" Anemil Trial ": Phase I/II Clinical Trial Evaluating the Interest of Interleukine-2 for Patients With Active Warm Hemolytic Anemia Resistant to Conventional Treatment
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- Percentage of LTCD8+CD25highFoxp3+ .
研究概览
简要总结
The investigators have demonstrated that the mean percentage of circulating CD8+ regulatory T (CD8 Tregs) cells is significantly higher in patients with warm hemolytic anemia (wAHAI) in remission than in controls and is correlated to hemoglobin levels. In vitro, low dose of interleukine-2 (IL2) induce the expansion of CD8 Tregs. The objective is to demonstrate that, over a 9 week treatment period; low doses of IL2 can induce the expansion of CD8Tregs in patients with active wAHAI.
详细描述
wAIHA is a B-cell-mediated autoimmune disease in which red blood cells are targeted by autoantibodies, which leads to marked decrease in their lifespan. The investigators demonstrated two years ago in a multivariate retrospective study that the CD3+CD8+ HLA-DR+ T-cell population was associated to a better outcome. The investigators observed that the proportion of circulating CD3+CD8+CD25highFoxp3+ T cells was significantly higher in patients with wAIHA in remission than in controls and correlated to hemoglobin levels. Extensive phenotyping and functional analysis revealed that those cells were bona fide Tregs acting in an IL10-dependent manner. Finally, culture of PBMC from normal donors or active wAIHAI patients with low dose of IL2 promoted the expansion of functional CD3+CD8+CD25+Foxp3+. Those observations constituted the rationale to propose low dose of IL2 to treat patients with active wAIHA with the objective of demonstrating that this treatment is able to induce the expansion of CD8Tregs, over a 9 week treatment period.
Four courses of IL2 (aldesleukin [Proleukin, Novartis]) will be administered subcutaneously for 5 days. The first course will be limited to a dose of 1.5 million IU per day and followed by a 9 day wash-out. The other courses of 3 million IU per day will be initiated after a 16 day wash-out.
Patients will be evaluated on day 1 and day 5 of each treatment course, before the first and last administration of interleukin-2 and will also be evaluated at 6 months.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults (18 years old)
- •wAHAI defined by the presence of hemolysis and positive coombs test (IgG +/-C3)
- •Absence of infection or other hematologic disease
- •wAHAI not responding to conventional steroids despite a dose over 10 mg
- •No treatment with rituximab for a minimum of 6 months
- •Signed informed consent form
排除标准
- •Less than 18 years old
- •Cold AHAI
- •IL2 allergy
- •Chemiotherapy or immunosuppressive treatment
- •Treatment with rituximab for less than 6 months
- •Neoplasia or hematologic malignancy
- •Aplastic anemia
- •Neutropenia ≤ 1000 mm3
- •Infection
- •Hepatitis B or C
- •wAHAI associated with systemic lupus erythematosus depending on ACR criteria
- •Cardiac insufficiency
- •Hypertension
- •Pulmonary insufficiency
- •Liver cirrhosis
- •Thrombopenia below 50000/mm3
- •Drug addiction, alcohol abuse
- •Psychiatric disorder
- •Absence of signed informed consent
研究组 & 干预措施
Low doses of Interleukine-2
Low doses of Interleukine-2 over a 9 week treatment period
干预措施: Interleukine-2 (Drug)
结局指标
主要结局
Percentage of LTCD8+CD25highFoxp3+ .
时间窗: 9 weeks after inclusion
Increase of the percentage of LTCD8+CD25highFoxp3+ at the end of the IL2 treatment.
次要结局
- Incidence of complications with the treatment.(6 months after inclusion)
- Evaluation of lymphocyte sub-populations(5 days, 20 days, 40 days, 61 days, 63 days and 6 months after inclusion)
- Evaluation of lymphocyte activation.(5 days, 20 days, 40 days, 61 days, 63 days and 6 months after inclusion)
- Hemolysis as measured by hemoglobin, haptoglobin, reticulocytes and LDH levels(5 days, 20 days, 40 days, 61 days, 63 days and 6 months after inclusion)
- Dose of steroid treatment(5 days, 20 days, 40 days, 61 days, 63 days and 6 months after inclusion)