Prospective Multi-center Randomized Controlled Low-dose Rituximab Regimens in Chinese Adult Patients With Immune Thrombocytopenia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Overall response rate at week 12
研究概览
简要总结
A comparative study with rituximab (100 mg weekly for 4 weeks and 375mg/m2 for once) shows low dose rituximab may be a useful alternative therapy in patients with ITP.The aim of this study is to compare the efficacy and tolerability of two different regimens of low doses rituximab for the treatment of adult patients with ITP.
详细描述
This is a multicentre, prospective, open-label, randomised controlled trial. The aim of this study will compare the long-term efficacy and safety of two low-dose rituximab regimens in adult Chinese patients with glucocorticoid-resistant/dependent or relapsed ITP. Group A will receive rituximab100 mg weekly for four weeks, and group B will receive rituximab 375 mg/m2 once. After initiating treatment, if the patient has at least two consecutive evaluations (interval >7 days) without rescue therapy and a platelet count >50×109/L, the concomitant medications such as glucocorticoids can be reduced or stopped.
Within 3 months of the last rituximab dose, rescue therapy is recommended if the patient has an extremely low platelet count and an obvious bleeding tendency. Rescue therapy is limited to IVIG (0.4 g/kg per day for 3-5 days) and glucocorticoid (methylprednisolone 0.8 mg/kg per day for 7-14 days or equivalent dose of other glucocorticoids).
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
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-60 years old;
- •Diagnosis of primary immune thrombocytopenia according to the guidelines of American Society of Hematology for at least 3 months before inclusion;
- •Platelet count <30×109/L (measured at least twice during the screening, with at least a 1-week interval);
- •Failed or dependent on or relapsed after previous treatment with glucocorticoid;
- •If on glucocorticoid maintenance therapy, dose ≤0.5 mg/kg prednisone or equivalent and stabilised for at least 4 weeks;
- •Drugs such as azathioprine, danazol, cyclosporine A, tacrolimus, and sirolimus stopped for at least 4 weeks;
- •Splenectomy more than 6 months previously;
- •Previous rescue therapy of ITP (including methylprednisolone, platelet transfusion and IVIG) completed at least 2 weeks before the first administration;
- •Liver and kidney function (including alanine aminotransferase, aspartate aminotransferase, total bilirubin, serum creatine, urea nitrogen, etc.) less than 1.5 times the upper limit of normal value;
- •Eastern Cooperative Oncology Group performance status ≤2;
- •Cardiac function classification (New York Heart Association) ≤2;
- •Understand the research procedure and voluntarily sign a written informed consent form.
排除标准
- •Patients with secondary thrombocytopenia (including myelodysplastic syndrome, aplastic anemia, common variant immunodeficiency disease, hereditary thrombocytopenia, drug-induced thrombocytopenia, pseudothrombocytopenia, connective tissue disease secondary thrombocytopenia, thrombocytopenia after liver disease, etc.);
- •Previous treatment of RTX or allergic to RTX;
- •Uncontrollable primary diseases of important organs (including malignant tumor, liver failure, heart failure, kidney failure and other diseases);
- •HIV-positive status;
- •Active infection including hepatitis B (HBV), hepatitis C (HCV) and other viral antigens or DNA, RNA positive; cytomegalovirus, Epstein-Barr virus, syphilis chronic or active infection. If HBV core antibodies are positive, HBV-DNA testing is required.
- •Extensive and severe bleeding, such as hemoptysis, upper gastrointestinal hemorrhage, intracranial hemorrhage, etc.
- •Heart disease or arrhythmia need treatment, or poorly controlled hypertension;
- •Thrombotic diseases including pulmonary embolism, thrombosis, atherosclerosis, etc.;
- •Previously allogeneic stem cell transplantation or organ transplantation;
- •Mental disorders who are unable to obtain informed consent normally and participate in trials and follow-up;
- •Symptoms of toxicity from pre-trial treatment have not resolved;
- •Other severe conditions that may limit participation in the trial (e.g., diabetes; severe cardiac insufficiency; myocardial infarction or unstable arrhythmia or unstable angina within the last 6 months; gastric ulcer; active autoimmune diseases, etc.);
- •Sepsis or other irregular bleeding;
- •Taking antiplatelet drugs;
- •pregnancy, suspected pregnancy (urine human chorionic gonadotropin positive during screening) or lactation.
研究组 & 干预措施
Rituximab A group
375mg/m2 for once
干预措施: Rituximab (Drug)
Rituximab B group
100mg/week for four weeks
干预措施: Rituximab (Drug)
结局指标
主要结局
Overall response rate at week 12
时间窗: Patients will be followed for 6 months at least after Rituximab treatment.
Overall response rate was defined as proportion of subjects with a platelet count ≥ 30 × 10\^9/L and at least twice the baseline platelet count without bleeding and subjects with a platelet count ≥ 100 × 10\^9/L without bleeding at week 12 after initial administration in absence of rescue therapy, and without having had dose increment of corticosteroids during the study period.
次要结局
- Time to response (TTR)(6 months)
- Sustained response rate over 6 months and 1, 2, 3, 4, and 5 years after RTX initiation(Patients will be followed for 6 months at least after Rituximab treatment.)
- Number of subjects with clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale(3 months)
- Adverse events assessment(12 months)
研究者
Renchi Yang
Thrombosis and Hemostasis Center
Institute of Hematology & Blood Diseases Hospital, China