First Line Treatment of Familiar Lymphohistiocytosis by Alemtuzumab (CAMPATH®)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Number of surviving patients until HSCT
研究概览
简要总结
The purpose of this project is to study the number of surviving patients until hematopoietic stem cell transplantation (HSCT) after first line treatment of hemophagocytic lymphohistiocytosis (HLH) by Alemtuzumab
详细描述
The hemophagocytic lymphohistiocytosis (HLH) or lymphohistiocytic activation syndrome is an inflammatory condition caused by a uncontrolled proliferation of activated lymphocytes and macrophages secreting an excess of inflammatory cytokines. Familial hemophagocytic lymphohistiocytosis (FHL) is a rare disorder of the immune system, which is invariably fatal when untreated. Treatment requires the achievement of remission of HLH prior to allogeneic hematopoietic stem cell transplantation, the only curative therapy to date.
Despite significant progress in the treatment, mortality remains high and an important number of patients will die before being eligible for HSCT.
A better understanding of the pathophysiology of FHL has opened new avenues for immunotherapy. Based on previous observations concerning the utilization of Anti-thymoglobulins (ATG) for the treatment of patients with FHL, the protocol propose a new therapeutic strategy using Alemtuzumab in association with steroids as first line treatment in FHL. This proposition is based on the hypothesis that Alemtuzumab, capable of killing T lymphocytes efficiently in vivo, should be better tolerated than ATG. In fact, in contrast to the mechanism of action of ATG, Alemtuzumab does not activate T lymphocytes.
A better tolerance and efficacy of Alemtuzumab is expected in the treatment of the hemophagocytic lymphohistiocytic syndrome. This may have a positive impact not only on survival until HSCT, but also on overall survival and quality of life with regard to long-term neurological sequelae.
This is a multicenter, open, phase I/II, non-comparative, non randomized study. Patients are recruited by the investigators during hospitalization for a first episode of lymphohistiocytic activation syndrome requiring specific treatment.
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
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
hemophagocytic lymphohistiocytosis (HLH)
Alemtuzumab (CAMPATH®)
- Initial Treatment (D1 to D3) D1: 0.5 mg / kg / day Alemtuzumab combined with 2 mg /kg/d of IV Methylprednisolone (MP) or PO Prednisolone, and IVC or PO cyclosporine (CSA) (target rate from 150 to 200 ng / ml in the absence of renal failure) D2 and D3: 1 mg / kg / day Alemtuzumab combined with 2 mg / kg / d of IV MP or PO Prednisolone and IVC or PO CSA (target rate 150-200 ng / ml)
The maximum dose of Alemtuzumab is limited to 30 mg per day (1 vial). 2. Maintenance treatment (D4 to D14)
- MP/Prednisolone progressive tapering starting at D4 (2 mg / kg / day) to reach the dose 0.5 mg / kg / day at D14
- CSA IVC or PO at a target rate of 150-200 ng / ml
干预措施: Alemtuzumab (Drug)
hemophagocytic lymphohistiocytosis (HLH)
Alemtuzumab (CAMPATH®)
- Initial Treatment (D1 to D3) D1: 0.5 mg / kg / day Alemtuzumab combined with 2 mg /kg/d of IV Methylprednisolone (MP) or PO Prednisolone, and IVC or PO cyclosporine (CSA) (target rate from 150 to 200 ng / ml in the absence of renal failure) D2 and D3: 1 mg / kg / day Alemtuzumab combined with 2 mg / kg / d of IV MP or PO Prednisolone and IVC or PO CSA (target rate 150-200 ng / ml)
The maximum dose of Alemtuzumab is limited to 30 mg per day (1 vial). 2. Maintenance treatment (D4 to D14)
- MP/Prednisolone progressive tapering starting at D4 (2 mg / kg / day) to reach the dose 0.5 mg / kg / day at D14
- CSA IVC or PO at a target rate of 150-200 ng / ml
干预措施: Methyl Prednisolone (MP) (Drug)
hemophagocytic lymphohistiocytosis (HLH)
Alemtuzumab (CAMPATH®)
- Initial Treatment (D1 to D3) D1: 0.5 mg / kg / day Alemtuzumab combined with 2 mg /kg/d of IV Methylprednisolone (MP) or PO Prednisolone, and IVC or PO cyclosporine (CSA) (target rate from 150 to 200 ng / ml in the absence of renal failure) D2 and D3: 1 mg / kg / day Alemtuzumab combined with 2 mg / kg / d of IV MP or PO Prednisolone and IVC or PO CSA (target rate 150-200 ng / ml)
The maximum dose of Alemtuzumab is limited to 30 mg per day (1 vial). 2. Maintenance treatment (D4 to D14)
- MP/Prednisolone progressive tapering starting at D4 (2 mg / kg / day) to reach the dose 0.5 mg / kg / day at D14
- CSA IVC or PO at a target rate of 150-200 ng / ml
干预措施: Cyclosporin A (CSA) (Drug)
结局指标
主要结局
Number of surviving patients until HSCT
时间窗: Day 1 until transplantation, up to 4 months
次要结局
- Number of complete remissions following treatment(Day 14, Day 21, Day 28)
- Time of delay between the first administration of Alemtuzumab and complete remission(Day 14, Day 21, Day 28)
- Dosage of Alemtuzumab(Day1-3, Day7, Day15-16, Day22-23, Day28)
- Number of side effects(Day 1 until transplantation, up to 4 months)