An Open-label Assessment of an Alternative Dosing Strategy of Ruxolitinib in Patients With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, and Post-essential Thrombocythemia Myelofibrosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 45
- 主要终点
- Mean Percentage Change From Baseline in Spleen Volume at Week 24
研究概览
简要总结
The purpose of this study was to evaluate the effect of an alternative dosing strategy of ruxolitinib in subjects with primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF) and post essential thrombocythemia-myelofibrosis (PET-MF) in order to minimize the development of anemia and thrombocytopenia.
详细描述
This pilot study was designed to explore an alternative dosing approach with the purpose of reducing anemia and thrombocytopenia. Subjects began dosing at 10 mg bid and had the opportunity for dose increases based on assessments of efficacy and overall hematologic status in a defined prior dosing interval. Dose increases were restricted to those patients who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported Patient's Global Impression of Change (PGIC) score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length below the costal margin had been reduced by less than 40% at that visit relative to Baseline. Dose increases were elective and not required. Subjects were permitted a dose increase of 5 mg BID to 15 mg BID at Week 12 and to a maximum of 20 mg BID at Week 18. There were also protocol-required dose decreases for thrombocytopenia (platelets <100 x 10^9/L) or protocol-defined anemia (decline in hemoglobin of at least 2 g/dL to a level < 8 g/dL, development of transfusion dependence, or a 50% increase in transfusion requirements for transfusion dependent subjects).This approach assumed that beginning at a low dose for initial therapy might have a positive impact on the rate of the initial hemoglobin decline and the nadir by decreasing the level of JAK-mediated inhibition of hematopoiesis. Specific dose modifications were described to minimize excursions of hemoglobin levels into the Grade 3 or Grade 4 range.
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
- •Diagnosis of Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) as confirmed by bone marrow biopsy.
- •Must score at least 2 points on the Dynamic International Prognostic Scoring System (DIPSS) scale for prognostic risk factors.
- •Peripheral blast count < 5% at both Screening and Baseline hematology assessments.
- •Must discontinue all drugs used to treat underlying myelofibrosis (MF) disease no later than Day -1 (the day prior to starting ruxolitinib).
- •Must have hemoglobin value ≥ 6.5 g/dL and be willing to receive blood transfusions.
- •Platelet count ≥ 100*10^9/L.
- •Must have a palpable spleen.
排除标准
- •Inadequate liver or bone marrow reserves, end stage renal disease on dialysis, clinically significant concurrent infections requiring therapy, or unstable cardiac function.
- •Invasive malignancies over the previous 5 years (except treated early stage carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix, and completely resected papillary thyroid and follicular thyroid cancers).
- •Splenic irradiation within 6 months prior to receiving the first dose of study medication.
- •Life expectancy less than 6 months.
研究组 & 干预措施
Ruxolitinib
Participants initially received ruxolitinib 10 mg twice a day (bid) for 24 weeks. Dose increases of 5 mg bid were possible at Weeks 12 and 18 up to a maximum dose of 20 mg bid.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Mean Percentage Change From Baseline in Spleen Volume at Week 24
时间窗: Baseline to Week 24
Spleen volume was measured using magnetic resonance imaging (MRI) or computed tomography (CT) scan. The MRIs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. MRI was the preferred method for obtaining spleen volume data. CT scans were performed if the participant was not a candidate for MRI. The CT scans were processed by the same central laboratory used for MRIs. The same method (MRI or CT) was used for all visits for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred.
Median Percent Change From Baseline in Spleen Volume at Week 24
时间窗: Baseline to Week 24
Spleen volume was measured using magnetic resonance imaging (MRI) or computed tomography (CT) scan. The MRIs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. MRI was the preferred method for obtaining spleen volume data. CT scans were performed if the participant was not a candidate for MRI. The CT scans were processed by the same central laboratory used for MRIs. The same method (MRI or CT) was used for all visits for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred.
次要结局
- Percentage of Participants With a ≥ 10% Reduction From Baseline in Spleen Volume at Week 24(Baseline to Week 24)
- Percentage of Participants With a ≥ 50% Improvement From Baseline in Their Transfusion Status or With New Transfusion Independence Status for Those Participants Who Were Transfusion Dependent at Baseline(Baseline to Week 24)
- Mean Percentage Change From Baseline in the Total Symptom Score at Week 24(Baseline to Week 24)
- Percentage of Participants With a ≥ 35% Reduction From Baseline in Spleen Volume at Week 24(Baseline to Week 24)
- Median Percent Change From Baseline in Palpable Spleen Length at Week 24(Baseline to Week 24)
- Percentage of Participants With Clinically Notable Anemia(Baseline to Weeks 12, 18 and 24)
- Percentage of Participants With a ≥ 50% Improvement From Baseline in Total Symptom Score at Week 24(Baseline to Week 24)
- Number of Participants With Grade 3 or Grade 4 Adverse Events(Baseline to the end of the study)
- Median Percent Change From Baseline in the Total Symptom Score at Week 24(Baseline to Week 24)
- Mean Percentage Change From Baseline in Palpable Spleen Length at Week 24(Baseline to Week 24)
- Mean Percentage Change in Abdominal Symptom Scores at Week 24.(Week 24)
- Median Percentage Change in Abdominal Symptom Scores at Week 24.(Week 24)