Stem Cell Enriched, T Cell Depleted Haplocompatible Peripheral Blood Transplantation for Children With Myelodysplastic Disease, Leukemia, Marrow Failure Syndromes, or Severe Immunodeficiency Diseases
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Engraftment at 4 weeks post bone marrow transplantation through 100 days
研究概览
简要总结
RATIONALE: Giving chemotherapy and total body irradiation before a donor bone marrow transplant or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin and removing the T cells from the donor cells before transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects and best dose of donor T cells and antithymocyte globulin when given together with chemotherapy and total-body irradiation in treating young patients who are undergoing T-cell depleted donor stem cell transplant for myelodysplastic syndrome, leukemia, bone marrow failure syndrome, or severe immunodeficiency disease.
详细描述
OBJECTIVES:
- Determine the efficacy and toxicity of stem cell-enriched, T-cell-depleted, haplocompatible allogeneic hematopoietic stem cell transplantation in children with high-risk myelodysplastic syndromes, high-risk leukemia, severe acquired or congenital cytopenias, or primary immunodeficiency diseases.
- Determine the toxicity of a fludarabine and thiotepa-containing regimen in combination with lower doses of antithymocyte globulin in these patients.
- Determine the engraftment rate in patients treated with this regimen.
- Define T-cell reconstitution in these patients.
- Determine the toxicity and effects of administering stem cell and T-cell boosts after transplantation on hematopoiesis and immune reconstitution in these patients.
OUTLINE: This is a dose-escalation study of donor CD3+ cells and antithymocyte globulin (ATG).
- Cytoreductive regimen: Patients undergo total body irradiation twice daily on days -9 to -7. Patients also receive fludarabine IV on days -6 to -2, thiotepa IV every 12 hours on day -6, and ATG IV on days -5 to -2.
- Transplantation: Patients undergo CD34-enriched, T-cell-depleted, haplocompatible allogeneic peripheral blood stem cell or bone marrow transplantation on day 0.
- Donor T-cell infusion:Patients with no active graft-vs-host disease and evidence of engraftment but low absolute CD34+ lymphocyte count at 12 weeks post transplant may receive donor CD3+ cells at 4-week intervals.
- Donor stem cell boost: Patients with engraftment but either cytokine or transfusion dependent at 12 weeks post transplant may receive a boost of donor CD34+ cells.
Cohorts of 3-6 patients receive escalating doses of donor CD3+ cells and ATG until the optimum is determined. The optimum dose is defined as the dose at which both engraftment and T-cell recovery occur, without dose-limiting toxicity, in ≥ 5 of 6 patients.
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
- 1 Year 至 17 Years（Child）
- 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
Single arm of transplant
Receiving haplocompatible T cell depleted peripheral blood stem cell transplant
干预措施: anti-thymocyte globulin (Biological)
Single arm of transplant
Receiving haplocompatible T cell depleted peripheral blood stem cell transplant
干预措施: therapeutic allogeneic lymphocytes (Biological)
Single arm of transplant
Receiving haplocompatible T cell depleted peripheral blood stem cell transplant
干预措施: fludarabine phosphate (Drug)
Single arm of transplant
Receiving haplocompatible T cell depleted peripheral blood stem cell transplant
干预措施: thiotepa (Drug)
Single arm of transplant
Receiving haplocompatible T cell depleted peripheral blood stem cell transplant
干预措施: allogeneic bone marrow transplantation (Procedure)
Single arm of transplant
Receiving haplocompatible T cell depleted peripheral blood stem cell transplant
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
Single arm of transplant
Receiving haplocompatible T cell depleted peripheral blood stem cell transplant
干预措施: in vitro-treated peripheral blood stem cell transplantation (Procedure)
Single arm of transplant
Receiving haplocompatible T cell depleted peripheral blood stem cell transplant
干预措施: total-body irradiation (Radiation)
结局指标
主要结局
Engraftment at 4 weeks post bone marrow transplantation through 100 days
时间窗: 100 days
次要结局
- Survival assessed monthly for 6 months, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 5 years post transplantation(1 year)
- Disease-free survival and infection assessed monthly for 6 months, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 5 years post transplantation(1 year)
- Graft-versus-host disease assessed monthly for 6 months, every 3 months for 2 years, every 6 months for 1 year, and then yearly for 5 years post transplantation(2 years)
- CD4 count in blood < 100/mm³ at 12 weeks(12 weeks)
研究者
Morton Cowan
Professor
University of California, San Francisco