Phase II Study of Reduced-Intensity Allogeneic Stem Cell Transplant for High-Risk Chronic Lymphocytic Leukemia (CLL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 68
- 试验地点
- 25
- 主要终点
- 2-year Progression-free Survival in Early Disease Participants
研究概览
简要总结
RATIONALE: Giving low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as rituximab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus, sirolimus, and methotrexate after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well donor stem cell transplant works in treating patients with high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma.
详细描述
OBJECTIVES:
Primary
- To determine if this treatment can improve 2-year current progression-free survival (PFS) in the early disease cohort compared to historical controls. Specifically, we plan to study whether we can achieve 2-year PFS ≥ 70% and to exclude 2 year PFS ≤ 50%
Secondary
- To determine whether in the advanced disease cohort we can achieve 2-year current PFS ≥ 50% and to exclude 2-year PFS ≤ 30%
- To assess objective response rate.
- To assess the incidence of grade 2-4 and 3-4 acute graft-vs-host disease (GVHD).
- To assess the incidence of extensive chronic GVHD.
- To assess the incidence of treatment-related mortality at 100 days and 1 year
- To assess overall survival
- To assess donor chimerism for CD3+ cells at 1 and 2 years after transplantation
- To investigate the presence of donor antigen-specific T-cell clones before and after withdrawal of immune suppression.
- To compare the relapse profiles of patients with T-cell responses against CLL to those whose CLL cells are not reactive
- To prospectively examine the impact of high-risk genomic features and immune-based single nucleotide polymorphisms on response, toxicity, and 2-year PFS to reduced intensity allogeneic stem cell transplant
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
- 18 Years 至 69 Years（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
研究组 & 干预措施
Treatment (Combination of chemotherapy and transplant)
See detailed description
干预措施: rituximab (Biological)
Treatment (Combination of chemotherapy and transplant)
See detailed description
干预措施: busulfan (Drug)
Treatment (Combination of chemotherapy and transplant)
See detailed description
干预措施: cyclophosphamide (Drug)
Treatment (Combination of chemotherapy and transplant)
See detailed description
干预措施: fludarabine phosphate (Drug)
Treatment (Combination of chemotherapy and transplant)
See detailed description
干预措施: methotrexate (Drug)
Treatment (Combination of chemotherapy and transplant)
See detailed description
干预措施: sirolimus (Drug)
Treatment (Combination of chemotherapy and transplant)
See detailed description
干预措施: tacrolimus (Drug)
Treatment (Combination of chemotherapy and transplant)
See detailed description
干预措施: allogeneic stem cell transplant (Procedure)
结局指标
主要结局
2-year Progression-free Survival in Early Disease Participants
时间窗: 2 years post-registration
Percentage of participants who were alive and progression free at 2 years for participants with early disease stage. The 2 year progression free survival, with 95% confidence interval, was estimated using the Kaplan Meier method. A progression is defined as one of the following events: * \>= 50% increase in the products of at least two lymph nodes on two consecutive determinations two weeks apart (at least one lymph node must be \>= 2 cm); appearance of new palpable lymph nodes. * \>= 50% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin; appearance of palpable hepatomegaly or splenomegaly, which was not previously present. * \> 50% increase in peripheral blood lymphocytes with an absolute increase \> 5000/μL. * Transformation to a more aggressive histology (i.e., Richter's syndrome or prolymphocytic leukemia with \>= 56% prolymphocytes).
次要结局
- Treatment-related Mortality(6 months post-transplant)
- Acute Graft-vs-host Disease (GVHD)(5 years post-registration)
- Response(5 years post-registration)
- Overall Survival(5 years post-registration)
- Chronic GVHD(5 years post-registration)
- Chimerism for CD3(5 years post-registration)