Randomized Clinical Trial of the Use of & Cyclosporine in Children With Sever Idiopathic Aplastic Anemia
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Changes in hemoglobin count (at Baseline, 26 Weeks and up to 52 week)
研究概览
简要总结
Aplastic anemia is a rare disorder characterized by pancytopenia and a hypo cellular bone marrow.but,It is very serious disease causing morbidity and mortality.
Aplastic anemia can be treated effectively with haematopoietic stem cell transplantation and immunosuppressive drug regimens but haematopoietic stem cell transplantation has limitations due to its cost and many patient are unsuitable. Immunosuppressive drug has a significant number of patients have persistent cytopenias. Currently, the treatment of these patients is regular transfusion, which are expensive, inconvenient, and associated with serious side effects related to iron overload and transfusion.
Eltrombopag is an oral thrombopoietin mimetic that selectively binds at the transmembrane and juxtamembrane domains of the thrombopoietin receptor, at sites distinct from the binding site of thrombopoietin therefore it does not compete for binding with the native molecule. It promoting thrombopoiesis and release of platelets from mature megakaryocytes. Also, promote other hematopoietic stem cell as well as in thrombopoiesis .
详细描述
Aplastic anemia is a rare disorder characterized by pancytopenia and a hypo cellular bone marrow.This causes a deficiency of all three blood cell types (pancytopenia): red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia) . The clinical consequences are anemia, usually with a requirement for frequent red blood cell transfusions, life-threatening bleeding from thrombocytopenia, and infection because of neutropenia. Bacterial and fungal infections are most common and are a significant cause of morbidity and mortality.
The incidence of acquired Aplastic anemia in Europe and North America is around two per million children per year . The incidence is 2-3 times higher in East Asia. There is no significant difference in incidence between males and females .
The pathogenesis of Aplastic anemia is complex and involves an abnormal hematopoietic microenvironment, hematopoietic stem cell/progenitor cell deficiencies and immunity disorders. The etiological basis for marrow failure includes primary defects in or damage to the stem cell or the marrow microenvironment. The distinction between acquired and inherited disease may present a clinical challenge, Congenital or inherited causes of Aplastic anemia are responsible for at least 25% of children with this condition and for perhaps up to 10% of adults. Acquired causes of Aplastic anemia form (80%) of cases, include Idiopathic (> 80 %), Post-infectious 15% (particularly after hepatitis 9%, Epstein-Barr virus , human immune deficiency virus, parvovirus, and mycobacteria, Drug-induced and toxins (4%).
Definitive and potentially curative therapy with haematopoietic stem cell transplantation However, only a minority (30 %) of patients have a suitable donor. Immunosuppressive therapy with horse or rabbit antithymocyte globulin plus cyclosporine is the most commonly used alternative treatment in about two thirds of cases. Response is associated with a favorable long-term outlook. 30 -40% of patients are refractory to immunosuppressive therapy and remain pancytopenic after therapy. Even patients that respond to immunosuppressive therapies with an improvement in their life-threatening neutropenia sometimes have persistent thrombocytopenia .
Aplastic anemia can be treated effectively with haematopoietic stem cell transplantation and immunosuppressive drug regimens but haematopoietic stem cell transplantation has limitations due to its cost and many patient are unsuitable. Immunosuppressive drug has a significant number of patients have persistent cytopenias. Currently, the treatment of these patients is regular transfusion, which are expensive, inconvenient, and associated with serious side effects related to iron overload and transfusion.
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
- None
入排标准
- 年龄范围
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Current diagnosis of sever Aplastic anemia
- •Diagnosis of sever Aplastic anemia is established if Bone marrow cellularity <25% or and at least two of the following criteria are met:- (i) absolute neutrophil count less than 0.5 × 109/L, (ii) platelet count less than 20 × 109/L, and (iii) reticulocyte count less than 20 × 109/L
- •No, evidence of viral or drug suppression of the marrow, dysplasia, or underproduction anemias secondary to B12, folate, iron or other reversible causes.
- •Age equal to 1 years old to 18 years old
- •Written informed consent signed by a parent or legal guardian prior to initiation of any study specific procedure.
- •Hematopoietic stem cell transplantation is not available or suitable as a treatment option or has been refused by the patient.
- •Bone marrow aspirate and biopsy at any time during the 4 weeks prior to first dose of eltrombopag
排除标准
- •Prior and/or active medical history of:-
- •Fanconi anemia (via chromosomal breakage test or growth arrest by flow cytometry). Other known underlying congenital/inherited marrow failure syndromes.
- •Symptomatic Paroxysmal Nocturnal Hemoglobinuria
- •Other known or suspected underlying primary immunodeficiency
- •Any malignancy
- •Active infection not responding to appropriate therapy
- •Any out of range lab values Creatinine >2.5 mg/dL× the upper limit of normal, Total bilirubin >1.5 × the upper limit of normal mg/dL ,Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 × the upper limit of normal
- •Hypersensitivity to eltrombopag or its components
- •Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient's ability to tolerate protocol therapy, or that death within 7-10 days is likely.
研究组 & 干预措施
case arm
cyclosporine plus an oral dose of Eltrombopag
干预措施: Eltrombopag (Drug)
结局指标
主要结局
Changes in hemoglobin count (at Baseline, 26 Weeks and up to 52 week)
时间窗: 52 week
measuring the following: Increase from baseline by 1.5 gram g/dL or more when the baseline hemoglobin level is \<8.5 g/dL and no red blood cell (RBC) transfusion at baseline. A decrease of at least four units in RBC transfusions in the post-treatment 8-week period compared to the pre-treatment 8-week period..
changes in absolute Neutrophil count (at Baseline, 26 Weeks and up to 52 week)
时间窗: 52 week
measuring the increase in the absolute neutrophil count of more than 500 per cubic millimeter
complete response (CR) - 12 month
时间窗: 52 weeks
CR defined as all three parameters meet the following criteria : Hb ≥100 g/l, platelet count ≥100 × 109/L, and ANC ≥1 × 109/L. Additionally, patients had to be transfusion and growth factor independent
Partial response (PR) - 12 month
时间窗: 52 weeks
PR was defined as blood count no longer meeting Camitta criteria for severs aplastic anemia in case of sever aplastic anemia (SAA): Absolute neutrophil count (ANC) \>500/μL Platelet count \>20 000/μL Reticulocyte count \>20 000/μL
changes in Platelet count (at Baseline, 26 Weeks and up to 52 week)
时间窗: 52 week
increase of platelet count from baseline by 20,000/microliter or more (in the absence of platelet transfusion), or independence from platelet transfusions for a minimum of 8 weeks in patients who were previously transfusion-dependent.
次要结局
- Overall hematologic response (CR + PR) rate - 6 month(26 week)
- The hematological responses(up to to 52 week)
- complete response (CR)- 6 month(26 week)
- The toxicity(Up to 30 days after last dose of study treatment)
- Partial response (PR) - 6 month(26 week)
- Overall hematologic response (CR + PR) rate - 12 month(52 week)
研究者
Mai Ali Abdelfatah Ahmed
assistant lecturer
Assiut University