Delayed Infusion of Ex Vivo Anergized Peripheral Blood Mononuclear Cells Following CD34 Selected Peripheral Blood Stem Cell Transplantation From a Haploidentical Donor for Patients With Acute Leukemia and Myelodysplasia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 6
- 主要终点
- Feasibility of making and administering the adoptive T cell product
研究概览
简要总结
RATIONALE: Giving total-body irradiation and chemotherapy, such as thiotepa and fludarabine, before a donor stem cell transplant helps stop the growth of cancer or abnormal 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 methylprednisolone and antithymocyte globulin before transplant and peripheral blood cells that have been treated in the laboratory after transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated peripheral blood cell infusion after donor stem cell transplant in treating patients with hematologic cancers or other diseases.
详细描述
OBJECTIVES:
Primary
- Establish the feasibility of delayed infusion of ex vivo anergized donor peripheral blood mononuclear cells (PBMC) after CD34 (cluster designation 34)-selected megadose haploidentical hematopoietic stem cell transplantation (HSCT) in patients with hematopoietic cancers or other diseases.
- Determine the feasibility of collecting parental allogeneic stimulator cells to induce anergy to the nonshared donor-recipient haplotype in these patients.
- Determine the feasibility of collecting donor PBMC as a source of T cells for ex vivo anergization.
- Determine the number of transplanted individuals who meet the criteria for proceeding to delayed infusion of ex vivo anergized donor PBMC.
- Establish the safety of delayed infusion of ex vivo anergized donor PBMC by establishing the maximum number of donor T cells that can be infused without unacceptable graft-versus-host disease.
Secondary
- Evaluate, in vitro, the induction and specificity of alloantigen hyporesponsiveness in donor PBMC after ex vivo anergization.
- Assess, in vitro, the function of immune cells engrafted in these patients.
- Assess, in vitro, whether alloantigen hyporesponsive donor T cells are present in these patients.
- Develop, preliminarily, in vitro data on the extent of pathogen-specific immunity and its rate of recovery.
- Describe the patterns of opportunistic infections in these 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
- — 至 50 Years（Child, 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
administration of adoptive donor lymphocyte infusion
administration of donor lymphocytes made using costimulatory blockade ex vivo
干预措施: anti-thymocyte globulin (Biological)
administration of adoptive donor lymphocyte infusion
administration of donor lymphocytes made using costimulatory blockade ex vivo
干预措施: peripheral blood lymphocyte therapy (Biological)
administration of adoptive donor lymphocyte infusion
administration of donor lymphocytes made using costimulatory blockade ex vivo
干预措施: fludarabine phosphate (Drug)
administration of adoptive donor lymphocyte infusion
administration of donor lymphocytes made using costimulatory blockade ex vivo
干预措施: methylprednisolone (Drug)
administration of adoptive donor lymphocyte infusion
administration of donor lymphocytes made using costimulatory blockade ex vivo
干预措施: thiotepa (Drug)
administration of adoptive donor lymphocyte infusion
administration of donor lymphocytes made using costimulatory blockade ex vivo
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
administration of adoptive donor lymphocyte infusion
administration of donor lymphocytes made using costimulatory blockade ex vivo
干预措施: in vitro-treated peripheral blood stem cell transplantation (Procedure)
administration of adoptive donor lymphocyte infusion
administration of donor lymphocytes made using costimulatory blockade ex vivo
干预措施: total-body irradiation (Radiation)
结局指标
主要结局
Feasibility of making and administering the adoptive T cell product
时间窗: from conditioning through administration of anergized cells on day 35-42
ability to collect sufficient cells, make anergized product with good viability, without contamination and infuse per study toxicity of the conditioning regimen, the likelihood of engraftment, and the subsequent percentage of individuals who would be eligible to receive aDLI were determined.
Safety of administering the adoptive T cell product on day 35-42 post haploidentical transplant
时间窗: the period from aDLI infusion through D100
rates of graft failure with CD34 selected product, adverse and severe adverse reactions attributable to infusion of anergized donor cells, including fever, hypotension, acute graft vs host disease, organ dysfunction
Alloreactivity engendered by administering the adoptive T cell product
时间窗: from cell infusion through day 100
occurrence and severity of acute GVHD
次要结局
- Efficacy in restoring adaptive immunity(from aDLI thorough 1 year)
研究者
Eva C. Guinan, MD
Principal Investigator
Dana-Farber Cancer Institute