A Prospective, Open-Label, Pilot Study of Clonal Deletion on Living-Relative Donor Kidney Transplantation
试验速览
- 阶段
- 1 期
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Dosage of immunosuppressants
研究概览
简要总结
The objective of this trial is to determine if clonal deletion before kidney transplantation can effectively reduce the need for post transplant immunosuppression. The investigators will adapt a DAWN (Drugs (immunosuppressants) Added When Needed) treatment protocol to assess the effect of clonal deletion and closely monitor acute rejection, renal function, and graft survival. 15 patients eligible for the study as described below will be enrolled.
详细描述
The objective of this trial is to determine if clonal deletion can effectively reduce the need for post transplant immunosuppressive medicine. Emphasis will be placed on adverse events that are associated with clonal deletion. The investigators will assess whether DAWN (Drugs (immunosuppressants) Added When Needed) is feasible in living-relative donor kidney transplantation and the effectiveness of clonal deletion treatment on the rate of rejection, patient survival, and graft function from day 0 to 12 months after transplantation. Numbers of patients on single drug and dual therapy immunosuppression will be counted. Additionally, the investigators would assess time to immune event (rejection or antibody), the severity of acute rejection or antibody mediated rejection by Banff criteria, the incidence of delayed graft function (defined as the need for post-transplant dialysis), and the incidence of adverse events including infection, grade 3 and above non-hematologic toxicities, and grade 4 hematologic toxicities.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Uremia patient of any race that is greater than or equal to 18 years of age but less than 60 years old
- •Recipients of a kidney from a certifiable relative donor 18-60 years of age
- •Patient is willing and capable of giving written informed consent for study participation and able to participate in the study for 12 months
排除标准
- •Women who are pregnant, intend to become pregnant in the next 1 years, breastfeeding, or have a positive pregnancy test on enrollment or prior to study medication administration
- •Patient with prior solid organ transplant or cell transplant (e.g. bone marrow or islet cell).
- •Patient is deemed likely to have a second solid organ transplant or cell transplant (e.g. bone marrow or islet cell) in next 3 years
- •Patient receiving a concurrent SOT (heart, liver, pancreas) or cell transplant (islet, bone marrow, stem cell)
- •ABO incompatible donor recipient pair or CDC crossmatch positive transplant
- •Sensitized patients (most recent anti-HLA Class I or II Panel Reactive Antibodies (PRA)>0% by a CDC-assay) or patients identified a high immunological risk by the transplant physician
- •Donor with cardiac death (non-heart beating donor)
- •Recipient CMV seronegative receiving a organ from a seropositive donor (CMV seromismatch)
- •Donor OR Recipient are known hepatitis C antibody-positive or polymerase chain reaction (PCR) positive for hepatitis C
- •Donors OR Recipient are known hepatitis B surface antigen-positive or PCR positive for hepatitis B AND recipient is HBV negative
- •Patient and/or donors with known human immunodeficiency virus (HIV) infection
- •Patient at risk for tuberculosis (TB) Current clinical, radiographic, or laboratory evidence of active or latent TB as determined by local standard of care
- •History of active TB:
- •Within the last 2 years, even if treated Greater than 2 years ago, unless there is documentation of adequate treatment according to locally accepted clinical practice Patient at risk of reactivation of TB precludes administration of conventional immunosuppression (as determined by investigator and based upon appropriate evaluation)
- •Patient with any significant infection or other contraindication that would preclude transplant
- •Patient with a history of hypercoaguable state
- •Patient with a history of substance abuse (drugs or alcohol) within the past 6 months, or psychotic disorders that are not compatible with adequate study follow-up.
- •Patient with active peptic ulcer disease (PUD), chronic diarrhea, or gastrointestinal malabsorption
- •Patient with a history of cancer within the last 5 years (exception: non-melanoma skin cell cancers cured by local resection are permitted)
- •Patient with a chest radiograph (no more than 2 months prior to randomization) consistent with an acute lung parenchymal process and malignancy
- •Patient with a hypersensitivity to any study drugs
- •Patient who have used any investigational drug within 30 days prior to the Day 1 visit
- •. Patients with autoimmune disease or patient treated with immunosuppressive therapy (eg methotrexate, abatacept, etc) for indications such as autoimmune disease or patient with comorbidity to a degree that treatment with such agents is likely during the trial
- •Prisoner or patient compulsorily detained (involuntarily incarcerated) for treatment or either a psychiatric or physical (e.g. infectious disease) illness
研究组 & 干预措施
Donor specific transfusion
Subjects with uremia will undergo donor specific transfusion before transplantation
干预措施: donor specific transfusion (Procedure)
Clonal deletion
干预措施: MMF, Bortezomib (Drug)
Drugs Added When Needed
干预措施: drugs added according to the immuno condition of the recipients (Procedure)
结局指标
主要结局
Dosage of immunosuppressants
时间窗: one year
Effectiveness of clonal deletion on reducing the dosage of immunosuppressants (calcineurin inhibitor plus mycophenolate, azothioprine, or sirolimus).
次要结局
- immune event(1 year)
- DSA(1 year)
- DGF(1 years)
- Renal function(1 year)
- Survival(1 year)