Different Doses of Sirolimus for the Treatment of Cystic Lymphatic Malformations
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- The proportion of patients achieving an objective response at month 12
研究概览
简要总结
The purpose of this study is to compare the efficacy and safety of different concentration gradients of sirolimus in the treatment of cystic lymphatic malformation.
详细描述
Cystic lymphatic malformation is a disease caused by abnormal development of the lymphatic system, characterized by abnormal dilation and/or structural disorder of lymphatic vessels. These abnormalities may lead to accumulation of lymphatic fluid, causing local swelling, pain, and even affecting organ function. Cystic lymphatic malformation can occur anywhere in the body, including skin, soft tissue, internal organs, etc.
Sirolimus, also known as rapamycin, is an immunosuppressant mainly used to prevent rejection after organ transplantation. In recent years, studies have shown that sirolimus has certain potential in the treatment of lymphatic malformations.
However, long-term high-dose sirolimus treatment can cause some common complications, such as oral mucositis, which affects the quality of life of patients. More fine-grained control of rapamycin plasma concentrations may help improve the therapeutic effect and reduce the incidence of complications. Therefore, the investigators conducted this study to understand whether low-dose rapamycin is beneficial to the prognosis of patients.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Presenting a LM with the following characteristics:
- •Male and female;
- •Between 0 and 18 years of age;
- •LM diagnosis was confirmed by local investigators and by consensus of our multidisciplinary vascular anomaly group at the West China Hospital of Sichuan University based on:
- •Biopsy; Compatible MRI findings; History and clinical features.
排除标准
- •Patients contraindicated for the administration of sirolimus (e.g., those with an allergy to sirolimus or other rapamycin analog)
- •Exposure to chemotherapy, embolization, corticosteroids, propranolol, sclerotherapy or any other investigational agents within 1 weeks before enrolment on study;
- •Patients had a history of a major surgery within 2 weeks before enrollment;
- •Patients who have a history of treatment with sirolimus or other mTOR inhibitor;
- •Any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of enrollment;
- •Concurrent severe and/or uncontrolled medical diseases that could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal tract ulceration).
- •Impairment of gastrointestinal function or chronic gastrointestinal disease that may significantly alter the absorption of sirolimus.
- •Patients with inadequate liver function:
- •Total bilirubin higher than or equal to 1.5 × the upper limit of the normal (ULN) for age and alanine aminotransferase and aspartate aminotransferase higher than or equal to 2.5 × the ULN for age.
- •Patients with inadequate renal function:
- •0-5 years of age maximum serum creatinine (mg/dL) of 0.8; 6-10 years of age maximum serum creatinine (mg/dL) of 1.0; 11-14 years of age maximum serum creatinine (mg/dL) of 1.2;
- •Adequate bone marrow function:
- •Absolute neutrophil count lower than 1 × 109/L;
- •History of a malignancy within 5 years;
- •HIV infection or known immunodeficiency;
- •Indication for treatment with corticosteroids, vincristine, interferon-α, sirolimus, or tacrolimus for an indication other than IH;
- •Patients with an inability to participate in or follow-up during the study treatment and assessment plan;
- •Inability to give informed consent.
研究组 & 干预措施
Low dose of sirolimus
The plasma trough concentration of sirolimus is maintained within the range of 5-8 ng/ml by adjusting sirolimus dose, for 1 year.
干预措施: Sirolimus (RAPAMUNE) (Drug)
High dose of sirolimus
The plasma trough concentration of sirolimus is maintained within the range of 10-15 ng/ml by adjusting sirolimus dose, for 1 year.
干预措施: Sirolimus (RAPAMUNE) (Drug)
结局指标
主要结局
The proportion of patients achieving an objective response at month 12
时间窗: 12 months
Objective response was defined as ≥20% reduction in LM volume compared to that at baseline.
次要结局
- The proportion of patients achieving an objective response at month 6(6 months)
- lesion responses(6 and 12 months)
- Quality of life (QOL) in patients(12 months)
- Disease sequelae(12 months)
- Frequency of adverse events(12 months)