A Phase 2 Study to Evaluate the Efficacy and Safety of Selinexor Monotherapy in Subjects With JAK Inhibitor-naïve Myelofibrosis and Moderate Thrombocytopenia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 58
- 试验地点
- 70
- 主要终点
- Proportion of Participants with Spleen Volume Reduction ≥35% (SVR35) at Week 24
研究概览
简要总结
The main purpose of this study is to evaluate the efficacy of selinexor in JAKi-naïve participants with myelofibrosis (MF) and with normal platelet counts or with mild to moderate thrombocytopenia based on spleen volume reduction (SVR). Additional efficacy and safety parameters will also be assessed during the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •A diagnosis of MF or post-ET or post-PV MF according to the 2016 World Health Organization (WHO) classification of MPN, confirmed by the most recent local pathology report
- •Measurable splenomegaly during the screening period as demonstrated by spleen volume of greater than or equal to (>=) 450 cubic square centimeter (cm^3) by MRI or CT scan (results from MRI or CT imaging performed within 28 days prior to C1D1 are acceptable)
- •DIPSS risk category of intermediate-1 with symptoms, or intermediate-2, or high-risk
- •ECOG Performance Status less than or equal to (<=) 2
- •Platelet count of greater than or equal to (>=) 50 x 10^9/L without platelet transfusion within 7 days prior to the first dose of selinexor
- •Absolute neutrophil count (ANC) >=1.0 × 10^9/L without need for growth factors within 7 days prior to the first dose of selinexor
- •Adequate liver function as defined by the following: aspartate transaminase (AST) and alanine transaminase (ALT) <= 2.5 × upper limit normal (ULN) and serum total bilirubin <= 3×ULN
- •Calculated creatinine clearance (CrCl) greater than (>) 15 milliliter per minute (mL/min) based on the Cockcroft and Gault formula
- •Active symptoms of MF as determined by presence of at least 2 symptoms with an average score >= 5 or total score of >= 12 at screening (at least 5 of 7 consecutive days immediately preceding C1D1) using the MFSAF V4.0
- •Must provide bone marrow biopsy samples (samples obtained up to 3 months prior to C1D1 are permitted) at screening and during the study
- •Currently not eligible for stem cell transplantation
- •Must be willing to complete the MFSAF V4.0 daily during the study for evaluating the symptom response (i.e., TSS50)
排除标准
- •More than 10% blasts in peripheral blood or bone marrow (accelerated or blast phase)
- •Previous treatment with JAK inhibitors for MF
- •Previous treatment with selinexor or other XPO1 inhibitors
- •Females who are pregnant or lactating
- •Prior splenectomy, splenic radiation, or a splenic embolization within 6 months prior to C1D1
- •History of myocardial infarction, unstable angina, percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft (CABG), cerebrovascular accident (transient ischemic attack [TIA]), ventricular arrhythmias, congestive heart failure class > 2 per New York Heart Association (NYHA) within 6 months of C1D1
- •Unable to tolerate two forms of antiemetics prior to each dose for the first two cycles
研究组 & 干预措施
Selinexor 60 mg (Arm 1)
Participants will receive selinexor 60 milligrams (mg) oral tablets once weekly (QW) (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment. Optional add-on medication dosing may be initiated based on Spleen Volume Reduction (SVR) values at Week 12 or Week 24 of treatment.
干预措施: Selinexor 60 mg (Drug)
Selinexor 60 mg (Arm 1)
Participants will receive selinexor 60 milligrams (mg) oral tablets once weekly (QW) (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment. Optional add-on medication dosing may be initiated based on Spleen Volume Reduction (SVR) values at Week 12 or Week 24 of treatment.
干预措施: Ruxolitinib (Drug)
Selinexor 60 mg (Arm 1)
Participants will receive selinexor 60 milligrams (mg) oral tablets once weekly (QW) (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment. Optional add-on medication dosing may be initiated based on Spleen Volume Reduction (SVR) values at Week 12 or Week 24 of treatment.
干预措施: Pacritinib (Drug)
Selinexor 60 mg (Arm 1)
Participants will receive selinexor 60 milligrams (mg) oral tablets once weekly (QW) (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment. Optional add-on medication dosing may be initiated based on Spleen Volume Reduction (SVR) values at Week 12 or Week 24 of treatment.
干预措施: Momelotinib (Drug)
Selinexor 40 mg (Arm 2)
Participants will receive selinexor 40 mg oral tablets QW (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment. Optional add-on medication dosing may be initiated based on Spleen Volume Reduction (SVR) values at Week 12 or Week 24 of treatment.
干预措施: Selinexor 40 mg (Drug)
Selinexor 40 mg (Arm 2)
Participants will receive selinexor 40 mg oral tablets QW (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment. Optional add-on medication dosing may be initiated based on Spleen Volume Reduction (SVR) values at Week 12 or Week 24 of treatment.
干预措施: Ruxolitinib (Drug)
Selinexor 40 mg (Arm 2)
Participants will receive selinexor 40 mg oral tablets QW (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment. Optional add-on medication dosing may be initiated based on Spleen Volume Reduction (SVR) values at Week 12 or Week 24 of treatment.
干预措施: Pacritinib (Drug)
Selinexor 40 mg (Arm 2)
Participants will receive selinexor 40 mg oral tablets QW (Days 1, 8, 15, and 22 of each 28-day cycle) until PD, intolerable toxicity, or until they meet the criteria for discontinuation of study treatment. Optional add-on medication dosing may be initiated based on Spleen Volume Reduction (SVR) values at Week 12 or Week 24 of treatment.
干预措施: Momelotinib (Drug)
结局指标
主要结局
Proportion of Participants with Spleen Volume Reduction ≥35% (SVR35) at Week 24
时间窗: At Week 24
Measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) Scan by Investigator assessment.
次要结局
- Absolute Mean Change in Total Symptom Score (Abs-TSS) from baseline to Week 24(At Baseline and Week 24)
- Incidence and severity of TEAEs, including TRAEs and SAEs(From Baseline to EoS (approximately 48 months))