The Combination of Low-dose Rituximab and All-trans Retinoic Acid as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia: a Multicenter, Randomized, Open-label Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 168
- 试验地点
- 4
- 主要终点
- overall response
研究概览
简要总结
Randomized, open-label, multicentre study to assess the efficacy and safety of the combination of low-dose rituximab and ATRA in patients with steroid-resistant/relapsed ITP.
详细描述
Immune thrombocytopenia (ITP) is a severe bleeding disorder. Approximately 2/3 of patients achieve remission from first-line therapies. However, the underlying mechanism of steroid-resistant or relapsed ITP is not well understood; thus, treatment remains a great challenge. Rituximab has been shown to partly improve the complete remission rate of ITP. All-trans retinoic acid (ATRA) has an immunomodulatory effect on haematopoiesis, making it a possible treatment option.
A multicentre prospective study was performed in non-splenectomized ITP patients who were either resistant to a standard dose of corticosteroids or had relapsed. Patients were randomized to the low-dose rituximab+ATRA and the low-dose rituximab monotherapy groups. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Interim analysis was scheduled at 50% through recruitment. Adverse events are also recorded throughout the study, in order to assess the efficacy and safety of the combination of low-dose rituximab and ATRA in patients with steroid-resistant/relapsed ITP.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ITP confirmed by excluding other supervened causes of thrombocytopenia;
- •Platelet count of less than 30×10^9/L at enrollment;
- •Patients who did not achieve a sustained response to treatment with full dose corticosteroids for a minimum duration of 4 weeks or who relapsed during steroid-tapering or after its discontinuation;
排除标准
- •Secondary immune thrombocytopenia (e.g., patients with HIV, HCV, Helicobacter pylori infection or patients with systemic lupus erythematosus)
- •Congestive heart failure
- •Severe arrhythmia
- •Nursing or pregnant women
- •Aspartate aminotransferase and alanine transaminase levels ≥ 3×the upper limit of the normal threshold criteria
- •Creatinine or serum bilirubin levels each 1•5 times or more than the normal range
- •Active or previous malignancy
- •Patients with other diseases were undergoing treatment with immunosuppressants
- •Patients with ITP had received rituximab
研究组 & 干预措施
low-dose rituximab & ATRA
rituximab 100mg once weekly for 6 weeks and oral all-trance retinoid acid 20mg/m^2 qd for 12 weeks.
干预措施: Rituximab (Drug)
low-dose rituximab & ATRA
rituximab 100mg once weekly for 6 weeks and oral all-trance retinoid acid 20mg/m^2 qd for 12 weeks.
干预措施: All-trans retinoic acid (Drug)
low-dose rituximab
rituximab 100mg once weekly for 6 weeks
干预措施: Rituximab (Drug)
结局指标
主要结局
overall response
时间窗: From the start of study treatment (Day 1) up to the end of Year 1
The number of participants (responders) with platelet count \>=30x10\^9/L and at least a 2-fold increase in the baseline count (PR) or a platelet count \>=100x10\^9/L (CR) and the absence of bleeding, without rescue medication at 1-year follow-up. Interim analysis was scheduled at 50% through recruitment.
sustained response
时间窗: From the start of study treatment (Day 1) up to the end of Year 1
The number of participants that can maintain the platelet count \> 30 x 109/L, an absence of bleeding events, and without requirement for any other ITP-specific treatment for 6 consecutive months after achievement of response. Interim analysis was scheduled at 50% through recruitment.
次要结局
- time to response(From the start of study treatment (Day 1) up to the end of Year 1)
- incidence of adverse events(From the start of study treatment (Day 1) up to the end of Year 1)
- Initial response(From the start of study treatment (Day 1) up to the end of Week 4)
- complete response(From the start of study treatment (Day 1) up to the end of Year 1)
- duration of response(From the start of study treatment (Day 1) up to the end of Year 1)
研究者
Xiao-hui Zhang
Professor
Peking University People's Hospital