A Randomized, Double Blind, Placebo-controlled, Multicenter, Phase III Study Investigating the Efficacy and Safety of Ruxolitinib in Early Myelofibrosis Patients With High Molecular Risk Mutations
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- Progression Free Survival (PFS-1)
研究概览
简要总结
Myelofibrosis patients with high molecular risk mutations have an intrinsically aggressive disease with increased risk of leukemic transformation and reduced overall survival. As there are no therapies currently established in the subset of high molecular risk patients with early myelofibrosis, the study aimed to evaluate ruxolitinib in this patient population.
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
- •Confirmed diagnosis of MF with bone marrow fibrosis of at least Grade 1; irrespective of JAK2 mutational status
- •Patients with at least one mutation in one of the five HMR genes (ASXL1, EZH2, SRSF2 and IDH1/2)
- •Patients with non-palpable spleen or spleen palpable ≤ 5 cm from the left costal margin to the point of greatest splenic protrusion
- •Patients with MF-7 score of ≤ 15, with each individual symptom score of ≤ 3
排除标准
- •Patients with prior treatment with ruxolitinib or other JAK inhibitors.
研究组 & 干预措施
Ruxolitinib
Two tablets of ruxolitinib 5 mg were administered orally twice per day.
干预措施: Ruxolitinib (Drug)
Ruxolitinib Placebo
Two tablets of 5mg placebo were administered orally twice per day.
干预措施: Ruxolitinib Placebo (Drug)
结局指标
主要结局
Progression Free Survival (PFS-1)
时间窗: From randomization till disease progression (estimated to be assessed up 48 months)
Progression free survival (PFS-1) from date of randomization until the occurrence of any of the criteria for disease progression: * Progressive splenomegaly * Circulating peripheral blast counts \> 10% * Leukemic transformation * Hb \< 10g/dl with absolute decrease of at least 3 g/dl from baseline * White blood cell (WBC) counts \> 25 x 103/ μL * MF-7 score ≥ 30 * Death from any cause
次要结局
- Time to Primary Progression (TTP)(From randomization till progression (estimated to be assessed up to 48 months))
- Overall Survival(Time from randomization to date of death due to any cause (estimated to be assessed up to 48 months).)
- Percentage Change in Spleen Volume From Baseline(From baseline and assessed on 12 week intervals until end of treatment (EOT))
- Percentage Change in Symptoms From Baseline Using MF-7(From Baseline and assessed every 4 weeks until end of treatment)
- Number of Participants With Specific Subscale Scores (From Baseline) Using EQ-5D(From Baseline and assessed every 4 weeks until end of treatment)
- Plasma Ruxolitinib Concentrations(Week 12, Wk 48)
- Progression Free Survival (PFS-2)(From date of randomization until second disease progression or death, whichever comes first (estimated to be assessed up to 72 months))
- Quality-adjusted Life Years From Baseline(Change from Baseline compared with scheduled study visits at the following intervals every 4 weeks up to week 24, every 8 weeks up to Week 48, every 12 weeks past Wk 48 until End of treatment and 30 day follow up visit)
- Time to First Progressive Splenomegaly (TTPS)(From randomization until earliest time to progressive splenomegaly (estimated to be assessed up to 48 months))
- Time to First Symptomatic Progression (TTSP)(From randomization until symptomatic progression (MF-7)(estimated to be assessed up to 48 months))