ATG Combined With Cyclophosphamide And Cord Blood Transfusion in Treating Patients With Severe Aplastic Anemia

Study Overview
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Brief Summary
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To assess whether ATG Combined With Cyclophosphamide and cord blood infusion can accelerate hematopoietic reconstruction in severe aplastic anemia patients and improve clinical curative effect and safety

Detailed Description
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Aplastic Anemia( AA), is a set of bone marrow hematopoietic dysfunction caused by a variety of causes, with hyperplasia of bone marrow hematopoietic cells to reduce whole blood cells and peripheral blood at the characteristics of clinical main performance for anemia, bleeding and infection. According to the severity of the bone marrow failure and the progress of the clinical course ,it is divided into Severe Aplastic Anemia (SAA) and the Non - Severe Aplastic Anemia (NSAA).Severe Aplastic Anemia can be divided into two categories: Very Severe Aplastic Anemia (VSAA) and Severe Aplastic Anemia (SAA), with the characteristics of rapid progress, refractory, poor prognosis, high mortality .The natural course is six months or so, and most patients die in a year . Hematopoietic stem cell transplantation and immunosuppressive therapy are two main treatment . The former is by far the only possible cure. It is recommended as first-line treatments, if patients have a matched sibling donor. The recommended age limit is 40 years old. But for those who have no sibling donor or patients older than 40 years old, it is recommend the immunosuppressive therapy. The investigators have already summarized the effectiveness of rabbit antithymocyte immunoglobulin (ATG), cyclophosphamide (Cy) and cyclosporine, A (CsA) and the combination of the umbilical cord blood infusion for SAA/VSAA patients without suitable donor, with short duration, without long-term immunosuppressive therapy history. The total effectiveness rates has improved to 88%, with shorter immunosuppressive maintaining therapy , rapid hematopoietic reconstruction, fewer complications. The aim of this study is to further explore whether this solution can accelerate hematopoietic reconstruction of SAA/VSAA patients and its clinical curative effect and security. This study scheme has been approved by the Jinan military region general hospital medical ethics committee.

Official Title
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Multi-center Clinical Study of Immunosuppressants, Cyclophosphamide, And Cord Blood Transfusion in Treating Patients With Severe Aplastic Anemia

Conditions
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Aplastic Anemia

Intervention / Treatment
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* Drug: Rabbit ATG, (Genzyme)
* Drug: Cy
* Drug: CsA
* Biological: Cord blood


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ,under the age of 60. Diagnosis of SAA and VSAA in accordance with the <aplastic anemia, diagnosis and treatment expert consensus> Camitta standard (see appendix 1). Confirmed of heavy and very heavy aplastic anemia within 6 months. No obvious abnormal liver and kidney function: ALT, AST,≤2.5 times the upper limit of normal , serum Creatinine and BUN ≤1.25 times the upper limit of normal Clear understanding, voluntary to participate in the study, and signed informed consent document by the patient or the legal guardian Willingness and ability to comly with the treatment plan, follow-up and laboratory tests as required Exclusion Criteria: Congenital aplastic anemia Pregnancy or breastfeeding Participated in other clinical trials within three months Presence of Any fatal disease, including respiratory failure, heart failure, liver or kidney failure, et al Aplastic anemia caused by the treatment of other malignant tumor treatment With severe mental illness With other malignant tumor Severe infection or the infection difficult to be controlled Received ATG or cyclosporine A within six months Severely allergic to biological agents Any other situation judged by the investigator that the patients inappropriate for entry into this study

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATG, Cy and cord blood transfusion group<br>ATG 3mg/kg/d for 5 days Cy 50mg/kg/d for 2 days CSA Started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-400ng/ml One unit of cord blood having no more than 3 HLA-A,B and DRB1 mismatches is transfused 24h after last dose of ATG administration. Intervention: Drug: Rabbit ATG, Thymoglobuline (Genzyme) plus Cyclophosphamide plus CSA Biological: Cord blood transfusion | Drug: Rabbit ATG, (Genzyme)<br>* ATG is an infusion of rabbit-derived antibodies against human T cells, which is used in the prevention and treatment of acute rejection in organ transplantation and therapy of aplastic anemia<br>* Other names: Anti-thymoeyteGlobulin;Drug: Cy<br>* Cyclophosphamide is a medication mainly used in chemotherapy. It is an alkylating agent of the nitrogen mustard type<br>* Other names: Cytophosphane;Drug: CsA<br>* CsA is an immunosuppressant drug widely used in organ transplantation to prevent rejection. It reduces the activity of the immune system by interfering with the activity and growth of T cells<br>* Other names: Cyclosporine;Biological: Cord blood<br>* Cord blood is blood that remains in the placenta and in the attached umbilical cord after childbirth. Cord blood is collected because it contains stem cells, which can be used to treat hematopoietic and genetic disorders<br>* Other names: Umbilical cord blood;|
| Active Comparator: ATG and CSA group<br>ATG 3mg/kg/d for 5 days CSA started from 5mg/kg/d and adjusted to maintain trough serum concentration of 200-400ng/ml Intervention: Drug: Rabbit ATG, Thymoglobuline (Genzyme) plus CSA | Drug: Rabbit ATG, (Genzyme)<br>* ATG is an infusion of rabbit-derived antibodies against human T cells, which is used in the prevention and treatment of acute rejection in organ transplantation and therapy of aplastic anemia<br>* Other names: Anti-thymoeyteGlobulin;Drug: CsA<br>* CsA is an immunosuppressant drug widely used in organ transplantation to prevent rejection. It reduces the activity of the immune system by interfering with the activity and growth of T cells<br>* Other names: Cyclosporine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The total response rate | Response rate is the ratio of CR and PR patients to all evaluated patients at the time point. CR,PR,NR and relapse is evaluated according to the guidelines for the diagnosis and management of adult aplastic anaemia from British Committee for Standards in Haematology (BCSH) | Every 3 months to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutrophil recovery time | The neutrophil recovery day is defined from day 0 until the ﬁrst of 3 consecutive days during which the absolute neutrophil count (ANC) is >0.5×10^9/L, without G-CSF administration . | From day 0 until the ﬁrst of 3 consecutive days | 
| Infection rates |  | 1 year | 
| Overall survival |  | 2 years | 
| Treatment related mortality |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cyclophosphamide, Umbilical Cord Blood, ATG