A Phase Ib, Open-label, Dose-finding Study of the JAK Inhibitor INC424 Tablets Administered Orally to Patients With Primary Myelofibrosis (PMF), Post-polycythemia Veramyelofibrosis (PPV-MF) or Post-essentialthrombocythemia-myelofibrosis (PET-MF) and Baseline Platelet Counts ≥50 x109/L and <100 x109/L (EXPAND)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 69
- 主要终点
- Number of Participants With Dose Limiting Toxicities
研究概览
简要总结
This is a Phase IB, open-label, dose-finding study of the JAK 1 and 2 inhibitor ruxolitinib in patients with myelofibrosis (MF). The study consists of two periods: the core study period, comprising the dose escalation stage and the safety extension phase up to Week 24, then the extension study period beyond Week 24 and up to 3 years, to further characterize the safety and efficacy of ruxolitinib in this patient population. The dose escalation phase will enroll successive cohorts of patients who receive increasing doses of ruxolitinib until the maximum safe starting dose (MSSD) is determined. In the safety expansion phase, additional patients will be treated with ruxolitinib at the MSSD defined during dose escalation. The primary objective is to establish the MSSD of ruxolitinib in patients with MF and starting platelet counts < 100 x 10 ^9/L
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 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
- •Require treatment for MF and classified at least as intermediate risk level 1 defined by the International Working Group.
- •Platelet count < 100x10 ^9/L at screening or at Study Day 1.
排除标准
- •Received platelet transfusion within 14 days prior to Screening evaluations.
研究组 & 干预措施
Stratum -1
Participants with baseline Platelet counts of 75-99 x10^9/L
干预措施: Ruxolitinib (Drug)
Stratum -2
Participants with baseline Platelet counts of 50-74 x10^9/L
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities
时间窗: 28 days
DLT was defined as the occurrence of any of the following treatment-related toxicities, occurring through Day 28: Any grade ≥ 2 hemorrhagic event ; Any grade thrombocytopenia requiring PLT transfusion; PLT count \< 25x109/L\*; Grade 4 neutropenia (absolute neutrophil count \< 0.5x109/L)\*; Grade ≥ 3 febrile neutropenia\*; Grade ≥ 2 total serum bilirubin with coincident direct bilirubin ≥ 0.5 mg/dL; Grade 3 non-hematologic toxicity for ≥ 7 consecutive days; Grade 4 non-hematologic toxicity. In the dose escalation stage in the core study period, the starting does in both strata was 5mg bid. Successive cohorts of newly enrolled patients received increasing doses of ruxolitinib until the Maximum Safe Starting Dose (MSSD) was determined. Initially, only patients with PLT counts 75-99 x10\^9/L (stratum 1) were allowed to be enrolled. Once safety was established in stratum 1 at the first 2 dose cohorts, eligible population was further expanded to patients with PLT counts 50-74 x10\^9/L (stratum 2).
次要结局
- PK- C Reactive Protein Levels by PK Quartile (AUC0-12)(24 weeks)
- AUC 0-Inf(0.25 to 0.75, 1 to 3, and 4 to 12 hours postdose on Day 1 and predose, 0.25 to 0.75 hours, and 1 to 3 hours postdose on Day 15, with a random sample on Days 29 and 57)
- PK- Interleukin 1 Receptor Antagonist Levels by PK Quartile (AUC0-12)(24 weeks)
- Number of Subjects Achieving ≥ 50% Reduction in Palpable Spleen Length(24 weeks)
- Change in Spleen Length as Measure by Palpation Over Time(Day 8, 15, 22, 29, 43, 57, 85, 113, 141, 168, 252, 336, 420, 504, 588, 672, 756, 1008, 1092)
- PK- Tissue Necrosis Factor Receptor 2 Levels by PK Quartile (AUC0-12)(24 weeks)
- Number of Treatment Emergent Adverse Events (TEAE's)(approximately 4 years)