Multiple Myeloma
Conditions
Keywords
Karyopharm, selinexor, KPT-330, multiple myeloma, SCORE
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
Interventions
DRUGSelinexor
The fixed dose of selinexor is 60 mg (three 20 mg tablets)
DRUGPlacebo (for selinexor)
sugar tablet manufactured to mimic selinexor tablet
DRUGcarfilzomib
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.
DRUGDexamethasone
Fixed oral dose of 20 mg will be given twice weekly (Days 1, 2, 8, 9, 15, 16, 22 and 23) in each cycle.
Sponsors
Karyopharm Therapeutics Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
United States
Outcome results
None listed