Randomized, Open Label, Multicenter Phase IIIb Study Evaluating the Efficacy and Safety of Ruxolitinib Versus Best Available Therapy in Patients With Polycythemia Vera Who Are Hydroxyurea Resistant or Intolerant (Response 2)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 149
- 试验地点
- 1
- 主要终点
- Number of Participants Achieving Hematocrit (Hct) Control at Week 28
研究概览
简要总结
This study compared the efficacy and safety of ruxolitinib to Best Available Therapy (BAT) in patients with polycythemia vera (PV) who were hydroxyurea (HU) resistant or intolerant and did not have a palpable spleen.
详细描述
This was a prospective, multi-center, open-label, randomized, Phase IIIb study evaluating efficacy and safety of ruxolitinib versus BAT as selected by the Investigator in patients with PV who are resistant to, or intolerant of HU.
The study comprised of the following periods:
Screening Period (up to 5 weeks: Day -35 to Day -1): Screening evaluations were performed at one or more clinic visits, and reviewed to determine eligibility before the patient was randomized in the study.
Core Treatment Period (Day 1 to Week 80):
Patients were randomized in 1:1 ratio to either treatment group (ruxolitinib or BAT) and were to be treated with their randomized treatment.
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
- •Confirmed diagnosis of PV according to the 2008 World Health Organization criteria, Non-palpable spleen, Phlebotomy dependent, Resistant to or intolerant of hydroxyurea, ECOG performance status of 0, 1 or 2.
排除标准
- •Inadequate liver or renal function, Significant bacterial, fungal, parasitic, or viral infection requiring treatment, Active malignancy within the past 5 years, excluding specific skin cancers, Previously received treatment with a JAK inhibitor, Being treated with any investigational agent, Women who are pregnant or nursing.
- •Other inclusion/exclusion criteria apply.
研究组 & 干预措施
Ruxolitinib
Ruxolitinib was administered at a starting dose of 10 mg twice a day (bid). Dose was adjusted based on efficacy and safety parameters up to a maximum dose of 25 mg bid.
干预措施: Ruxolitinib (Drug)
Best Available Therapy (BAT)
Best Available Therapy as selected by the investigator from: Hydroxyurea, Pegylated-Interferon (IFN/PEG-IFN), pipobroman, anagrelide, IMIDs, or observation. Participants randomized to BAT who did not respond by Week 28 were eligible to crossover and start treatment with ruxolitinib.
干预措施: Best Available Therapy (Drug)
结局指标
主要结局
Number of Participants Achieving Hematocrit (Hct) Control at Week 28
时间窗: Week 28
Proportion of patients achieving Hct control at Week 28 was defined by the absence of phlebotomy eligibility starting at Week 8 and continuing through Week 28, with no more than one phlebotomy eligibility occurring post randomization and prior to Week 8. Phlebotomy eligibility was defined by: * Confirmed Hct \> 45% that is at least 3 percentage points higher than the Hct obtained at Baseline Or * Confirmed Hct \> 48% The confirmation occurred 2 to 14 days subsequent to the initial observation.
次要结局
- Number of Participants Achieving a Complete Hematological Remission at Week 28(Week 28)
- Number of Participants Achieving a Hematocrit (Hct) Control at Week 52 and Week 80(Week 52 and 80)
- Number of Participants Achieving a Complete Hematological Remission at Week 52 and Week 80(Week 52 and 80)
- Number of Participants With Phlebotomies Over Time(Baseline to Week 260)
- Change From Baseline in Hematocrit (Hct) at Each Visit(Baseline, Week 4, 8, 12, 16, 20, 24, 28, 40, 52, 66, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234, 247 and 260)
- Change From Baseline in Hematocrit (Hct) at Each Scheduled Visit After Crossover in Participants Randomized to BAT Who Cross Over to Ruxolitinib(Baseline (last assessment before cross over), Week 4, 8, 12, 16, 20, 24, 28, 40, 52, 64, 76, 89, 102, 115, 128, 141, 154, 167, 180, 193, 206, 219 and 232 after cross-over)
- Spleen Length by Visit(Week 4, 8, 12, 16, 20, 24, 28, 40, 52, 66, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234, 247 and 260)
- Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status to Week 28(Baseline and Week 28)
- Number of Participants Achieving a Partial Remission Based on the European Leukemia Net (ELN) and International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria at Week 28(Week 28)
- Number of Participants Who Achieved Partial Remission Based on the European Leukemia Net (ELN) and International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria at Week 52 and Week 80(Week 52 and 80)
- Number of Participants Achieving a Hematocrit (Hct) Control at Week 104, Week 156, Week 208 and Week 260.(From Week 8 to Week 104, 156, 208 and 260)
- Number of Participants Achieving a Complete Hematological Remission at Week 104, Week 156, Week 208 and Week 260(From Week 8 to Week 104, 156, 208 and 260)
- Number of Participants Who Achieved Partial Remission Based on the European Leukemia Net (ELN) and International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria at Week 104, Week 156, Week 208 and Week 260.(From Week 8 to Week 104, 156, 208 and 260)
- Number of Participants With Transformation Free Survival Events(Week 260 (ruxolitinib arm) and Week 80 (BAT arm))
- Number of Participants With Overall Survival (OS) Events(up to Week 260)
- Change From Baseline in Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS)(Baseline, Week 4, 8, 16, 28, 40, 52, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247)
- Change From Baseline in Total Scores of MPN-SAF by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover(Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 40, 52, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247 after cross-over)
- Change From Baseline in Score as Per European Quality of Life 5-Dimension 5-level (EQ-5D-5L) Questionnaire(Baseline, Week 4, 8, 16, 28, 52, 80, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247)
- Change From Baseline in EQ-5D-5L VAS, by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover(Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 52, 92, 104, 117, 130, 143, 156, 169, 182, 195, 208, 221, 234 and 247 after cross-over)
- Change From Baseline in Work Productivity and Activity Impairment (WPAI) Questionnaire(Baseline, Week 4, 8, 16, 28, 52 and 80)
- Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI), by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover(Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28 and 52 after cross-over)
- Patient Global Impression of Change (PGIC)(Week 4, 8, 16, 28, 40, 52 and 80)
- Summary of Patient Global Impression of Change (PGIC), by Visit in Patients From BAT Group Who Cross Over to Ruxolitinib After Crossover(Baseline (last assessment before cross over), Week 4, 8, 16, 24, 28, 40, and 52 after cross-over)
- Number of Participants Developing Thrombosis(From randomization to Week 80 for BAT and Week 260 for Ruxolitinib)