2024-513605-31-00招募中2 期
A phase 2, randomized, open-label, multicenter study to evaluate safety and efficacy of single agent selinexor versus treatment of physician’s choice in patients with previously treated myelofibrosis.
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 28
- 试验地点
- 2
- 主要终点
- Rate of Spleen Volume Reduction of > or = 35% (SVR35)
研究概览
简要总结
To determine the clinical activity of selinexor monotherapy compared with physician's choice (PC) in patients with previously treated myelofibrosis (MF).
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 years 至 64 years（18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •A diagnosis of primary MF or post-ET or post-PV MF according to the 2016 WHO classification of MPN, confirmed by the most recent local pathology report.
- •Calculated creatinine clearance (CrCl) >15 mL/min based on the Cockcroft and Gault formula.
- •Patients with active hepatitis B virus (HBV) are eligible if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 IU/mL.
- •Patients with untreated hepatitis C virus (HCV) are eligible if there is a documentation of negative viral load per institutional standard.
- •Patients with history of human immunodeficiency virus (HIV) are eligible if they have CD4+ T-cell counts > or = 350 cells/microL, negative viral load per institutional standard, and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year.
- •Female patients of childbearing potential must have a negative serum pregnancy test at screening and agree to use highly effective methods of contraception throughout the study and for at least 90 days after the last dose of selinexor, or for the duration as stated on the label (SmPC/USPI) for those on the comparator drug (physician's choice arm). Childbearing potential excludes: Age >50 years and naturally amenorrhoeic for >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy.
- •Male patients who are sexually active must use highly effective methods of contraception throughout the study and for at least 90 days after the last dose of selinexor, or for the duration as stated on the label (SmPC/USPI) for those on the comparator drug (physician's choice arm). Male patients must agree not to donate sperm during the study treatment period.
- •Patients must sign written informed consent in accordance with federal, local and institutional guidelines.
- •Previous treatment with JAK inhibitors for at least 6 months.
- •Measurable splenomegaly during the screening period as demonstrated by spleen volume of > or = 450 cm3 by MRI or CT scan
- •Relapsed, refractory or intolerant to JAK inhibitors as defined as meeting one of the criteria below: <35% spleen volume reduction by MRI or CT-scan (from baseline) or b. <50% decrease in spleen size by palpation (from baseline) or an increase of at least 3 cm with the spleen at least 5 cm below the left costal margin or c. Spleen volume increase >25% from nadir or a return to within 10% of baseline) after any initial response or d. Treatment with JAK inhibitor was complicated by development of RBC transfusion requirement (2 units per month for 2 month); or grade 3 thrombocytopenia, anemia, hematoma/hemorrhage; or Grade 2 non-hematologic toxicity while on JAK inhibitors
- •Patients > or = 18 years of age
- •ECOG < or = 2
- •Platelet count > or = 75 × 10^9/L
- •Absolute neutrophil count (ANC) > or = 1.5 × 10^9/L
- •Serum direct bilirubin < or =1.5 × ULN; AST and ALT < or = 2.5 × ULN
排除标准
- •>5% blasts in peripheral blood or >10% blasts in bone marrow (i.e., accelerated phase).
- •Patients with contraindications to use of selinexor or all the drugs intended to be used in the comparative treatment arm.
- •Previous treatment with selinexor or other XPO1 inhibitors.
- •Use of any standard or experimental anti-MF therapy <21 days prior to Cycle 1 Day 1 (hydroxyurea or growth factors are allowed).
- •Impairment of gastrointestinal (GI) function or GI disease that could significantly alter the absorption of selinexor (Example: vomiting, or diarrhea that is CTCAE grade >1).
- •Received strong cytochrome P450 3A (CYP3A) inhibitors < or = 7 days prior to selinexor dosing OR strong CYP3A inducers < or = 14 days prior to selinexor dosing.
- •Major surgery <28 days prior to C1D
- •Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral).
- •Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient's safety, prevent the patient from giving informed consent, or being compliant with the study procedures.
- •Female patients who are pregnant or lactating.
结局指标
主要结局
Rate of Spleen Volume Reduction of > or = 35% (SVR35)
Rate of Spleen Volume Reduction of > or = 35% (SVR35)
次要结局
- Rate of Spleen Volume Reduction of > or =25% (SVR25)
- Overall survival (OS)
- Rate of Total Symptom Score reduction of > or = 50% (TSS50) in the myelofibrosis symptom assessment form (MFSAF) V4.0, based on local assessment
- Anemia response as defined per the IWG-MRT criteria, based on local assessment • Duration of SVR35 and SVR25 • Duration of TSS50 based on local assessment • ORR (Complete Response [CR] + Partial Response [PR] + Clinical Improvement [CI]) by IWG-MRT criteria, based on local assessment
- The occurrence, nature, and severity of AEs
- Population PK derived parameters: • AUC • Cmax
研究者
clinical Trial Information Desk
Scientific
Karyopharm Therapeutics Inc.
研究点 (2)
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