A Randomized Controlled Phase 3 Study of Oral Pacritinib Versus Best Available Therapy in Patients With Thrombocytopenia and Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 311
- 试验地点
- 122
- 主要终点
- Spleen Volume Reduction
研究概览
简要总结
Phase 3, randomized, controlled study to evaluate the safety and efficacy of oral pacritinib compared to Best Available Therapy (BAT) in patients with thrombocytopenia and primary or secondary myelofibrosis.
详细描述
Multicenter, randomized, controlled, phase 3 trial comparing the safety and efficacy of pacritinib with that of BAT in patients with thrombocytopenia and primary or secondary myelofibrosis. Approximately 300 eligible patients will be randomized in a 1:1:1 allocation to pacritinib 400 mg dosed QD, pacritinib 200 mg dosed BID, or BAT (includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry). Spleen volume will be measured by MRI or CT at baseline and every 12 weeks thereafter. An independent radiology facility (IRF), blind to treatment assignments, will measure spleen volumes. Patients will also be followed for safety, Leukemia Free Survival (LFS), Overall Survival (OS), frequency of red blood cell (RBC) and platelet transfusions, and other exploratory endpoints. An Independent Data Monitoring Committee (IDMC) will evaluate the safety of pacritinib.
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
- •Intermediate -1 or -2 or high-risk Myelofibrosis (per Passamonti et al 2010)
- •Thrombocytopenia (platelet count ≤ 100,000/µL) at any time after signing informed consent
- •Palpable splenomegaly ≥ 5 cm on physical examination
- •Total Symptom Score ≥ 13 on the MPN-SAF TSS 2.0, not including the inactivity question
- •Patients who are platelet or red blood cell transfusion-dependent are eligible
- •Adequate white blood cell counts (with low blast counts), liver function, and renal function
- •At least 6 months from prior splenic irradiation
- •At least 1-4 weeks since prior myelofibrosis therapy, including any erythropoietic or thrombopoietic agent
- •Not pregnant, not lactating, and agree to use effective birth control
- •Able and willing to undergo frequent MRI or CT assessments and complete symptom assessments using a patient-reported outcome instrument
排除标准
- •Prior treatment with more than 2 JAK2 inhibitors or with pacritinib
- •There is no maximum cumulative prior JAK2 inhibitor treatment
- •History of (or plans to undergo) spleen removal surgery or allogeneic stem cell transplant
- •Ongoing gastrointestinal medical condition such as Crohn's disease, Inflammatory bowel disease, chronic diarrhea, or constipation
- •Active bleeding that requires hospitalization during the screening period
- •Cardiovascular disease, including recent history or currently clinically symptomatic and uncontrolled: congestive heart failure, arrhythmia, angina, QTc prolongation or other QTc risk factors, myocardial infarction
- •Other malignancy within last 3 years other than certain limited skin, cervical, prostate, breast, or bladder cancers
- •Other ongoing, uncontrolled illnesses (including HIV infection and active hepatitis A, B, or C), psychiatric disorder, or social situation that would prevent good care on this study
- •Life expectancy < 6 months
研究组 & 干预措施
Pacritinib, Once Daily
Pacritinib 400 mg QD
干预措施: Pacritinib (Drug)
Pacritinib, Twice Daily
Pacritinib 200 mg BID
干预措施: Pacritinib (Drug)
Best Available Therapy
BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry.
干预措施: Best Available Therapy (Drug)
结局指标
主要结局
Spleen Volume Reduction
时间窗: Baseline to Week 24
Proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline to week 24 as measured by magnetic resonance imaging (MRI) or computed tomography (CT).
Total Symptom Score (TSS) Reduction
时间窗: Baseline to Week 24
Proportion of patients achieving a ≥ 50% reduction in the total symptom score from baseline to Week 24 on the Myeloproliferative Neoplasm Symptom Assessment Form 2.0 (MPN-SAF TSS 2.0). Responses (on a scale from 0 \[absent\] to 10 \[worst imaginable\]) to questions about symptoms (tiredness, early satiety, abdominal discomfort, night sweats, pruritus, bone pain, and pain under the ribs on the left side) were used to calculate the TSS.
次要结局
未报告次要终点