NCT01927120已完成2 期
In Vivo Treg Expansion and Graft-Versus-Host Disease Prophylaxis With IL-2, Sirolimus, and Tacrolimus Following Allogeneic Hematopoietic Cell Transplantation
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Regulatory T Cells (Tregs)/Total CD4+ Cells at Day 30 Post-HCT
研究概览
简要总结
IL-2 add-back post allogeneic hematopoietic stem cell transplant (HSCT), combined with Sirolimus (SIR), Tacrolimus (TAC) will optimize Treg reconstitution and prevent graft versus host disease (GVHD).
详细描述
- Determine if a GVHD prophylaxis regimen of IL-2/SIR/TAC enhances in vivo Treg differentiation and growth; 2) Study the safety and effects of IL-2/SIR/TAC on the incidence of acute and chronic GVHD; 3) Evaluate the influence of dual IL-2 supplementation and mammalian target of rapamycin (mTOR) inhibition on T cell-specific signaling pathways and the polarization of emerging T helper cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have an available 8/8 human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 matched-related or unrelated donor allogeneic hematopoietic peripheral blood stem cell graft.
- •Acute myeloid leukemia, myelodysplasia, acute lymphoblastic leukemia, chronic myeloid leukemia, or myeloproliferative neoplasms requiring a matched allogeneic HSCT.
- •Acute Leukemia (AML or ALL) must be in complete remission defined as: <5% marrow blasts with no morphologic evidence of leukemia, no peripheral blasts, marrow >20% cellular, and peripheral absolute neutrophil count >1000/µL (platelet recovery is not required).
- •Myelodysplasia (MDS) and chronic myeloid leukemia (CML): Must have <5% marrow blasts.
- •Myeloproliferative neoplasms (MPN): Must have <5% peripheral / marrow blasts.
- •Adequate vital organ function:
- •Left ventricular ejection fraction (LVEF) ≥ 45% by multi gated acquisition (MUGA) scan or ECHO
- •Forced expiratory volume at one second (FEV1), forced vital capacity (FVC), and adjusted diffusing lung capacity oxygenation (DLCO) ≥ 50% of predicted values on pulmonary function tests
- •Transaminases (AST, ALT) < 2 times upper limit of normal values
- •Creatinine clearance ≥ 50 cc/min.
- •Performance status: Karnofsky Performance Status Score ≥ 80%
- •Donor eligibility: Eligible donors will include healthy sibling, relative or unrelated donors that are matched with the patient at HLA-A, B, C, and DRB1 by high resolution typing.
排除标准
- •Active infection not controlled with appropriate antimicrobial therapy
- •History of HIV, hepatitis B, or hepatitis C infection
- •Anti-thymocyte globulin, alemtuzumab, bortezomib, or cyclophosphamide administered within 14 days before or planned to receive with HCT conditioning or as part of GVHD prophylaxis in the 14 days after HCT.
- •Hypersensitivity to recombinant human IL-2
- •Chronic lymphocytic leukemia, Hodgkin lymphoma, and non-hodgkin lymphoma are excluded as these malignancies may express the IL-2 receptor and pose a potential growth signal to any present disease.
- •Sorror's co-morbidity factors with total score >4
研究组 & 干预措施
GVHD Regimen
Experimental
Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
干预措施: IL-2 (Drug)
GVHD Regimen
Experimental
Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
干预措施: Tacrolimus (Drug)
GVHD Regimen
Experimental
Graft versus host disease (GVHD) prophylaxis regimen IL-2 with Sirolimus and Tacrolimus after allogeneic hematopoietic cell transplant (HCT).
干预措施: Sirolimus (Drug)
结局指标
主要结局
Regulatory T Cells (Tregs)/Total CD4+ Cells at Day 30 Post-HCT
时间窗: 30 days post HCT
Percentage of Treg among blood CD4+ T cells at day 30 after hematopoietic cell transplantation (HCT), to compare to SIR/TAC alone data from a previous trial (median of 16%). The study was designed to capture an increase in regulatory T cells from a median of 16.0% at day +30.
次要结局
- Overall Survival at Day +365(365 days post HCT)
- Cumulative Incidence of Relapse(1 year post HCT)
- Cumulative Incidence of Grade II-IV Acute GVHD by Day +100(100 days post HCT)
- Cumulative Incidence of Chronic GVHD by Day +365(365 days post HCT)
- Incidence of Non-relapse Death(365 days post HCT)
- Incidence of Unexpected or Serious Adverse Events (AEs)(Up to days 130 post HCT)
- Proportion of Treg Among Blood CD4+ T Cells at Day +90 After HCT(90 days post HCT)
- STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 30(30 days post HCT)
- STAT3, STAT5 (Y694), and S6 Phosphorylation Among Treg and Non-Treg at Day 90(90 days post HCT)
研究者
研究点 (1)
Loading locations...
相似试验
终止
不适用
Comparison of Sirolimus Alone With Sirolimus Plus Tacrolimus in Type 1 Diabetic Recipients of Cultured Islet Cell GraftsIslet TransplantationType 1 DiabetesNCT00409461AZ-VUB
已完成
2 期
Tacrolimus and Sirolimus as Prophylaxis After Allogenic Non-myeloablative Peripheral Blood Stem Cell TransplantationGraft Versus Host DiseaseGVHDNCT00282282Dana-Farber Cancer Institute31
已完成
2 期
Sirolimus With Tacrolimus for Graft-vs-Host Disease Prophylaxis After Un-Related Stem Cell TransplantationAcute Myelogenous LeukemiaGraft Versus Host DiseaseMyelodysplastic SyndromesNon-Hodgkin's LymphomaHodgkin's DiseaseAcute Lymphoblastic LeukemiaChronic Myelogenous LeukemiaNCT00144677Dana-Farber Cancer Institute30
已完成
2 期
Sirolimus With Tacrolimus for Graft-vs-Host Disease Prophylaxis After Related Stem Cell TransplantationHematologic MalignanciesMyelogenous LeukemiaNon-Hodgkin's LymphomaHodgkin's DiseaseAcute Lymphoblastic LeukemiaMyelodysplastic SyndromeNCT00144703Dana-Farber Cancer Institute55
已完成
2 期
Tacrolimus, Sirolimus and Methotrexate as Graft Versus Host Disease Prophylaxis After Blood Stem Cell TransplantationGraft Versus Host DiseaseHematologic MalignanciesNCT00146614Dana-Farber Cancer Institute105