A Phase 1/3 Study to Evaluate Efficacy and Safety of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Ruxolitinib in Treatment-naïve Patients With Myelofibrosis
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 353
- 试验地点
- 328
- 主要终点
- Phase 3: Proportion of Participants with Spleen Volume Reduction (SVR) of Greater than or Equal to (>=) 35 Percent (%) (SVR35) at Week 24 Measured by the Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) Scan
研究概览
简要总结
This is a global, multicenter, 2-part study to evaluate the efficacy and safety of selinexor plus ruxolitinib in JAK inhibitor (JAKi) treatment-naïve myelofibrosis (MF) participants. The study will be conducted in two phases: Phase 1 (open-label) and Phase 3 (double-blind). Phase 1 (enrollment completed) was an open-label evaluation of the safety and recommended Phase 2 dose (RP2D) of selinexor in combination with ruxolitinib and included a dose escalation using a standard 3+3 design (Phase 1a) and a dose expansion part (Phase 1b). Phase 3 (ongoing), double-blind, placebo-controlled part of the study comparing the efficacy and safety of combination therapy of selinexor + ruxolitinib with combination of placebo + ruxolitinib.
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
- Double (Participant, 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
- •Aged ≥ 18 years
- •A diagnosis of primary MF or post-essential thrombocythemia (ET) or postpolycythemia- vera (PV) MF.
- •Active symptoms of MF as determined by presence of at least 2 symptoms using the Myelofibrosis Symptom Assessment Form (MFSAF) V4.
- •Participants with international prognostic scoring system (DIPSS) risk category of intermediate-1, or intermediate-2, or high-risk.
- •Measurable splenomegaly during the screening period as demonstrated by spleen volume of greater than or equal to (>=) 450 cubic centimeter (cm^3) .
- •Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (<=) 2.
排除标准
- •More than 10% blasts in peripheral blood or bone marrow (accelerated or blast phase).
- •Previous treatment with JAK inhibitors for MF.
- •Previous treatment with selinexor or other XPO1 inhibitors.
研究组 & 干预措施
Phase 3: Placebo + Ruxolitinib BID
Participants with MF will receive a matching placebo of selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with a starting dose of 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.
干预措施: Placebo (Other)
Phase 1a: Cohort 1: Selinexor 40 mg + Ruxolitinib BID
Participants with MF will receive a dose of 40 milligrams (mg) selinexor oral tablets once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib twice a day (BID) based on the participants baseline platelet count.
干预措施: Selinexor (Drug)
Phase 1a: Cohort 2: Selinexor 60 mg + Ruxolitinib BID
Participants with MF will receive a dose of 60 mg selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.
干预措施: Ruxolitinib (Drug)
Phase 1a: Cohort 1: Selinexor 40 mg + Ruxolitinib BID
Participants with MF will receive a dose of 40 milligrams (mg) selinexor oral tablets once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib twice a day (BID) based on the participants baseline platelet count.
干预措施: Ruxolitinib (Drug)
Phase 1a: Cohort 2: Selinexor 60 mg + Ruxolitinib BID
Participants with MF will receive a dose of 60 mg selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.
干预措施: Selinexor (Drug)
Phase 1b: Selinexor and Ruxolitinib BID
Participants with MF will receive a dose of 40 or 60 mg selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.
干预措施: Selinexor (Drug)
Phase 1b: Selinexor and Ruxolitinib BID
Participants with MF will receive a dose of 40 or 60 mg selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.
干预措施: Ruxolitinib (Drug)
Phase 3: Selinexor 60 mg + Ruxolitinib BID
Participants with MF will receive a fixed starting dose of 60 mg selinexor (RD) oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with a starting dose of 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.
干预措施: Selinexor (Drug)
Phase 3: Selinexor 60 mg + Ruxolitinib BID
Participants with MF will receive a fixed starting dose of 60 mg selinexor (RD) oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with a starting dose of 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.
干预措施: Ruxolitinib (Drug)
Phase 3: Placebo + Ruxolitinib BID
Participants with MF will receive a matching placebo of selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle in combination with a starting dose of 15 or 20 mg ruxolitinib BID based on the participants baseline platelet count.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Phase 3: Proportion of Participants with Spleen Volume Reduction (SVR) of Greater than or Equal to (>=) 35 Percent (%) (SVR35) at Week 24 Measured by the Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) Scan
时间窗: At Week 24
Phase 3: Absolute mean change in TSS (Abs-TSS) from baseline to Week 24 as measured by the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0
时间窗: At Week 24
Phase 1: Maximum Tolerated Dose (MTD)
时间窗: Approximately within the first cycle (28 days) of therapy
Phase 1: Recommended Phase 2 Dose (RP2D)
时间窗: Approximately within the first cycle (28 days) of therapy
Phase 1: Number of Participants With Adverse Events (AEs) by Occurrence, Nature, and Severity
时间窗: From start of drug administration up to 30 days after last dose of study treatment (approximately 48 months)
次要结局
- Phase 3: Overall survival (OS)(From Baseline up to EoS (approximately 48 months))
- Phase 3: Progression-free survival (PFS)(Time from randomization until disease progression or death, whichever occurs first (approximately 48 months))