An Open Label, Sequential Cohort, Dose Escalation Study to Evaluate the Safety and Efficacy of AMG 531 in Thrombocytopenic Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 72
- 主要终点
- Part A: Number of Participants With Adverse Events
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of romiplostim in thrombocytopenic patients with low or Intermediate-1 risk MDS. In addition, the study will evaluate the platelet response to romiplostim.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 MDS using the World Health Organization classification
- •Low or Intermediate-1 risk MDS using the International Prognostic Scoring System (IPSS)
- •The mean of two platelet counts taken during the screening period must be ≤ 50 x 10^9/L, with no individual count > 55 x 10^9/L (The mean platelet counts of 5 subjects enrolled at the maximum tolerated dose (MTD) must be ≤ 20 x 10^9/L). Standard of care platelet assessments taken prior to Informed Consent may be used as 1 of the 2 counts taken within 3 weeks prior to study day
- •Must be ≥ 18 years of age at the time of obtaining informed consent
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at the time of screening
- •Adequate Liver Function, as evidenced by a serum bilirubin ≤ 1.5 times the laboratory normal range (except for patients with a confirmed diagnosis of Gilbert's Disease), alanine aminotransferase (ALT) ≤ 3 times the laboratory normal range, and aspartate aminotransferase (AST) ≤ 3 times the laboratory normal range
- •A serum creatinine concentration ≤ 2 mg/dL (≤ 176.6 µmol/L)
- •Before any study-specific procedure, the appropriate written informed consent must be obtained (see Section 12.1)
排除标准
- •Currently receiving any treatment for MDS other than transfusions and erythropoietic growth factors. If granulocyte growth factors are currently being received, they cannot be used on or after study day 1
- •Clinically significant bleeding within 2 weeks prior to screening (eg, gastrointestinal (GI) bleeds, intracranial hemorrhage)
- •Prior malignancy (other than controlled prostate cancer, in situ cervical cancer or basal cell cancer of the skin) unless treated with curative intent and without evidence of disease for ≥ 3 years before screening
- •Prior history of bone marrow transplantation
- •Persistent peripheral blood monocytosis (≥ 3 months with an absolute monocyte count > 1,000/µL)
- •Unstable angina, congestive heart failure (New York Heart Association [NYHA] > class II), uncontrolled hypertension (diastolic > 100 mmHg), uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction
- •Received Anti-Thymocyte Globuline (ATG) within 6 months of screening
- •Received hypomethylating agents, immunomodulating agents, histone deacetylase inhibitors, cyclosporine or mycophenolate within 6 weeks of screening
- •Received interleukin (IL)-11 (oprelvekin) within 4 weeks before screening
- •Concurrent use of granulocyte growth factors (i.e. granulocyte-colony stimulating factor [G-CSF; Neupogen, Granocyte], pegfilgrastim [Neulasta], granulocyte macrophage-colony stimulating factor [GM-CSF; Leukine, Prokine, Sargramostim])
- •Have ever previously received recombinant thrombopoietin (rTPO), pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), eltrombopag, or romiplostim
- •Less than 4 weeks since receipt of any therapeutic drug or device that is not Food and Drug Administration (FDA) approved for any indication
- •Other investigational procedures are excluded
- •History of arterial thrombosis (eg, stroke or transient ischemic attack) in the past year
- •History of venous thrombosis that currently requires anti-coagulation therapy
- •Untreated B12 or folate deficiency
- •Subject is evidently pregnant (eg, positive human chorionic gonadotropin [HCG] test) or is breast feeding
- •Subject is not using adequate contraceptive precautions
- •Subject has known hypersensitivity to any recombinant E coli-derived product
- •Subject previously has enrolled in this study
- •Subject will not be available for follow-up assessment
- •Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
研究组 & 干预措施
Part A: 300 µg romiplostim
Cohort 1 in Part A, participants received romiplostim 300 µg subcutaneously once weekly for 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.
干预措施: Romiplostim (Drug)
Part A: 700 µg romiplostim
Cohort 2 in Part A, participants received romiplostim 700 µg subcutaneously once weekly for up to 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.
干预措施: Romiplostim (Drug)
Part A: 1000 µg romiplostim
Cohort 3 in Part A, participants received romiplostim 1000 µg subcutaneously once weekly for up to 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.
干预措施: Romiplostim (Drug)
Part A: 1500 µg romiplostim
Cohort 4 in Part A, participants received romiplostim 1500 µg subcutaneously once weekly for up to 3 weeks. Participants who completed Part A could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.
干预措施: Romiplostim (Drug)
Part B: 750 µg romiplostim SC QW
Part B participants received romiplostim 750 µg subcutaneously (SC) once weekly (QW) for 8 weeks. Participants who complete Part B could continue to receive weekly injections of romiplostim for up to 1 year in the extension treatment phase.
干预措施: Romiplostim (Drug)
Part B: 750 µg romiplostim SC Q2W
Part B participants received romiplostim 750 µg subcutaneously every two weeks (Q2W) for 8 weeks. Participants who complete Part B could continue to receive injections of romiplostim for up to 1 year in the extension treatment phase.
干预措施: Romiplostim (Drug)
Part B: 750 µg romiplostim IV Q2W
Part B participants received romiplostim 750 µg intravenously (IV) once every two weeks for 8 weeks. Participants who complete Part B could continue to receive romiplostim for up to 1 year in the extension treatment phase.
干预措施: Romiplostim (Drug)
结局指标
主要结局
Part A: Number of Participants With Adverse Events
时间窗: Treatment period (4 weeks) plus treatment extension (1 year)
The number of participants experiencing one or more adverse events during the treatment phase or extension phase of Part A.
Part B: Number of Participants With Adverse Events
时间窗: Treatment period (8 weeks) plus treatment extension (1 year)
The number of participants experiencing one or more adverse events during the treatment phase or extension phase of Part B.
次要结局
- Part A: Number of Participants With a Complete or Major Platelet Response(Treatment Period (4 weeks))
- Part B: Number of Participants With a Complete or Major Platelet Response(Treatment Period (8 weeks))
- Part A: Number of Participants With a Platelet Response Per IWG Criteria(Treatment period (4 weeks) and extension period (52 weeks).)
- Part B: Peak Platelet Count(Treatment Period (8 weeks))
- Part B: Week 1 Cmax(Week 1)
- Part B: Number of Participants With a Platelet Response Per IWG(Treatment period (8 weeks) and extension period (52 weeks).)
- Part B: Duration of Platelet Response(Treatment Period (8 weeks) and extension period (52 weeks))
- Part B: Week 1 Ctrough(Week 1)
- Part B: Week 1 AUC0-4(Week 1)
- Part B: Week 7 Ctrough(Week 7)
- Part B: Time to First Platelet Response(Treatment Period (8 weeks) and extension period (52 weeks).)
- Part B: Week 7 AUC0-4(Week 7)
- Part B: Week 1 Tmax(Week 1)
- Part B: Week 7 Tmax(Week 7)
- Part B: Week 7 Cmax(Week 7)