A Phase 1/2, Open-Label Study of the JAK2 Inhibitor INCB018424 Administered Orally to Patients With Primary Myelofibrosis (PMF) and Post Polycythemia Vera/Essential Thrombocythemia Myelofibrosis (Post-PV/ET)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 154
- 主要终点
- Percentage of Participants With Clinical Improvement (CI) Over Time
研究概览
简要总结
To determine the safety, tolerability and effectiveness of ruxolitinib (INCB018424), administered orally to patients with Primary Myelofibrosis (PMF), Post Polycythemia Vera Myelofibrosis (PPV-MF) and Essential Thrombocythemia Myelofibrosis (PET-MF).
详细描述
This is a multicenter, open-label, non-randomized, dose escalation study of ruxolitinib, a small molecule Janus kinase (JAK) inhibitor, administered orally to patients with PMF, PPEV-MF or PET-MF. The study is comprised of 3 parts:
Part 1: Dose escalation and determination of maximum tolerated dose (complete).
Part 2: Exploration of alternative dosing schedules (complete).
Part 3: Further evaluation of selected dose regimens, including additional response measures to explore effect of ruxolitinib on symptoms and other parameters including daily physical activity and long-term survival (ongoing).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Diagnosed with PMF or Post-PV/ET MF
- •Patients with myelofibrosis requiring therapy
- •Adequate bone marrow reserve
排除标准
- •Received anti-cancer medications or investigational therapy in the past 14 days
研究组 & 干预措施
Ruxolitinib
All participants received oral ruxolitinib. Patients began treatment with either 10 mg twice a day (bid), 15 mg bid, 25 mg bid, 50 mg bid, 25 mg once a day (qd), 50 mg qd, 100 mg qd, or 200 mg qd, depending on the time period when they entered the study. The doses were titrated based on efficacy and safety to a maximum of 25 mg bid for patients who entered the study after sufficient dosing information had been obtained to define the maximum dose for patients in the study. Patients could continue receiving treatment indefinitely if receiving benefit at a dose that continues to maintain benefit but does not exceed a maximum dose of 25 mg BID.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Percentage of Participants With Clinical Improvement (CI) Over Time
时间窗: Week 12, 24, 36, 48 and 60
Clinical improvement was defined according to the International Working Group Myelofibrosis Research and Treatment criteria, and required 1 of the following: 1. A ≥ 2 g/dL increase in Hemoglobin level or becoming transfusion independent; 2. Either a ≥ 50% reduction in palpable splenomegaly if spleen was ≥ 10 cm at Baseline or a spleen palpable at \> 5 cm at Baseline becomes not palpable; 3. A ≥ 100% increase in platelet count and an absolute platelet count of ≥ 50,000 x 10\^9/L or 4. A ≥ 100% increase in absolute neutrophil count (ANC) and an ANC of ≥ 0.5 x 10\^9/L.
Number of Participants With Adverse Events (AEs)
时间窗: From Baseline to the interim clinical cut-off date (31 December 2009). The median time on study was 14.8 months, with a range of 26 days to 29.7 months. As of March 1, 2011 the total exposure to ruxolitinib was 269 patient-years.
Treatment-Emergent AEs are events occurring after first drug administration or worsened from baseline. Treatment-Related AEs are those with a definite, probable, possible or missing causality. A serious AE is a medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is a medical event requiring intervention to prevent 1 of the above. A severe or life-threatening AE is based on intensity, according to National Cancer Institute-Common Toxicity Criteria for Adverse Effects (NCI-CTCAE) v3.0.
次要结局
- Percentage of Participants With ≥ 35% Reduction From Baseline in Spleen Volume Over Time(Baseline, Weeks 4, 12, 24 and 48)
- Change From Baseline in Myelofibrosis Total Symptom Score at Week 24(Baseline and Week 24)
- Change From Baseline to Week 24 in Health-Related Quality of Life(Baseline and Week 24)
- Change From Baseline in Body Weight Over Time(Baseline and Weeks 4, 8, 12, 24, 36, 48 and 60.)
- Percentage of Participants Achieving ≥ 50% Reduction From Baseline in Spleen Palpation Length Over Time(Baseline and Weeks 4, 8, 12, 24, 36, 48 and 60)
- Change From Baseline to Week 24 in Eastern Cooperative Oncology Group (ECOG) Performance Status(Baseline and Week 24)