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

Phase 2

Withdrawn

• Conditions: Multiple Myeloma
• Interventions: Drug: Selinexor; Drug: Placebo (for selinexor); Drug: carfilzomib; Drug: Dexamethasone

• Registration Number: NCT02628704
• Lead Sponsor: Karyopharm Therapeutics Inc

Brief Summary

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

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

Study Timeline

• Study Start: 2015-12
• Study First Submitted: 2015-12-02
• Study First Submitted QC: 2015-12-09
• Study First Posted: 2015-12-11
• Primary Completion: 2017-06
• Study Completion: 2018-06
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-24
• Last Update Posted: 2023-01-26

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Selinexor, carfilzomib and dexamethasone	Selinexor	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.
Selinexor, carfilzomib and dexamethasone	Dexamethasone	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.
Placebo, carfilzomib and dexamethasone	Placebo (for selinexor)	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.
Selinexor, carfilzomib and dexamethasone	carfilzomib	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.
Placebo, carfilzomib and dexamethasone	carfilzomib	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.
Placebo, carfilzomib and dexamethasone	Dexamethasone	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (2)

James R. Berenson MD, Inc; 🇺🇸 West Hollywood, California, United States

Waverly Hematology; 🇺🇸 Cary, North Carolina, United States