Phase I-II Dose Escalation Study of CD4+CD25+ Cells in Adult Patients Undergoing HLA-Identical Sibling Donor Peripheral Blood Progenitor Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose of CD4+CD25+ cells/kg (phase I)
研究概览
简要总结
RATIONALE: A donor peripheral stem cell transplant helps stop the growth of cancer 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. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of donor T cells may helps stop the patient's immune system from rejecting the donor's stem cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of donor T cells in treating patients with high-risk hematologic cancer who are undergoing donor peripheral blood stem cell transplant.
Note: Only Phase I portion of study was performed. Due to slow accrual, study was closed before Phase II portion of study.
详细描述
OBJECTIVES:
Primary
- To determine the maximum tolerated dose (MTD) of CD4+/CD25+ cells that can be safely administered to patients undergoing HLA-identical sibling donor Peripheral Blood Progenitor Cell (PBPC) transplantation.
- To determine whether CD4+ and CD25+ cells can be safely administered to patients with high-risk hematologic malignancies undergoing HLA-identical sibling donor PBPC transplantation.
Secondary
- To determine the incidence of grade II-IV acute graft-versus-host-disease (GVHD), chronic GVHD, relapse, and survival after administration of CD4+ and CD25+ regulatory T cells in these patients.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of a high-risk hematologic malignancy, including any of the following:
- •Acute lymphocytic leukemia
- •Acute myelocytic leukemia
- •Chronic myelogenous leukemia
- •Myelodysplastic syndrome
- •Non-Hodgkin lymphoma
- •Multiple myeloma
- •Meet eligibility criteria and co-enrolled in one of the following University of Minnesota protocols:
- •MT2001-02 consisting of myeloablative prep (cyclophosphamide and total body irradiation) followed by HLA-identical sibling peripheral blood progenitor cells (PBPC) transplantation
- •MT2001-10 consisting of nonmyeloablative prep (cyclophosphamide, fludarabine and total body irradiation) followed by HLA-identical sibling PBPC transplantation
- •Voluntarily written informed consent
- •Must have an HLA-identical sibling donor available, meeting the following criteria:
- •12 to 75 years of age, >40 kg body weight and in good health
- •Matched to recipient for HLA-A, B,DRB1 identical sibling match to recipient
- •Must be able and willing to have a separate apheresis collection performed on day -21 for the purposes of this study (in addition to the apheresis required for the transplant protocol)
- •Human immunodeficiency virus nucleic acid testing (HIV-NAT) negative, Human T-lymphotropic virus 1 (HTLV-1), HTLV-2 negative, hepatitic B and C negative
排除标准
- •Not pregnant or nursing
研究组 & 干预措施
Patients Receiving CD4+/CD25+ cells
CD4+/CD25+ cells given intravenously over 15-60 minutes on Day -2 (prior to peripheral blood progenitor cell transplant)
干预措施: CD4+CD25+ regulatory T cells (Biological)
Patients Receiving CD4+/CD25+ cells
CD4+/CD25+ cells given intravenously over 15-60 minutes on Day -2 (prior to peripheral blood progenitor cell transplant)
干预措施: allogeneic hematopoietic stem cell transplantation (Procedure)
结局指标
主要结局
Maximum tolerated dose of CD4+CD25+ cells/kg (phase I)
时间窗: Day 0 (48 hours post infusion)
Incidence of grade 3-5 infusional toxicity (phase II)
时间窗: Day 0 (48 hours post infusion)
次要结局
- Disease-free survival(Day 100 and 1 Year Post Infusion)
- Incidence of chronic graft-versus-host disease (GVHD)(Month 6 Post Infusion)
- Cumulative incidence of grade II-IV acute graft-versus-host-disease (GVHD)(Day 100 Post Infusion)
- Incidence of Relapse(Month 6 Post Infusion)
- Overall Survival(Day 100 and 1 Year Post Infusion)