NCT01558739已完成4 期
A UK Open-label, Multicentre, Exploratory Phase II Study of INC424 for Patients With Primary Myelofibrosis (PMF) or Post Polycythaemia Myelofibrosis (PPV MF) or Post Essential Thrombocythaemia Myelofibrosis (PET-MF)
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Treatment Success
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of INC424 in patients with PMF, PPV MF, or PET-MF using a composite measure of either an objective endpoint (> 50% reduction in splenomegaly using palpitation at 48 weeks) and/or a subjective endpoint (>50% reduction in total symptom score at 48 weeks).
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
- •Patients must not be eligible for another ongoing INC424 clinical trial.
- •Patients must be diagnosed with PMF, PPV MF or PET-MF, according to the 2008 revised World Health Organization criteria irrespective of JAK2 mutation status.
- •Patients with PMF requiring therapy must be classified as high risk (3 prognostic factors) OR intermediate risk level 2 (2 prognostic factors, no more), OR intermediate risk level 1 (1 prognostic factor, no more) with an enlarged spleen. The prognostic factors, defined by the International Working Group are:
- •Age > 65 years;
- •Presence of constitutional symptoms (weight loss, fever, night sweats); marked anemia (Hgb < 10g/dL)*;
- •Leukocytosis (history of WBC > 25 x109/L);
- •Circulating blasts > 1%. • A hemoglobin value < 10 g/dL must be demonstrated during the Screening Visit for patients who are not transfusion dependent. Patients receiving regular transfusions of packed red blood cells will be considered to have hemoglobin < 10 g/dL for the purpose of evaluation of risk factors.
- •Patients with Intermediate-1 disease and splenomegaly must have a palpable spleen measuring 5 cm or greater from the costal margin to the point of greatest splenic protrusion.
- •Patients must have a peripheral blood blast count of < 10%.
- •Patients with adequate liver function defined as direct bilirubin ≤ 2.0 x ULN and ALT ≤ 2.5 x ULN.
- •Patients with adequate renal function defined as serum creatinine ≤ 2 x ULN.
- •Patients with an ECOG performance status of 0, 1, or 2 (Appendix 5).
- •Exclusion criteria:
- •Patients eligible for hematopoietic stem cell transplantation (suitable candidate and a suitable donor is available).
- •Patients with history of malignancy in past 3 years except for treated, early-stage squamous or basal cell carcinoma in situ.
- •Patients undergoing treatment with hematopoietic growth factor receptor agonists (i.e., erythropoietin [Epo], granulocyte colony stimulating factor (GCSF [Neupogen; Neulasta], romiplostim, eltrombopag) at any time within 2 weeks prior to Screening or 4 weeks prior to Baseline.
- •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral INC424 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
- •Patients with cardiac disease which in the Investigator's opinion may jeopardize the safety of the patient or the compliance with the protocol.
- •Patients with clinically significant bacterial, fungal, parasitic or viral infection which require therapy. Patients with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.
- •Patients with known active hepatitis A, B, C or who are HIV-positive.
- •Patients with inadequate bone marrow reserve as demonstrated by:
- •Absolute neutrophil count (ANC) that is ≤ 1000/µL.
- •Platelet count that is < 100,000/µL without the assistance of growth factors, thrombopoietic factors or platelet transfusions.
- •Patients with any history of platelet counts < 50,000/µL or ANC < 500/µL except during treatment for a myeloproliferative disorder or treatment with cytotoxic therapy for any other reason.
- •Patients with coagulation parameters (PT, PTT, INR) ≥ 1.
- •Patients with known hypersensitivity to INC424 or other JAK1/2 inhibitors, or to their excipients.
- •Patients under ongoing treatment with another investigational medication or having been treated with an investigational medication within 30 days of screening.
- •Patients with any concurrent condition that, in the Investigator's opinion would jeopardize the safety of the patient or compliance with the protocol.
- •Other protocol-defined inclusion/exclusion criteria may apply.
排除标准
- 未提供
研究组 & 干预措施
INC424
Experimental
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
干预措施: INC424 (Drug)
结局指标
主要结局
Percentage of Participants With Treatment Success
时间窗: 48 Weeks
Treatment success was defined as a 50% or greater reduction in palpable spleen length versus baseline at 48 weeks and/or a 50% or greater improvement in total symptom score (derived from the MF symptom assessment form (MFSAF) questionnaire) versus baseline at the week 48 time point. The MFSAF assesses the following symptoms (all scored from absent (0) to worst imaginable (10)): general fatigue, abdominal pain (and discomfort), inactivity (ability to move and walk around), cough, night sweats, itching (pruritus), bone pain (diffuse not joint pain or arthritis), fever, change in appetite/unintentional weight loss (or gain) in past 6 months, overall quality of life (QoL).
次要结局
- Number of General Practitioner (GP), Specialists' and Urgent Care Visits(baseline to week 12, week 12 to, week 24, week 24 to week 36, week 36 to week 48)
- Change From Baseline in Myelofibrosis Symptoms Assessment Form (MF-SAF)(Baseline, week 4, week 12, week 24, week 48)
- Duration of Hospitalizations(week 48)
- Change From Baseline in EQ5D Preference Index (5 Level EuroQol Questionnaire Determining Quality of Life) From Baseline(Baseline, week 4, week 12, week 24, week 48)
- Number of Hospitalizations(week 12, week 24, week 26, week 48)
- Percentage of Participants With Transfusion Dependency Status(baseline (BL), end of treatment (up to 28 days post last treatment) (EOT))
- Percentage of Participants With Best Overall Response(week 48)
- Number of Accident & Emergency Visits From Baseline(baseline to week 12, week 12 to week 24, week 24 to week 36, week 36 to week 48)
研究者
研究点 (1)
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