Consolidation Therapy With Alemtuzumab (MabCampath®) in Patients With Chronic Lymphocytic Leukemia Who Are in Complete or Partial 2nd Remission After Cytoreduction With Fludarabine or Fludarabine Plus Cyclophosphamide or Fludarabine Plus Cyclophosphamide Plus Rituximab or Bendamustine or Bendamustine Plus Rituximab - a Phase I/II Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 12
- 主要终点
- Dose-limiting toxicity
研究概览
简要总结
RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them.
PURPOSE: This phase I/II trial is studying the side effects and best dose of alemtuzumab in treating patients with B-cell chronic lymphocytic leukemia.
详细描述
OBJECTIVES:
- To determine the safest dose of alemtuzumab as consolidation therapy in patients in second remission after fludarabine phosphate alone; fludarabine phosphate and cyclophosphamide; fludarabine phosphate, cyclophosphamide, and rituximab; bendamustine hydrochloride alone; or bendamustine hydrochloride and rituximab.
- To determine the frequency of cytomegalovirus reactivations or infections during or after alemtuzumab treatment.
- To determine which dose of alemtuzumab is efficient to eliminate minimal residual disease in peripheral blood and bone marrow (i.e., to turn a clinical partial remission into a clinical complete remission [CR], to turn a flow cytometry-positive CR into a flow cytometry-negative CR, or to turn a PCR-positive CR into a PCR-negative CR).
- To determine the pharmacokinetic profile of alemtuzumab.
- To compare the pharmacokinetic profile between intravenous versus subcutaneous administration of alemtuzumab.
OUTLINE: This is a multicenter, dose-escalation study of alemtuzumab.
- Group 1: Patients receive escalating doses of alemtuzumab IV over 2 hours once weekly for 8 weeks until the maximum tolerated dose (MTD) is determined.
- Group 2: Patients receive escalating doses of alemtuzumab subcutaneously once weekly for 8 weeks, beginning with the MTD determined in group 1 until a second MTD is determined.
Patients undergo bone marrow and blood sample collection periodically for laboratory and pharmacokinetic studies. Samples are analyzed for minimal residual disease and T-cell subsets (i.e., CD4 and CD8) via quantitative-PCR analysis and flow cytometry and cytomegalovirus antigens via PCR.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- 未提供
排除标准
- 未提供
结局指标
主要结局
Dose-limiting toxicity
时间窗: 28 days after the last dose of study medication
• Dose-limiting toxicity (DLT) and maximal tolerable dose (MTD) DLT is defined as a) all grade III/IV non-hematologic toxicity and b) all grade IV hematologic toxicity lasting for more than 2 weeks (excluding lymphopenia) occuring during or within 4 weeks after end of consolidation therapy.
Maximum tolerated dose
时间窗: 28 days after the last dose of study medication
• Dose-limiting toxicity (DLT) and maximal tolerable dose (MTD) DLT is defined as a) all grade III/IV non-hematologic toxicity and b) all grade IV hematologic toxicity lasting for more than 2 weeks (excluding lymphopenia) occuring during or within 4 weeks after end of consolidation therapy.
次要结局
- Rate of complete minimal residual disease response(will be tested repeatedly, first time 3 months after the last dose of study medication, last time point 24 months after last dose of study medication)
- Rate of infections (especially CMV infections and reactivations)(upt to 24 months after last dose of study medication (end of study))
- Rate of immunophenotypic remission using 4-color flow cytometry(will be tested repeatedly, first time 3 months after the last dose of study medication,)
- Rate of severe hematologic and non-hematologic side effects(28 days after the last dose of study medication)
- Overall survival(upt to 24 months after last dose of study medication (end of study))
- Progression-free survival(upt to 24 months after last dose of study medication (end of study))
- Complete remission rate(28 days after the last dose of study medication)
- Pharmacokinetics of alemtuzumab (after IV and subcutaneous administration)(up to 8 weeks during the alemtuzumab treatment)