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

Sponsor

Karyopharm Therapeutics Inc (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT02628704

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Selinexor Drug: Placebo (for selinexor) Drug: carfilzomib Drug: Dexamethasone	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2015

Anticipated Primary Completion Date :

Jun 1, 2017

Anticipated Study Completion Date :

Jun 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Selinexor The fixed dose of selinexor is 60 mg (three 20 mg tablets) Other Names: KCP-330 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. Other Names: Kyprolis 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.
Placebo Comparator: 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.	Drug: Placebo (for selinexor) sugar tablet manufactured to mimic selinexor tablet 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. Other Names: Kyprolis 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.

Arm

Intervention/Treatment

Experimental: 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.

Drug: Selinexor

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

Other Names:

KCP-330

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.

Other Names:

Kyprolis

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.

Placebo Comparator: 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.

Drug: Placebo (for selinexor)

sugar tablet manufactured to mimic selinexor tablet

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.

Other Names:

Kyprolis

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.

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.