Ibritumomab Tiuxetan and High-Dose Melphalan as Conditioning Regimen Before Autologous Stem Cell Transplantation for Elderly Patients With Lymphoma in Relapse or Resistant to Chemotherapy. A Multicenter Phase I Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 10
- 主要终点
- Dose-limiting toxicity of high-dose melphalan in combination with yttrium Y 90 ibritumomab tiuxetan
研究概览
简要总结
RATIONALE: Giving chemotherapy drugs, such as melphalan, before an autologous stem cell transplant helps stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Also, monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan and rituximab, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Chemotherapy and monoclonal antibody therapy also prepares the patient's bone marrow for the stem cell transplant. Giving colony-stimulating factors, such as G-CSF, and vinorelbine helps stem cells move from the bone marrow to the blood so they can be collected and stored. The stem cells are returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and monoclonal antibody therapy.
PURPOSE: This phase I trial is studying the side effects and best dose of melphalan when given together with yttrium Y 90 ibritumomab tiuxetan and rituximab followed by autologous stem cell transplant in treating older patients with non-Hodgkin's lymphoma that has relapsed or not responded to previous treatment.
详细描述
OBJECTIVES:
- Determine the maximum tolerated dose of high-dose melphalan when given together with yttrium Y 90 ibritumomab tiuxetan and rituximab as a conditioning regimen followed by vinorelbine ditartrate- and filgrastim (G-CSF)-mobilized autologous stem cell transplantation in elderly patients with relapsed or refractory CD20-positive non-Hodgkin's lymphoma.
- Evaluate the feasibility and safety of this regimen in these patients.
- Determine the feasibility of stem cell mobilization with vinorelbine ditartrate in patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of high-dose melphalan.
- Stem cell harvest and mobilization: Patients receive vinorelbine ditartrate IV on day -36 and filgrastim (G-CSF) subcutaneously (SC) twice daily on days -33 to -29. Patients undergo peripheral blood stem cell harvest on days -29 to -26.
- Radioimmunotherapy: Patients receive rituximab IV. Within 4 hours after completion of rituximab, patients receive indium In 111 ibritumomab tiuxetan (imaging dose) IV over 10 minutes on day -25. Patients undergo assessment of biodistribution, imaging, and dosimetry on days -25, -22, and optionally on day -20. Patients with acceptable biodistribution of indium In 111 ibritumomab tiuxetan receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan (therapeutic dose) IV over 10 minutes on day -18.
- High-dose chemotherapy: Patients receive high-dose melphalan IV on day -1. Cohorts of 3-6 patients receive escalating doses of high-dose melphalan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
- Autologous stem cell transplantation (ASCT): Patients undergo ASCT on day 0. Patients receive G-CSF SC beginning on day 5 and continuing until blood counts recover.
After completion of study treatment, patients are followed for 100 days.
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
- 65 Years 至 120 Years（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
研究组 & 干预措施
Zevalin, Rituximab, Melphalan
干预措施: ibritumomab tiuxetan (Drug)
Zevalin, Rituximab, Melphalan
干预措施: rituximab (Drug)
Zevalin, Rituximab, Melphalan
干预措施: melphalan (Drug)
Zevalin, Rituximab, Melphalan
干预措施: vinorelbine tartrate / G-CSF (Drug)
Zevalin, Rituximab, Melphalan
干预措施: autologous hematopoietic stem cell harvesting and transplantation (Procedure)
结局指标
主要结局
Dose-limiting toxicity of high-dose melphalan in combination with yttrium Y 90 ibritumomab tiuxetan
时间窗: within 8 weeks after application of melphalan
次要结局
- Event occurrence up to 100 days after transplantation(up to 100 days after transplantation)
- Toxicity(100 days (+/- 5 days) after reinfusion of stem cells)
- Complete remission 100 days after transplantation(100 days after transplantation)