A Multi-Center, Phase 1/2, Open-Label Study of Selinexor (KPT- 330), Lenalidomide, and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 主要终点
- Determine maximum tolerated dose (MTD)
研究概览
简要总结
This is an open-label, randomized clinical study with two stages to assess the maximum tolerated dose (MTD), efficacy, and safety of selinexor, lenalidomide, and dexamethasone (SLd) in patients with relapsed/refractory (RR) multiple myeloma (MM). The stages are dose escalation (Phase 1) and expansion (Phase 2).
详细描述
In Phase 1 (Dose Escalation), patients will be randomized to either once-weekly (Arm A) or twice- weekly (Arm B) dosing with selinexor. Dose escalation will be performed within each arm for both lenalidomide and selinexor to determine the selinexor MTD for that arm. Each arm will be expanded until approximately 17 patients have been treated at the MTD in each arm. The Sponsor and Investigator will review the MTD, efficacy, and safety data from Phase 1 to determine which dose schedule (Arm A or B) to be used as the RP2D dose in the Expansion Phase.
In Phase 2 (Expansion), patients who had received the MTD dose that was nominated for RP2D will continue at the same dose. Patients who did not receive the RP2D for that arm will stay on their Phase 1 dose. Additional patients will be accrued, as needed, to achieve the target population size of approximately 34 patients at the RP2D.
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
- None
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
- •Histologically confirmed diagnosis, measurable disease and evidence of disease progression of MM.
- •Relapsed or refractory to the most recently received therapy. Relapsed is defined as documented evidence of PD after achieving at least SD for ≥ 1 cycle. Refractory disease is defined as ≤ 25% response (i.e., patients never achieved minimal response or better) or progression during therapy or within 60 days after completion of therapy.
- •Symptomatic MM, based on IMWG guidelines. Patients must have measurable disease.
排除标准
- •Smoldering MM.
- •Multiple myeloma that does not express M-protein or FLC (i.e., non-secretory MM is excluded), and quantitative immunoglobulin levels cannot be used instead.
- •Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
- •Active MM involving the central nervous system (CNS).
研究组 & 干预措施
A: Selinexor (1x/week), Lenalidomide, & Dexamethasone
Lenalidomide will be dosed initially at 15 mg daily, and if that dose is tolerated per dose-limiting toxicity (DLT criteria,) it will be increased to 25 mg for that arm. Selinexor will be started at 80 mg (~45 mg/m2) once weekly in combination with dexamethasone 40 mg once weekly with each dose of selinexor. If the selinexor 80 mg dose is tolerated per DLT criteria, the dose will be increased to 100 mg (~60 mg/m2) and evaluated for MTD, tolerability and efficacy.
干预措施: Selinexor (Drug)
A: Selinexor (1x/week), Lenalidomide, & Dexamethasone
Lenalidomide will be dosed initially at 15 mg daily, and if that dose is tolerated per dose-limiting toxicity (DLT criteria,) it will be increased to 25 mg for that arm. Selinexor will be started at 80 mg (~45 mg/m2) once weekly in combination with dexamethasone 40 mg once weekly with each dose of selinexor. If the selinexor 80 mg dose is tolerated per DLT criteria, the dose will be increased to 100 mg (~60 mg/m2) and evaluated for MTD, tolerability and efficacy.
干预措施: Lenalidomide (Drug)
A: Selinexor (1x/week), Lenalidomide, & Dexamethasone
Lenalidomide will be dosed initially at 15 mg daily, and if that dose is tolerated per dose-limiting toxicity (DLT criteria,) it will be increased to 25 mg for that arm. Selinexor will be started at 80 mg (~45 mg/m2) once weekly in combination with dexamethasone 40 mg once weekly with each dose of selinexor. If the selinexor 80 mg dose is tolerated per DLT criteria, the dose will be increased to 100 mg (~60 mg/m2) and evaluated for MTD, tolerability and efficacy.
干预措施: Dexamethasone (Drug)
B: Selinexor (2x/week), Lenalidomide, & Dexamethasone
Lenalidomide will be dosed initially at 15 mg daily, and if that dose is tolerated per DLT criteria, it will be increased to 25 mg for that arm. Selinexor will be started at 60 mg (~35 mg/m2) twice weekly in combination with dexamethasone 20 mg twice weekly with each dose of selinexor; dexamethasone 20 mg will also be given, without selinexor, on Days 22 and 24. If the selinexor 60 mg dose is tolerated per DLT criteria, the dose will be increased to 80 mg (~45 mg/m2) and evaluated for MTD, tolerability and efficacy.
干预措施: Selinexor (Drug)
B: Selinexor (2x/week), Lenalidomide, & Dexamethasone
Lenalidomide will be dosed initially at 15 mg daily, and if that dose is tolerated per DLT criteria, it will be increased to 25 mg for that arm. Selinexor will be started at 60 mg (~35 mg/m2) twice weekly in combination with dexamethasone 20 mg twice weekly with each dose of selinexor; dexamethasone 20 mg will also be given, without selinexor, on Days 22 and 24. If the selinexor 60 mg dose is tolerated per DLT criteria, the dose will be increased to 80 mg (~45 mg/m2) and evaluated for MTD, tolerability and efficacy.
干预措施: Lenalidomide (Drug)
B: Selinexor (2x/week), Lenalidomide, & Dexamethasone
Lenalidomide will be dosed initially at 15 mg daily, and if that dose is tolerated per DLT criteria, it will be increased to 25 mg for that arm. Selinexor will be started at 60 mg (~35 mg/m2) twice weekly in combination with dexamethasone 20 mg twice weekly with each dose of selinexor; dexamethasone 20 mg will also be given, without selinexor, on Days 22 and 24. If the selinexor 60 mg dose is tolerated per DLT criteria, the dose will be increased to 80 mg (~45 mg/m2) and evaluated for MTD, tolerability and efficacy.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Determine maximum tolerated dose (MTD)
时间窗: 12 months
Determine the maximum tolerated dose (MTD) of selinexor in the combination SLd in patients with RR MM, as determined by dose limiting toxicities (DLTs), efficacy, and safety
Overall response rate (ORR)
时间窗: 12 months
According to the International Myeloma Working Group \[IMWG\] criteria, Overall Response Rate (ORR) includes: stringent complete response \[sCR\], complete response \[CR\], very good partial response \[VGPR\], and partial response \[PR\]
次要结局
未报告次要终点