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
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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 C1D
- •Active graft versus host disease (after allogeneic stem cell transplantation) at C1D1.
研究组 & 干预措施
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.
干预措施: Selinexor (Drug)
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.
干预措施: carfilzomib (Drug)
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.
干预措施: Dexamethasone (Drug)
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.
干预措施: Placebo (for selinexor) (Drug)
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.
干预措施: carfilzomib (Drug)
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.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: 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
次要结局
- 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)