Clinical trial NCT02628704: Selinexor, Carfilzomib, and Dexamethasone Versus Placebo, Carfilzomib, and Dexamethasone in Multiple Myeloma
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 type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Karyopharm
selinexor
KPT-330
multiple myeloma
SCORE
Lead sponsor: Karyopharm Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2015-12-11
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 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 outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Assessed from the date of first dose of blinded study treatment until the date that PD assessed up to 24 months
Other outcomes:
Locations:
city: West Hollywood
country: United States
facility: James R. Berenson MD, Inc
state: California
city: Cary
country: United States
facility: Waverly Hematology
state: North Carolina
Study officials:
References: