A Phase I Study of Bexxar® (Tositumomab and 131I-Tositumomab) Radioimmunotherapy in Patients With Relapsed or Residual CD20 Antigen-Expressing B-Cell Lymphomas Following Autologous Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- dose-limiting toxicity
研究概览
简要总结
Patients with B-cell lymphoma who relapse after autologous transplant tend to have a poor prognosis. Currently, there is no standard treatment for such patients. Bexxar is a radioactive antibody therapy that has shown a 60-80% response rate in non-transplanted patients with relapsed B-cell lymphoma. This study will test the safety and efficacy of Bexxar in the treatment of patients whose B-cell lymphoma has relapsed after an autologous transplant.
详细描述
High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become the standard of care for relapsed/refractory chemotherapy-sensitive non-Hodgkin's lymphomas (NHL). However, one-half to two-thirds of such patients will relapse after ASCT, with subsequent poor prognosis, and new therapies are urgently needed for this patient population. Radioimmunotherapy (RIT) as a single agent therapy in patients with CD20 antigen-expressing relapsed or refractory low-grade, follicular, or transformed NHL has demonstrated overall response rates of 60-80% and has been approved by the FDA for use in this setting. While RIT is currently under investigation as a component of conditioning regimens for ASCT, the safety and efficacy of RIT after ASCT has not yet been well described. We will conduct a single-center Phase I dose-escalation trial of Bexxar (Tositumomab and 131I Tositumomab) for treatment of relapsed or residual CD20 antigen-expressing B-cell lymphomas following ASCT. Our primary aim will be to determine the safety, dose-limiting toxicity, and maximum tolerated dose of Bexxar in this post-ASCT patient population. Our secondary aim will be to describe the overall response rate, progression-free survival, time to treatment failure, and overall survival. Should Bexxar prove to be safe in this population, subsequent trials will be designed to investigate further the efficacy of RIT in the post-transplant setting.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •CD20 positive B-cell lymphoma
- •Confirmed relapsed/refractory disease following autologous transplant
- •Age ≤ 75 years
- •Performance status 0 or 1
- •Creatinine ≤ 1.5 or calculated creatinine clearance ≥ 60 ml/min
- •Total bilirubin, AST, and ALT ≤ 1.5 x upper limit of normal (unless bilirubin due to Gilbert's)
- •No active CNS disease
- •No detectable bone marrow involvement by lymphoma on histopathologic bone marrow examination
- •Bone marrow cellularity ≥ 15% on histopathologic bone marrow examination
- •Availability of adequate stored autologous stem cell product (≥ 2 x 106 CD34+ cells/kg)
排除标准
- •Active infection
- •Pregnant woman are excluded from the study
- •Subjects not using contraceptives are excluded from the study
- •ANC ≤ 1,500/μL and/or platelet count ≤ 100,000/μL
- •Life expectancy of ≤ 2 months
- •Prior anti-B-cell radioimmunotherapy (e.g., Zevalin or Bexxar) [Patients who have received prior anti-B-cell monoclonal antibody therapy (e.g., rituximab or epratuzumab) will NOT be excluded.]
- •Prior total body radiation therapy
- •Positive human anti-mouse antibody (HAMA) testing
结局指标
主要结局
dose-limiting toxicity
时间窗: Week 7 after Bexxar
maximum tolerated dose
时间窗: Week 7 after Bexxar
次要结局
- overall response rate(Week 13 after Bexxar)
- progression-free survival(5 years after Bexxar)
- time to treatment failure(5 years after Bexxar)