Randomized Trial Comparing the Efficacy of Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia,Lymphoplasmacytic Lymphoma or Splenic Marginal Zone Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 414
- 试验地点
- 1
- 主要终点
- Patient overall response
研究概览
简要总结
Waldenström's macroglobulinaemia (WM) is a lymphoproliferative disorder characterized by a monoclonal IgM paraprotein and morphological evidence of lymphoplasmacytic lymphoma: the cells are IgM+, IgD+, CD19+ and CD20+ but usually CD5-, CD10- and CD23-. The treatment efficacy is difficult to assess because of the lack of clear diagnostic criteria , good response criteria, and of randomized trials.
The actual treatment is Chlorambucil, an alkylating agent. A purine analogue such as Fludarabine has proven its efficacy on 30 % to 80 % as first line therapy
This study is a phase II b open, prospective, international multicenter trial (England, Dr Johnson, Dr Catovsky, Australia: Dr Seymour) promoted by the French Cooperative Group on Chronic Lymphoid Leukemia in untreated WM, or closely related disorders ( Lymphoplasmacytic lymphoma or splenic marginal zone lymphoma). 366 patients must be included, among them 180 patients in France. Patients will be stratified according to the lymphoproliferative disorder.
The patients will receive Chlorambucil by oral route for 10 days every 28 days (12 cycles) (8 MG/M², 6 MG/M² if patient is more than 75 years old) or Fludarabine by oral route for 5 days every 28 days (6 cycles) (40MG/M², 30 MG/M² if patient is more than 75 years old).
The primary objective is to compare the efficacy (response rate) of Chlorambucil to Fludarabine in previously untreated patients. The secondary objectives are the duration of response, the improvement of hematological parameters, the toxicity, the quality of life, the event free survival and the overall survival.
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
- •Established diagnosis of Waldenström macroglobulinemia (the 2nd Workshop on Waldenstrom's macroglobulinemia) or Lymphoplasmacytic lymphoma or Splenic Marginal Zone Lymphoma, needing a treatment
- •Life expectancy > 6 months
- •Creatinine < 200 µmol/l
- •SGPT and SGOT < 2x ULN
- •A negative direct Coombs test
- •Written informed consent
排除标准
- •Past chemotherapy/radiotherapy/immunotherapy prior to the study for Waldenström macroglobulinemia
- •Previous malignancy less than 5 years ago except carcinoma in situ of the cervix and non-melanoma skin cancer
- •Positive HIV serology
- •Active Hepatitis B or C
- •Lactation/pregnancy
- •Impossible good compliance with the study protocol
- •Active infection not controlled
- •Psychological condition hampering understanding of the study
- •Transformation into large B cell lymphoma
- •Peripheral neuropathy > grade II
研究组 & 干预措施
1
Chlorambucil 8mg/m² (6 mg/m² if patient aged more than 75 years old) 10 days every 28 days during 12 months
干预措施: Chlorambucil (Drug)
2
Fludarabine
干预措施: Fludarabine (Drug)
结局指标
主要结局
Patient overall response
时间窗: At the end of treatment whether 6 or 12 months
次要结局
- Biological study(Whether 6 or 12 months)
- Quality of life(Whether 6 or 12 months)
- Response duration(60 months)
- Treatment toxicity(60 months)
- Event free survival(60 months)
- Overall survival(60 months)