CTRI/2012/08/002911Other2 期
A Three-part Study of Eltrombopag in ThrombocytopenicSubjects with Myelodysplastic Syndromes or Acute MyeloidLeukemia (Part 1: open-label, Part 2: randomized, double-blind,Part 3: extension).ASPIRE: A Study of EltromboPag In MyelodysplasticSyndRomes and AcutE Myeloid Leukemia
适应症
试验速览
- 阶段
- 2 期
- 状态
- Other
- 入组人数
- 140
- 试验地点
- 9
- 主要终点
- The primary objective of this study is to determine the reduction in the number of clinically relevant thrombocytopenic events (CRTE) in subjects with MDS or AML who have Grade 4 thrombocytopenia and are treated with eltrombopag compared to those treated with placebo.
研究概览
简要总结
Thrombocytopenia is a significant problem for patients with malignancies and can be life-threatening. The etiology of thrombocytopenia depends on the specific type and location of the malignancy, and may encompass an autoimmune component, the presence of splenomegaly and/or prior and current treatments.
In myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), megakaryopoiesis can be impaired in both a quantitative (lack of megakaryocytes), and qualitative way (increased apoptosis in megakaryocytes from patients with MDS). Interestingly, increased apoptosis of megakaryocytes has also been observed in idiopathic thrombocytopenic purpura (ITP) [Houwerzijl, 2005]. Based on the pathophysiology of thrombocytopenia in MDS and AML and based on eltrombopag’s known mechanism of action, it is very likely that eltrombopag will be able to increase platelet counts and reduce thrombocytopenic sequelae (platelet transfusions and haemorrhages) in patients with MDS and AML.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 55.00 Year(s)（—）
- 性别
- All
入选标准
- •Adult subjects (18 years of age or older) with MDS or AML (bone marrow blasts ≤50%) with thrombocytopenia due to bone marrow insufficiency from the disease or prior treatment.
- •Subjects with transient thrombocytopenia due to active treatment with disease modifying agents or chemotherapy (except for hydroxyurea) are excluded.
- •Subjects must have Grade 4 thrombocytopenia (platelet counts <25 Gi/L) due to bone marrow insufficiency (or platelet count ≥25 Gi/L due to platelet transfusion).
- •Subjects must have platelet count, bleeding and platelet transfusion data available over a period of at least 4 weeks prior to randomization.
- •Prior systemic treatment for malignancy, with the exception of hydroxyurea (see Section 6.1.2), must have been discontinued prior to entry into the study: • at least 4 weeks before Day 1 for the following: chemotherapy, demethylating agents (azacitidine or decitabine), lenalidomide, thalidomide, clofarabine and IL- 11(oprelvekin); • at least 8 weeks before Day 1 for antithymocyte/antilymphocyte globulin.
- •Subjects with a prior stem cell transplant (SCT) must have relapsed after the SCT.
- •Subjects must have stable disease (as defined by treatment guidelines and investigator discretion) and, in the opinion of the investigator, must be expected to complete a 12 week treatment period.
- •ECOG Status 0-
- •Subject must be able to understand and comply with protocol requirements and instructions.
- •Subject has signed and dated an informed consent form.
- •Adequate baseline organ function defined by the criteria below: • total bilirubin ≤ 1.5xULN except for Gilbert’s syndrome or cases clearly not indicative of inadequate liver function (i.e. elevation of indirect (hemolytic) bilirubin in the absence of ALT abnormality) • ALT ≤ 3xULN • creatinine ≤ 2.5xULN
- •Women must be either of non-child bearing potential (see Section 7.3.12.2.1, for definition) or women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study (See Section 7.3.12.2, for acceptable methods of birth control).
- •Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose of study treatment.
- •In France, a subject will be eligible for inclusion in this study only if either affiliated to, or a beneficiary of, a social security category.
排除标准
- •Subjects with MDS and an IPSS of low or intermediate-1 risk.
- •Subjects with a diagnosis of acute promyelocytic or megakaryocytic leukemia or AML secondary to a myeloproliferative neoplasm.
- •History of treatment with romiplostim or other TPO-R agonists.
- •Subjects with a QTc 480 msec (QTc 510 msec for subjects with Bundle Branch Block) at baseline.
- •Subjects with a palpable spleen must have a splenic ultrasound to confirm spleen length is ≤16 cm.
- •Subjects with palpable spleen 16 cm are not eligible.
- •Leukocytosis ≥25,000/uL on Day 1 of treatment with study medication.
- •Subjects with known thrombophilic risk factors.
- •Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator.
- •Female subjects who are nursing or pregnant (positive serum or urine β-human chorionic gonadotropin [β-hCG] pregnancy test) at screening or pre-dose on Day
- •Current alcohol or drug abuse.
- •Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
- •Active and uncontrolled infections (e.g. sepsis).
- •Subjects infected with Hepatitis B, C or Human Immunodeficiency Virus (HIV).
- •Subjects with liver cirrhosis (as determined by the investigator).
- •Subjects receiving or planned to receive any prohibited medication (see Section 6.2).
- •Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or excipient (microcrystalline cellulose, mannitol, polyvinylpyrrolidine, sodium starch glycolate, magnesium stearate,hypromellose, titanium dioxide, polyethylene glycol 400 and polysorbate 80) that contraindicates the subjects’ participation.
- •In France, subjects who have participated in any study using an investigational drug during the previous 30 days.
结局指标
主要结局
The primary objective of this study is to determine the reduction in the number of clinically relevant thrombocytopenic events (CRTE) in subjects with MDS or AML who have Grade 4 thrombocytopenia and are treated with eltrombopag compared to those treated with placebo.
时间窗: The primary endpoint is clinically relevant thrombocytopenic events (CRTE) during weeks 5-12 of treatment.
次要结局
- To evaluate the effect of eltrombopag on the need for platelet transfusions.(To evaluate hematologic improvement)
- To evaluate the effect of eltrombopag on the duration of platelet transfusion independence.(To evaluate the effect of eltrombopag on bleeding symptoms.)
- To evaluate overall survival(To evaluate the safety and tolerability of eltrombopag.)
- Secondary objectives compare the following in subjects treated with eltrombopag and placebo:(Secondary endpoints compare the following in subjects treated with eltrombopag and placebo:)
研究者
研究点 (9)
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