NCT02176434招募中不适用
Pilot Feasibility Study of Combined Kidney and Hematopoietic Stem Cell Transplantation to Cure End-stage Renal Disease
适应症
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Renal allograft acceptance and ability to discontinue immunosuppressive therapy at 1 year
研究概览
简要总结
This pilot study of combined kidney and hematopoietic stem cell transplantation attempts to establish a protocol to induce immunological tolerance as a new strategy to prevent renal graft rejection. If successful, this strategy would restore renal function, while avoiding the risks associated with long-term standard anti-rejection therapy, and would represent the first option to cure end-stage renal disease.
详细描述
Trial design This is an open-label feasibility study of combined Human Leukocyte Antigen (HLA)-matched sibling hematopoietic stem cell and kidney transplantation. The study will be performed at the University Hospital of Zurich. The pilot study will include 5 to 8 donors and 5 to 8 recipients. We expect that 4 out of 5 recipients should be off immunosuppressive therapy at 6-12 months.
Study protocol
- Non-study-specific interventions before transplantation Donor and recipients will be screened according to the established internal guidelines for living donor kidney and hematopoietic stem cell transplantation of the Transplantation Center of the University Hospital Zurich.
- Study-specific interventions before transplantation
- Potential candidates will be informed about this study by the treating physician. Interested patients will be informed in details about the study protocol, the potential benefits and risks. The patient will have sufficient time to decide to participate to this study or to undergo standard transplantation, to read and sing the informed consent form.
- Total lymphoid irradiation: for the optimal planning of the total lymphoid irradiation, a mapping CT will be performed 2-4 weeks before therapy and repeated on day 1 after kidney transplantation.
- Blood draw for establishment of chimerism determination.
- The recipient will undergo one leukapheresis procedure before starting the conditioning regimen in order to bank cells for future scientific studies.
- Stem cell mobilization and isolation in the donor by leukapheresis will be performed according to the standard protocols of the Stem cell transplantation center of the University Hospital Zurich
- Donor-derived hematopoietic progenitor cells will be isolated from peripheral leukocytes by positive selection (CD34+ cells) using the Magnetic-Activated Cell Sorting (MACS) technology according to SOPs of the certified hematology laboratory of the University Children's Hospital Zurich. CD34 negative cells will be analyzed by Fluorescence-Activated Cell Sorting (FACS) to determine the amount of CD3 positive cells. Stem cells and flow through will be frozen until the transplant according to standard operating procedure (SOP) at the stem cell transplantation center at the University Hospital Zurich.
- Since irradiation might reduce fertility the possibility of sperm conservation before transplantation will be offered to male recipients.
- Induction protocol
- Kidney transplantation (day 0)
- A CT scan will be performed at day 1 after transplantation for a correct definitive plan of the irradiation protocol.
- Immunosuppression: in the first weeks after kidney transplantation the recipients will be treated with standard immunosuppression, including methylprednisolone, prednisone, mycophenolate mofetil and cyclosporine A.
- Additionally the patient will be treated with:
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients, who are eligible for kidney transplantation
- •Males or females 18 - 70 years of age.
- •Subjects must have an HLA-matched sibling donor 25-70 years of age
- •Men and women of reproductive potential must agree to use a reliable method of birth control
- •Ability to understand and provide informed consent.
排除标准
- •Evidence of uncontrolled active infection (including replicating HIV, Hepatitic B and Hepatitis C) as defined by:
- •clinical syndrome consistent with viral or bacterial infection, or
- •fever with a clinical site of infection identified, or
- •microbiologically documented infection
- •Contraindication to therapy with any one of the proposed agents (e.g. allergy to ATG).
- •Serologic positivity to HIV.
- •Women of childbearing age in whom adequate contraception cannot be maintained, pregnant women or nursing mothers.
- •Malignancy within the past two years, for which waiting time for transplantation is required by PENN registry consult, thereby excluding non-melanoma skin cancer and carcinoma in situ of the cervix.
- •Liver transaminases > 3 x normal value.
- •Cardiac ejection fraction < 50% by radionuclide ventriculography or echocardiography.
- •Forced Expiratory Volume (FEV1) < 50% predicted or corrected Diffusing Capacity for Carbon Monoxide (DLCO) < 50 % predicted.
- •Blood group incompatibility in the host-vs-graft direction.
- •High risk of primary kidney disease recurrence
结局指标
主要结局
Renal allograft acceptance and ability to discontinue immunosuppressive therapy at 1 year
时间窗: 1 year
* Renal function as determined by eGFR (CKD-EPI) and proteinuria after discontinuation of immunosuppressive therapy (1 year after transplantation) * Evidence for rejection according to Banff classification, as assessed in the transplant biopsy performed after discontinuation of immunosuppressive therapy (1 year after transplantation)
次要结局
- Quality of life (questionnaire)(6 and 12 months)
- T cell recovery and immune reconstitution(6 and 12 months)
- Absence of graft versus host disease(6 and 12 months)
- Engraftment of hematopoietic stem cells (chimerism)(6 months)
- Absence of renal allograft rejection(6 and 12 months)
- Absence of opportunistic infections (immune competence)(6 and 12 months)
研究者
研究点 (2)
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