An Open-Label Assessment of Safety and Efficacy of Ruxolitinib (INCB018424) in Subjects With Primary Myelofibrosis, Post- Essential Thrombocythemia Myelofibrosis, and Post-Polycythemia Vera Myelofibrosis Who Have Platelet Counts of 50 × 10^9/L to 100 × 10^9/L
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 66
- 主要终点
- Percent Change From Baseline in Total Symptom Score (TSS) as Measured by the Modified Myelofibrosis Symptom Assessment Form (MFSAF) V2.0 Diary at Week 24 by Final Titrated Dose
研究概览
简要总结
To evaluate the effects of treatment with ruxolitinib (INCB018424) on spleen volume, symptoms and potential side effects in participants with PMF, PPV-MF and PET-MF who have platelet counts of 50 x 10^9/L to 100 x 10^9/L. It is anticipated that individualized dose optimization from the starting ruxolitinib level of 5 mg bid will be associated with reductions in splenomegaly, MF-associated symptoms and inflammatory cytokine levels.
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
- •Diagnosed with PMF, PPV-MF or PET-MF as confirmed by bone marrow biopsy
- •Discontinuation of all drugs used to treat underlying MF disease at least 14 days prior to baseline visit
- •INR <= 1.5 or PTT value < 1.5 x upper limit of normal (ULN) at study entry
- •Hemoglobin level at least 6.5 g/dL at Screening visit
- •Willingness to be transfused to treat low hemoglobin levels
排除标准
- •Females who are pregnant, unable to comply with birth control use to avoid becoming pregnant or breastfeeding
- •Males who cannot comply with birth control use to avoid fathering a child
- •Platelet count < 50 x10^9/L or absolute neutrophil count (ANC) < 1 x10^9/L at the Screening visit
- •Inadequate liver or renal function; Intracranial bleeds or invasive malignancy over the previous 2 years - international normalized ratio (INR) laboratory values cannot be > 1.5 x upper limit of normal at study entry.
研究组 & 干预措施
Ruxolitinib 5 mg
Participants began administration with 5 mg ruxolitinib twice daily (BID) orally. Beginning at the Week 4 visit, doses of ruxolitinib could be increased in 5 mg once a day (QD) increments every 4 weeks every 4 weeks not to exceed a dose of 25 mg BID.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Percent Change From Baseline in Total Symptom Score (TSS) as Measured by the Modified Myelofibrosis Symptom Assessment Form (MFSAF) V2.0 Diary at Week 24 by Final Titrated Dose
时间窗: Baseline and Week 24
Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms.
Percentage of Participants With New Onset Grade 4 Thrombocytopenia Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE V4.03)
时间窗: Up to Week 156
Participants with platelet count between 50 and 100 × 10\^9/L at the screening and/or baseline visit were enrolled in the study. Thrombocytopenia is defined as a condition with low blood platelet count. Grade 4 thrombocytopenia was platelet count \< 25 × 10\^9/L. Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred.
Percentage of Participants With Treatment-emergent Adverse Events (TEAE)
时间窗: Up to Week 156
TEAE was defined as adverse events that began or worsened from baseline after the first administration of the study drug. Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred.
Percentage of Participants With New Onset Grade 2 or Higher Hemorrhage as Assessed by CTCAE V4.03
时间窗: Up to Week 156
Hemorrhages were defined as any lower level terms by MedDRA included in the Standardized MedDRA Query (SMQ) for hemorrhage terms. Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred.
Percent Change From Baseline in Spleen Volume at Week 24 by Final Titrated Dose
时间窗: Baseline and Week 24
Magnetic resonance imaging (MRI) of the upper and lower abdomen and pelvis was performed to assess spleen volumes. Computed tomography (CT) scan was performed if participant was not a candidate for MRI or if MRI was not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
次要结局
- Percent Change in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline(Baseline and Week 24)
- Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 24 Compared to Baseline(Baseline and Week 24)
- Percentage of Participants With ≥10% Reduction in Spleen Volume at Week 24 Compared to Baseline(Baseline and Week 24)
- Percentage of Participants With ≥ 50% Improvement in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline(Baseline and Week 24)
- Patient Global Impression of Change (PGIC) Score at Each Visit(Up to Week 156)
- Percent Change in Spleen Volume at Week 24 Compared to Baseline(Baseline and Week 24)
- Change in Spleen Length Measured by Palpation(Up to Week 156)
- Percent Change From Baseline in Spleen Length Measured by Palpation(Up to Week 156)