A Phase-3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Compare Efficacy and Safety of Pomalidomide in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis and Red Blood Cell-Transfusion-Dependence
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 267
- 试验地点
- 85
- 主要终点
- Percentage of Participants Who Achieved RBC-Transfusion Independence
研究概览
简要总结
The objective of this study is to determine whether pomalidomide is safe and effective in reversing red blood cell (RBC)-transfusion-dependence in persons with myeloproliferative neoplasm (MPN)-associated myelofibrosis (global study) and in reversing anemia in Chinese with MPN-associated myelofibrosis and severe anemia not receiving RBC-transfusions (China extension study only)
详细描述
The multicenter global study was conducted in 15 countries including Australia, Austria, Belgium, Canada, China, France, Germany, Italy, Japan, the Netherlands, Russia, Spain, Sweden, the United Kingdom, and the United States. The global study enrolled participants with myeloproliferative neoplasm (MPN)-associated myelofibrosis and RBC-transfusion-dependence. Participants were randomly assigned to receive pomalidomide or placebo in a blinded fashion.
In most countries participating in the global study, RBC-transfusions are typically given for a hemoglobin level <80-90 g/L. In China, RBC-transfusions are rarely given unless the hemoglobin level is <60 g/L. Consequently, few Chinese with MPN-associated myelofibrosis meet RBC-transfusion-dependence criteria of the global study. A China-specific extension was developed to test the ability of pomalidomide to improve severe anemia (defined as a hemoglobin < 80 g/L for ≥ 84 days in persons not receiving RBC-transfusions).
The China-specific extension study consisted of a single-arm, open-label study in adults with MPN-associated myelofibrosis and severe anemia not receiving RBC transfusions with the objective of describing the frequency of anemia response.
The Global (intent-to-treat [ITT] and safety) population in the main study and the China extension (ITT and safety) population are mutually exclusive.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Age ≥ 18 years
- •Myeloproliferative-neoplasm (MPN)-associated myelofibrosis
- •RBC-transfusion-dependence (global study):
- •Average RBC-transfusion frequency ≥ 2 units/28 days over at least the 84 days immediately prior to randomization. There must be no interval > 42 days without ≥ 1 RBC-transfusion.
- •Only RBC-transfusions given when the hemoglobin ≤ 90 g/L³ are scored in
- •determining eligibility.
- •RBC-transfusions due to bleeding are not scored in determining eligibility.
- •RBC-transfusions due to chemotherapy-induced anemia are not scored in determining eligibility.
- •Severe anemia (China-specific extension):
- •≥ 2 hemoglobin concentrations ≤ 80 g/L for ≥ 84 days immediately before the day of enrollment.
- •No RBC-transfusion within 6 months prior to enrollment.
- •Hemoglobin ≤ 130 g/L at randomization (global study); ≤ 80 g/L at enrollment in the China-specific extension.
- •Bone marrow biopsy within 6 months (global study only).
- •Inappropriate to receive blood cell or bone marrow allotransplant, erythropoietin and androgenic steroids
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Agree to follow pregnancy precautions as required by the protocol.
- •Agree to receive counseling related to teratogenic and other risks of pomalidomide.
- •Agree not to donate blood or semen.
排除标准
- •Prior blood cell or bone marrow allotransplant.
- •Use of drugs to treat MPN-associated myelofibrosis ≤ 30 days before starting study drug.
- •Treatment with erythropoietin or androgenic steroids ≤ 84 days before starting study drug.
- •Anemia due to reasons other than MPN-associated myelofibrosis.
- •Pregnant or lactating females.
- •More than 10% blasts by bone marrow examination or more than 10% blasts in blood in consecutive measurements spanning at least 8 weeks
- •Prior history of malignancies,other than the disease being studied, unless the subject has been free of the malignancy for ≥ 5 years with the following exceptions:
- •Carcinoma in situ of the cervix
- •Carcinoma in situ of the breast
- •Incidental histologic finding of prostate cancer (T 1a or T 1b using TNM [tumor, nodes, metastasis] clinical staging system)
- •Human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) or hepatitis C virus (HCV) infections.
