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

NCT ID: NCT02628704

Last Updated: 2023-01-26

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2018-06-30

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

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Selinexor, carfilzomib and 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.

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

The fixed dose of selinexor is 60 mg (three 20 mg tablets)

carfilzomib

Intervention Type: DRUG

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.

Dexamethasone

Intervention Type: DRUG

Fixed oral dose of 20 mg will be given twice weekly (Days 1, 2, 8, 9, 15, 16, 22 and 23) in each cycle.

Placebo, carfilzomib and 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.

Group Type: PLACEBO_COMPARATOR

Placebo (for selinexor)

Intervention Type: DRUG

sugar tablet manufactured to mimic selinexor tablet

carfilzomib

Intervention Type: DRUG

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.

Dexamethasone

Intervention Type: DRUG

Fixed oral dose of 20 mg will be given twice weekly (Days 1, 2, 8, 9, 15, 16, 22 and 23) in each cycle.

Interventions

Selinexor

The fixed dose of selinexor is 60 mg (three 20 mg tablets)

Intervention Type: DRUG

Placebo (for selinexor)

sugar tablet manufactured to mimic selinexor tablet

Intervention Type: DRUG

carfilzomib

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.

Intervention Type: DRUG

Dexamethasone

Fixed oral dose of 20 mg will be given twice weekly (Days 1, 2, 8, 9, 15, 16, 22 and 23) in each cycle.

Intervention Type: DRUG

Other Intervention Names

KCP-330; Kyprolis

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

James R. Berenson MD, Inc

West Hollywood, California, United States

Waverly Hematology

Cary, North Carolina, United States

Countries

United States

Other Identifiers

KCP-330-015

Identifier Type: -

Identifier Source: org_study_id