded study treatment until the date that PD assessed up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Karyopharm, selinexor, KPT-330, multiple myeloma, SCORE