NCT03627403终止2 期
A Phase II Study to Evaluate the Efficacy and Safety of Selinexor in Patients With Myelofibrosis Refractory or Intolerant to JAK1/2 Inhibitors
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 2
- 主要终点
- Count of Participants With Reduction in Spleen Volume
研究概览
简要总结
This is a phase II, open label, prospective, single-arm study evaluating the efficacy and safety of selinexor in patients with PMF or secondary MF (PPV-MF or PET-MF) who are refractory or intolerant to ruxolitinib and/or any other experimental JAK1/2 inhibitors.
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
- •Male or female subject aged ≥ 18 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Diagnosis of primary myelofibrosis (PMF), post-essential thrombocytosis (PET-MF) or post-polycythemia vera (PPV-MF).
- •Life expectancy ≥ 6 months.
- •Prior treatment with ruxolitinib or any experimental JAK1/2 inhibitor with any one or more of the following:
- •a. Inadequate response after being on ≥ 3 months of treatment defined by: i. Palpable spleen ≥ 10 cm below the left subcostal margin on physical examination at the screening visit OR ii. Palpable spleen ≥ 5cm below the left subcostal margin on physical examination at the screening visit AND active symptoms of MF at the screening visit defined presence of 1 symptom score of ≥ 5 or two symptom scores each of ≥ 3 using the Screening Symptoms Form (Appendix 6) b. Intolerant to ruxolitinib and/or other JAK1/2 inhibitors due to any grade ≥ 3 non-hematologic AEs of or any grade ≥ 2 AEs requiring treatment discontinuation AND palpable spleen ≥ 5cm below the left subcostal margin on physical examination at the screening visit.
- •Adequate organ function as defined as:
- •Hematologic (≤ 28 days prior to C1D1):
- •Total white blood cell (WBC) count ≥ 1000/mm3
- •Absolute neutrophil count (ANC) ≥ 500/mm3
- •Hemoglobin ≥ 7 g/dL
- •Platelet count ≥ 30,000/mm3
- •For patients receiving transfusion and growth factor support, the following delays must be observed between the last administration and hematologic laboratory screening assessments:
- •For hematopoietic growth factor support (including erythropoietin, darbepoetin, granulocyte-colony stimulating factor [G-CSF], granulocyte macrophage-colony stimulating factor [GM-CSF], and platelet stimulators [e.g., eltrombopag, romiplostim, or interleukin-11]): at least 2 weeks.
- •Growth factor support, RBC and/or platelet transfusions are allowed as clinically indicated per institutional guidelines during the study.
- •Hepatic (≤ 28 days prior to C1D1):
- •Total bilirubin < 1.5 × ULN except in patients with indirect hyperbilirubinemia due to hemolysis or with Gilbert's syndrome where total bilirubin should be < 5 × ULN
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 × ULN.
- •Renal (within 28 days prior to C1D1):
- •Estimated creatinine clearance (CrCl) ≥ 20 mL/min using the Cockcroft and Gault formula [(140-Age) × Mass (kg)/(72 × creatinine mg/dL), multiply by 0.85 if the patient is female] OR
- •Female patients of childbearing potential must have a negative serum pregnancy test (≤ 3 days prior to C1D1).
- •Female patients of childbearing potential must agree to use 2 methods of contraception throughout the study and for 3 months following the last dose of study treatment (including 1 highly effective and 1 effective method of contraception as defined in section 7.4)
- •Male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential.
- •Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior treatments including ruxolitinib or other experimental agents unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
- •Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
排除标准
- •Prior exposure to a SINE compound, including selinexor.
- •Patients who are below their ideal body weight and would be unduly impacted by changes in their weight, in the opinion of the investigator, will be excluded
- •Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals ≤ 1 week prior to C1D
- •Patients on prophylactic antibiotics or with a controlled infection ≤ 1 week prior to C1D1 are acceptable.
- •Radiation, chemotherapy, immunotherapy, or any other anticancer therapy (including investigational therapies) ≤ 2 weeks.
- •Ruxolitinib or other JAK1/2 inhibitors ≤ at least 3 days or 5 half-lives prior to C1D
- •Major surgery ≤ 4 weeks prior to C1D
- •Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus ribonucleic acid (RNA) or hepatitis B virus surface antigen.
- •Any active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment.
- •Any life-threatening illness, organ system dysfunction, or serious psychiatric, medical, or other conditions/situations which, in the investigator's opinion, could compromise a patient's ability to give informed consent, safety, or compliance with the protocol.
- •Contraindication to any of the required concomitant drugs or supportive treatments.
- •Subjects taking prohibited medications as described in Section 6.
- •Following discontinuation of prohibited medications, a washout period is required prior to initiating study treatment (the duration of the washout must be as clinically indicated, e.g. at least five half-lives).
- •Subjects who are breastfeeding and unwilling to stop while on study
研究组 & 干预措施
Selinexor, all patients
Experimental
Single Arm Study, all patients will get selinexor
干预措施: Selinexor (Drug)
结局指标
主要结局
Count of Participants With Reduction in Spleen Volume
时间窗: Up to 5.5 months
To assess the efficacy of selinexor on spleen volume reduction in subjects with myelofibrosis (PMF, PET-MF, or PPV-MF) refractory or intolerant to ruxolitinib and/or any other experimental JAK1/2 inhibitors. This outcome will report the number of subjects with ≥ 35% reduction in spleen volume as measured by MRI or CT abdomen from baseline to after six cycles of treatment or end of treatment. Patients who did not complete six cycles of treatment received an MRI at discontinuation of therapy. Patients who died prior to completing six cycles of treatment or a follow-up scan were considered non-responders.
次要结局
- Adverse Events That Occur(Up to 24 months)
- Percent Change of Spleen Volume(Up to 5.5 months)
- Change in Symptoms Score(Up to 5.5 months)
- Overall Response(Up to 24 months)
- Overall Survival(Up to 24 months)
研究者
研究点 (2)
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