Phase I Study of Infusion of Umbilical Cord Blood (UCB) Derived CD25+CD4+ T-Regulatory (Treg) Cells After Nonmyeloablative Cord Blood Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose
研究概览
简要总结
RATIONALE: Giving chemotherapy, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor umbilical cord blood transplant helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T-regulatory cells after the transplant may decrease this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. However, the donor immune system may also react against the recipient's tissues (graft-versus-host disease).
PURPOSE: This phase I trial is studying the side effects and best dose of donor T-regulatory cells after an umbilical cord blood transplant in treating patients with advanced hematologic cancer or other disorder.
详细描述
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) of umbilical cord blood (UCB)-derived T-regulatory (Treg) cells.
Secondary
- Estimate the proportion of patients with detectable circulating Treg cells at 0, 1, 3, 7, and 14 days after infusion.
- Estimate the risk of grades II-IV and III-IV acute graft versus host disease (GVHD) at day +100 with the infusion of Treg cells.
- Estimate the proportion of patients with sustained donor engraftment.
- Estimate the proportion of patients with double chimerism at 6 months and 1 year.
- Determine the speed and cumulative incidence of neutrophil recovery by day 42 and platelet recovery by 6 months after UCB transplantation.
- Estimate the risk of chronic GVHD at 1 year.
- Estimate the probability of disease-free survival at 100 days and 1 year.
- Estimate the risk of fungal and viral infections at 1 year
- Estimate the risk of relapse at 1 year
- Characterize the pattern of immune cell recovery over 1 year
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ages 18 to 75 years old
- •Eligible for and co-enrolled on protocol UMN-2005LS036, for treatment of any of the following advanced hematologic malignancies:
- •Acute leukemias in complete remission (high risk CR1 or subsequent CR); chronic myelogenous leukemia (except refractory blast crisis); myelodysplastic syndrome with severe pancytopenia or complex cytogenetics, large-cell lymphoma, Hodgkin's lymphoma and multiple myeloma, chronic lymphocytic leukemia/small lymphocytic lymphoma, marginal zone b-cell lymphoma, follicular lymphoma, lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia may be eligible after initial therapy.
- •Have three partially HLA matched umbilical cord blood (UCB) units (1-2 units for UCB transplantation per MT2005-02 and 1 unit for the Treg cell infusion.)
- •Adequate organ function
排除标准
- •Patients not exposed to highly immunosuppressive single agent or multi-agent chemotherapy within 3 months, or an ablative preparative regimen for autologous hematopoietic stem cell transplant (HCT) within 1 year.
- •Pregnancy or breastfeeding
- •Current active serious infection
- •Evidence of human immunodeficiency virus (HIV) or known HIV positive serology
- •Patients with acute leukemia in morphologic relapse/persistent disease defined as >5% blasts in a > or = 15% cellular bone marrow or any % blasts if blasts have unique morphologic markers (e.g., Auer rods) or associated cytogenetic markers that allows morphologic relapse to be distinguished are not eligible.
- •Chronic myelogenous leukemia in refractory blast crisis.
- •Active central nervous system malignancy.
研究组 & 干预措施
UCB post-transplant Treg Cell Infusion
Includes patients with high risk malignancy receiving allopurinol, fludarabine phosphate, cyclophosphamide, sirolimus, total body irradiation, double umbilical cord blood transplantation and Treg infusion cells after transplant. Patients will receive differing dose levels as they are entered and assigned to determine the maximum tolerated dose.
干预措施: umbilical cord blood transplantation (Biological)
UCB post-transplant Treg Cell Infusion
Includes patients with high risk malignancy receiving allopurinol, fludarabine phosphate, cyclophosphamide, sirolimus, total body irradiation, double umbilical cord blood transplantation and Treg infusion cells after transplant. Patients will receive differing dose levels as they are entered and assigned to determine the maximum tolerated dose.
干预措施: Allopurinol (Drug)
UCB post-transplant Treg Cell Infusion
Includes patients with high risk malignancy receiving allopurinol, fludarabine phosphate, cyclophosphamide, sirolimus, total body irradiation, double umbilical cord blood transplantation and Treg infusion cells after transplant. Patients will receive differing dose levels as they are entered and assigned to determine the maximum tolerated dose.
干预措施: fludarabine phosphate (Drug)
UCB post-transplant Treg Cell Infusion
Includes patients with high risk malignancy receiving allopurinol, fludarabine phosphate, cyclophosphamide, sirolimus, total body irradiation, double umbilical cord blood transplantation and Treg infusion cells after transplant. Patients will receive differing dose levels as they are entered and assigned to determine the maximum tolerated dose.
干预措施: Cyclophosphamide (Drug)
UCB post-transplant Treg Cell Infusion
Includes patients with high risk malignancy receiving allopurinol, fludarabine phosphate, cyclophosphamide, sirolimus, total body irradiation, double umbilical cord blood transplantation and Treg infusion cells after transplant. Patients will receive differing dose levels as they are entered and assigned to determine the maximum tolerated dose.
干预措施: Total body irradiation (Radiation)
UCB post-transplant Treg Cell Infusion
Includes patients with high risk malignancy receiving allopurinol, fludarabine phosphate, cyclophosphamide, sirolimus, total body irradiation, double umbilical cord blood transplantation and Treg infusion cells after transplant. Patients will receive differing dose levels as they are entered and assigned to determine the maximum tolerated dose.
干预措施: Treg infusion (Biological)
UCB post-transplant Treg Cell Infusion
Includes patients with high risk malignancy receiving allopurinol, fludarabine phosphate, cyclophosphamide, sirolimus, total body irradiation, double umbilical cord blood transplantation and Treg infusion cells after transplant. Patients will receive differing dose levels as they are entered and assigned to determine the maximum tolerated dose.
干预措施: Sirolimus (Drug)
结局指标
主要结局
Maximum tolerated dose
时间窗: 48 Hours
Nine dose levels of CD4+CD25+ Treg are scheduled with the doses being 1, 3, 10, 30, 30+30, 100, 300, 1000, and 3000 x 10\^5 Treg/kg recipient body weight. The dose escalation will proceed in cohorts of one patient until the first dose limiting toxicity (DLT) is observed.
次要结局
- Incidence of neutrophil recovery after umbilical cord blood (UCB) transplantation(Day 42)
- Number of patients with detectable Treg cells(Days 0, +1, +3, +7, and +14 after Treg cell infusion)
- Number of Patients with grade II-IV and grade III-IV acute graft versus host disease (GVHD)(Day 100)
- Number of patients with sustained donor engraftment(Day 100)
- Number of patients with double chimerism(6 Months and 1 Year)
- Number of Patients with Chronic Graft Versus Host Disease (GVHD)(1 Year)
- Number of Patients with disease-free survival(Day 100 and 1 Year)
- Number of Patients with Fungal and Viral Infections(1 Year)
- Incidence of platelet recovery after umbilical cord blood (UCB)(6 Months After Transplant)
- Number of Patients with Disease Relapse(1 Year)
- Percent of Patients with Immune Cell Recovery(1 Year)