Long Term Outcomes of Eltrombopag in Patients With Bone Marrow Aplasia, Assiut University Hospital Insight.
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 3
- 主要终点
- Determine overall survival rate.
研究概览
简要总结
Bone marrow aplasia, also known as aplastic anemia (AA) is a potentially fatal bone marrow failure syndrome characterized by a paucity of hematopoietic stem cells (HSCs) and progenitor cells with varying degrees of cytopenia and fatty infiltration of the bone marrow space. Underlying mechanisms include immune-mediated attack, telomere defects, and inherent HSC compartment insufficiency. These events may occur individually or in concert, mostly involving effector T cells Historical treatment has included the use of high-dose chemotherapy and allogeneic stem cell transplantation as well as lymphotoxic immunosuppressive therapy (IST) Thrombopoietin (TPO) regulates platelet production, maturation, and release through binding of c-mpl on megakaryocytes.
详细描述
Eltrombopag (E-PAG) is an oral synthetic small-molecule, noncompetitive, TPO agonist that initially was approved by the US Food and Drug Administration (FDA) for the treatment of chronic immune thrombocytopenic purpura. Single-agent activity of E-PAG was demonstrated in at least 1 lineage in 40 to 45% of patients with AA that was refractory to IST, leading to its approval by the FDA in this setting (5).
Eltrombopag evades cytokines blockade of c-MPL signaling and activates the c-MPL receptor by interacting with the transmembrane receptor domain, resulting in a conformational change without competing with TPO. Regarding AA, it is possible that eltrombopag promotes DNA repair in hematopoietic stem cells and progenitor cells. However, AA may appear to evolve to other hematologic diseases, most notably paroxysmal nocturnal hemoglobinuria and myelodysplastic syndrome, even to acute myeloid leukemia, and about 15% of patients evolve to myelodysplastic syndrome, acute myeloid leukemia or both after immunosuppressive therapy. Therefore, it is unclear but alarming that the use of eltrombopag exacerbates the clone evolution (6).
Eltrombopag and cyclosporin was active as front-line treatment of severe aplastic anaemia, with no unexpected safety concerns. This approach might be beneficial where horse-ATG is not available or not tolerated.
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
- 是
入选标准
- •Newely diagnosed bone marrow aplasia Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Patients started CSA plus Eltrombopag therapy Normal cardiac, hepatic & renal functions
排除标准
- •Hypersensitivity or contraindications to eltrombopag. Cardiovascular, pulmonary, hepatic, or renal diseases. History of malignancy. Pregnant, breastfeeding. Inherited bone marrow aplasia. Secondry bone marrow aplasia Previous thromboembolic events. Previous malignancies either solid or hematologic.
研究组 & 干预措施
Cases of aplastic anemia recieving Eltrombopag
Newely diagnosed bone marrow aplasia starting treatment with Eltrombopag in adose of 50-150mg / day
干预措施: Eltrombopag (Drug)
结局指标
主要结局
Determine overall survival rate.
时间窗: 5 years
Number if years estimated to survive after treatment
Determine hematological response after 6 months
时间窗: 6 months to 5 years
Change in CBC elements after 6 months of treatment
次要结局
- Clonal evolution to myeloid malignancy or new chromosomal abnormality(Around 2 years)
- Eltrombopag efficacy in increasing platelet count(After6 months)
- Rate of relapse in patients deemed responsers at 6 months.(Around 1 year)
- Change in serum iron and ferritin over time of treatment(From 6 months to 5 years)
- Adverse effects raelated to treatment(Within 2 years)
研究者
Noha Mahmoud
Long term outcomes of eltrombopag in patients with bone marrow aplasia, Assiut university hospital insight.
Assiut University