Study of Human Umbilical Cord-derived Mesenchymal Stem Cells for Treatment of Refractory Immune Thrombocytopenia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Changes of the platelet counts after hUC-MSCs infusion
研究概览
简要总结
Primary Objective: To evaluate the safety and efficacy of human umbilical cord-derived mesenchymal stem cells（hUC-MSCs） to treat refractory immune thrombocytopenia（ITP）.
Secondary Objective: To observe the changes of immune function in refractory ITP patients with human umbilical cord-derived mesenchymal stem cells（hUC-MSCs） after infusion, and to explore and reveal the mechanism of hUC-MSCs in treating ITP.
详细描述
Human umbilical cord (hUC)-derived mesenchymal stem cells (MSCs) have been shown to have marked therapeutic effects in a number of inflammatory diseases and autoimmune diseases in humans based on their potential for immunosuppression and their low immunogenicity. Currently, no more data is available on the safety and effectiveness of hUC-MSCs to treat immune thrombocytopenia patients.
This is a single-arm study to evaluate the safety and efficacy of hUC-MSCs to treat refractory immune thrombocytopenia（ITP）. In addition, it is the objective of this study to observe the changes of immune function in refractory ITP patients after hUC-MSCs infusion, and to explore and reveal the mechanism of hUC-MSCs in treating ITP.
The investigator will assess the changes of the platelet counts after hUC-MSCs infusion from week 1 to week 28, and observe incidence of adverse events during and after hUC-MSCs infusion.The investigator will complete virus detection( including HBV, HCV, HIV, Syphilis, etc) at week 4 and week 16 after hUC-MSCs infusion.
The dose of hUC-MSCs will be successively divided into three increasing dose(group A: hUC-MSCs 0.5×10^6/kg, weekly for 4 weeks, 3 patients; group B: hUC-MSCs 1.0×10^6/kg, weekly for 4 weeks, 3 patients; hUC-MSCs 2.0×10^6/kg, weekly for 4 weeks, 3 patients) with 3 patients in each group according to the dose.
The principle of increasing dose will be carried out successively from low dose to high dose group. According to the results of the safety and efficacy data from these 9 patients, the investigator will determine one of the doses and expand the sample size to 6 cases.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 60 years old, male or female;
- •Conform to the diagnostic criteria of immune Thrombocytopenia (ITP);
- •Three months after splenectomy;
- •The first-line treatment drugs such as human immunoglobulin, glucocorticoid, and the second-line treatment of thrombopoietin drugs and rituximab were invalid, or there was no response or recurrence after splenectomy;
- •Diagnosis of ITP>6 months；
- •More than 3 months after rituximab treatment；
- •Platelet counts <30 ×10^9/L, and bleeding tendency;
- •People who are willing to sign the informed consent voluntarily and follow the research program.
- •Subject is practicing an acceptable method of contraception. Women of childbearing potential must have a negative serum pregnancy test in the whole study;
排除标准
- •ECOG score standard >2；
- •Secondary thrombocytopenic purpura;
- •Patients with poor compliance;
- •Positive serology for HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), and/or hepatitis D virus (HDV), Syphilis; Positive for Epstein-Barr Virus DNA, Cytomegalovirus DNA;
- •Pregnancy or lactation period;
- •History of thrombosis;
- •The serum chemistry results exceed the upper laboratory normal range by more than 20%, such as ALT, AST, TBIL, BUN, Cre etc;
- •Pre-existing cardiac disease, including congestive heart failure of New York Heart Association [NYHA] Grade III/IV, arrhythmia requiring treatment or myocardial infarction within the last 6 months. No arrhythmia known to increase the risk of thrombotic events (e.g. atrial fibrillation), or patients with a QT >450msec or QTc > 480 for patients with a Bundle Branch Block;
- •History of solid organ or bone marrow transplant;
- •Researchers believe that patients should not participate in the test of any other condition.
结局指标
主要结局
Changes of the platelet counts after hUC-MSCs infusion
时间窗: 28 weeks
The investigator will assess the changes of the platelet counts after hUC-MSCs infusion from week 1 to week 28.
Incidence of adverse events after hUC-MSCs infusion
时间窗: 4 weeks
The investigator will observe incidence of adverse events during and after hUC-MSCs infusion, including fever, thrombosis, diarrhea, skin rash and so on.
Changes in virus safety indicators after hUC-MSCs infusion
时间窗: 16 weeks
The investigator will complete virus detection( including HBV, HCV, HIV, Syphilis, EB, CMV, etc) at week 4 and week 16 after hUC-MSCs infusion.
次要结局
- Changes of antibody production of hUC-MSCs in peripheral blood(24 days)
- Changes of concentration of hUC-MSCs in peripheral blood(96 hours)
- Changes of immune function in refractory ITP patients after hUC-MSCs infusion(28 weeks)