- •Prior treatment with pomalidomide.
- •Allergic reaction or rash after treatment with thalidomide or lenalidomide
- •Any of the following laboratory abnormalities:
- •Neutrophils < 0.5x10^9 /L
- •Platelets < 25 x 10^9 /L
- •Estimated glomerular filtration rate (kidney function) < 30 mL/min/1.73 m²
- •Aspartate aminotransferase (AST) and alanine transaminase (ALT) > 3.0 x upper limit of normal (ULN)
- •Total bilirubin ≥ 4 x ULN;
- •Uncontrolled hyperthyroidism or hypothyroidism.
- •Deep venous thrombosis (DVT) or pulmonary embolus (PE) < 6 months before starting study drug
- •Clinically-important heart disease within the past 6 months
研究组 & 干预措施
Pomalidomide 0.5 mg
Participants received pomalidomide 0.5 mg/day by mouth for at least 168 days unless there were unacceptable side effects or disease progression.
Participants who were RBC-transfusion independent or experienced clinical benefit (defined as a reduction from Baseline of ≥ 50% in RBC-transfusion frequency during the prior 84-day interval) could continue to receive pomalidomide until loss of RBC-transfusion independence response or clinical benefit, or other criteria for treatment discontinuation applied.
干预措施: Pomalidomide 0.5 mg (Drug)
Placebo
Participants received placebo taken by mouth once daily for at least 168 days unless there were unacceptable side effects or disease progression.
Participants who were RBC-transfusion independent or experienced clinical benefit could continue to receive placebo until loss of RBC- transfusion independence response or clinical benefit, or other criteria for treatment discontinuation applied.
干预措施: Placebo (Drug)
China Extension: Pomalidomide 0.5 mg
Participants received pomalidomide 0.5 mg/day by mouth for at least 168 days unless there were unacceptable side effects, disease progression, or they received a RBC-transfusion.
Participants who experienced anemia response could continue treatment until the response was lost or other criteria for treatment discontinuation applied.
干预措施: Pomalidomide (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved RBC-Transfusion Independence
时间窗: 168 days
RBC-transfusion independence was defined as the absence of RBC transfusions for any consecutive 84-day interval.
China Extension: Number of Participants Achieving a Hemoglobin Increase of ≥ 15 g/L Compared to Baseline for ≥ 84 Consecutive Days
时间窗: From the first dose of study drug until treatment discontinuation; median treatment duration was 24.0 weeks.
A response in the China extension study was defined as an increase in hemoglobin ≥ 15 g/L above baseline value (in the absence of RBC transfusion) for ≥ 84 consecutive days.
次要结局
- Duration of RBC-Transfusion Independence(From first dose of study drug up to 28 days after last dose, as of the data cut-off date of 16 Jan 2013; median treatment duration was 23.6 weeks in the pomalidomide arm and 23.9 weeks in the placebo arm.)
- Change From Baseline in EuroQoL-5D (EQ-5D) Visual Analog Scale(Baseline and Days 85 and 169)
- Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Total Score(Baseline and Days 85 and 169)
- Number of Participants With Treatment-emergent Adverse Events (TEAE)(From the first dose of study drug until 28 days after last dose; median treatment duration was 23.7 weeks in the pomalidomide arm, 23.9 weeks in the placebo arm, and 24.0 weeks in the China extension pomalidomide arm.)
- Healthcare Resource Utilization(From first dose of study drug up to 28 days after last dose, as of the data cut-off date of 16 Jan 2013; median treatment duration was 23.6 weeks in the pomalidomide arm and 23.9 weeks in the placebo arm.)
- Overall Survival(From first dose of study drug up to end of study; median follow-up time was 19.1 months in the pomalidomide 0.5 mg arm and 17.6 months in the placebo arm.)
- Time to RBC-Transfusion Independence(168 days)
- Change From Baseline in EuroQoL-5D (EQ-5D) Health Index Score(Baseline and Days 85 and 169)