A Prospective, Randomized, Multicenter Clinical Trial of Acquired Haemophilia A With Steroid Combined With Cyclophosphamide Versus Steroid Combined With Rituximab
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Proportion of inhibitor eradication and time to attain first remission
研究概览
简要总结
Purpose:
To evaluate the efficacy when administering steroid combined with single dose rituximab to eliminate the antibody in acquired hemophilia A patients compared to treatment using steroid with cyclophosphamide.
The study will test the hypothesis that steroid combined with small dose rituximab is as effective as steroid combined with cyclophosphamide for FVIII inhibitor eradication in Chinese patients with acquired hemophilia A.
Study design Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment
详细描述
This is a prospective randomized multi-center controlled pilot trial comparing the regimen of steroid with rituximab and steroid with cyclophosphamide to eradicate anti-factor VIII antibodies in Chinese patients with acquired hemophilia A.
Patients will be randomized to two regimens: methylprednisolone 0.8mg/kg/day (or equivalent corticosteroid doses) for 3 weeks (then tapering gradually,8 weeks in total) with rituximab (375mg/m2 for one dose) or methylprednisolone 0.8mg/kg/day (or equivalent corticosteroid doses) for 3 weeks (then tapering gradually,8 weeks in total) with cyclophosphamide 2mg/kg/day until inhibitor negative(no longer than five weeks).
Patients will be randomized to the treatment cohorts according to the biostatistical methods.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18-80 years old
- •Men or women
- •Women post-menopausal or with ongoing contraception
- •Diagnosis of acquired hemophilia A
- •Patient must be insured
- •Patient has provided written informed consent prior to enrollment
- •Patient compliant
排除标准
- •Congenital hemophilia
- •Ongoing treatment with prednisone > 20mg/d （or equivalent corticosteroid doses） more than 1 month
- •Ongoing treatment with prednisone >0.7mg/kg（or equivalent corticosteroid doses） more than 10 days
- •Pregnant and breastfeeding women
- •Allergy to steroid
- •Immunosuppressive agents treatment within 30 days
- •Serum transaminase and bilirubin greater than 1.5 times the upper limit of normal value
- •Hepatitis B surface antigen or hepatitis C antibody or HIV antibody (I + II) or syphilis antibody positive
- •Patients with diabetes, hypertension, glaucoma, peptic ulcer, herpes zoster, pulmonary infection and so on, who should not be treated with glucocorticoids
- •Patients with poor compliance
- •Those who can not take contraceptive measures during the test period
- •Patient who is considered by the investigator not suitable for clinical study
- •Thrombocytopenia
- •Leucocytopenia
研究组 & 干预措施
Steroid+Rituximab
Methylprednisolone 0.8 mg/kg/day (or equivalent corticosteroid doses) for 3 weeks（then tapering gradually, 8 weeks in total）+Rituximab 375mg/m2 for one dose.
干预措施: Steroid (Drug)
Steroid+Rituximab
Methylprednisolone 0.8 mg/kg/day (or equivalent corticosteroid doses) for 3 weeks（then tapering gradually, 8 weeks in total）+Rituximab 375mg/m2 for one dose.
干预措施: Rituximab (Drug)
Steroid +Cyclophosphamide
Methylprednisolone 0.8 mg/kg/day (or equivalent corticosteroid doses) for 3 weeks （ then tapering gradually, 8 weeks in total）+ Cyclophosphamide 2 mg/kg/day until inhibitor negative (no longer than five weeks)
干预措施: Steroid (Drug)
Steroid +Cyclophosphamide
Methylprednisolone 0.8 mg/kg/day (or equivalent corticosteroid doses) for 3 weeks （ then tapering gradually, 8 weeks in total）+ Cyclophosphamide 2 mg/kg/day until inhibitor negative (no longer than five weeks)
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Proportion of inhibitor eradication and time to attain first remission
时间窗: During 18 months
The proportion of patients achieving complete remission (CR) defined as titer FVIII inhibitor lower than 0.6 Bethesda unit, factor VIII level\> 50% and no bleeding events without bypass treatments for 24 hours and the time to attain first remission will be evaluated.
次要结局
- Relapse rate and time to relapse(During 18 month)
研究者
Zhang Lei, MD
vice Director of Thrombosis and Hemostasis Center
Institute of Hematology & Blood Diseases Hospital, China