A Phase I, Single Center Trial of Donor Extracorporeal Photopheresis (ECP) Treated Cell Infusion (ECP-DL) Plus Post-transplant ECP for the Prevention of Rejection in Living Donor Kidney Transplant Recipients
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 24
- 主要终点
- Incidence of Adverse Events Following Escalating Doses of ECP-DL Cells
研究概览
简要总结
This is a phase 1 trial, 36 month duration for subjects with end-stage renal disease (ESRD). The objectives of the trail are1) Determine the safety of ECP-DL cell infusion in living donor renal transplant recipients. 2) Determine rates of graft rejection and compare to historical controls.
One week prior to planned LDK transplant the donor and recipient pair will be seen for ECP-DL preparation and infusion. Donors will undergo one single unstimulated peripheral blood mononuclear cell collection using the THERAKOS® CELLEX® Photopheresis System; the cell product will then undergo ECP treatment to make ECP-DL, which will then be infused into the recipient. One week later, recipients (n=12) will undergo LDK transplant using standard of care maintenance immunosuppression without antibody induction therapy. Subsequent patients will receive cell infusions in escalating cell doses. A minimum of two months will be used as an interval between ECP-DL treatment in each tier. A staggered approach for moving to the next tier will be employed waiting no less than two months to ensure absence of adverse events using the following tier dosing schema:
Tier 1: 0.5 x 10^9 ECP-DL treated cells (n=4) Tier 2: 1 x 10^9 ECP-DL treated cells (n=4) Tier 3: 2 x 10^9 ECP-DL treated cells (n=4)
Following transplant, LDK recipients will undergo ECP using the Therakos system on two consecutive days per month for 6 months (12 treatments). Peripheral IV access will be used whenever possible.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Recipient age ≥30 and less than 70 years old.
- •Donor age ≥18 and ≤ 70 years old.
- •Recipient of a first kidney transplant from a living unrelated or living related donor that is not HLA-identical to the donor.
- •Donor willing to undergo cell collection for ECP-DL cell preparation and infusion.
- •Donors will be screened and tested for HIV-1 (antigen and nucleic acid), HIV-2, hepatitis B virus (HBV, nucleic acid and surface and core antigen), hepatitis C virus (HCV, antigen and nucleic acid), Treponema pallidum (syphilis), West Nile Virus (WNV), and CJD (screening only). and tested for human T-lymphotropic virus types 1 and 2 (HTLV-1, HTLV-2) and CMV, in accordance with established UNOS guidelines for solid organ donors.
- •Donors and recipients who test negative for TB using QuantiFERON gold assay.
- •Must be willing and able to comply with protocol-required visit schedule and visit requirement.
- •Patients who are single-organ recipients (kidney only).
- •Women who are of childbearing potential must have a negative serum pregnancy test before transplantation and agree to use a medically acceptable method of contraception throughout the treatment period. Both male and female transplant recipients must agree to the use of highly effective birth control for 12 months following ECP-DL procedure. Individuals unwilling to do so will be excluded from study participation.
- •Subjects are able to understand the consent form and give written informed consent.
排除标准
- •Known sensitivity or contraindication to everolimus, tacrolimus, or psoralen.
- •Has undergone splenectomy
- •Patients with light-sensitive diseases including (but not limited to) systemic lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porhyria, xeroderma pigmentosum, and albinism
- •Patient with significant or active infection.
- •Patients with a positive flow cytometric crossmatch using donor lymphocytes and recipient serum.
- •Patients with PRA >80%
- •Patients with current or historic donor specific antibodies
- •Body Mass Index (BMI) of < 18 or > 40
- •Patients who are pregnant or nursing mothers
- •Patients whose life expectancy is severely limited by diseases other than renal disease
- •Ongoing active substance abuse, drug or alcohol
- •Major ongoing psychiatric illness or recent history of noncompliance
- •Significant cardiovascular disease
- •Malignancy within 3 years, excluding nonmelanoma skin cancers
- •Subjects with cerebrovascular vascular disease with recent (< 6 months) stroke
- •Serologic evidence of infection with HIV or HBVs Ag positive
- •Recipient is EBV serologic negative
- •Donor CMV serologic positive to recipient CMV serologic negative
- •Recipient tests positive for HCV viral load by PCR
- •Patients with a screening/baseline total white blood cell count < 4,000/mm3; platelet count < 100,000/mm3; triglyceride > 400 mg/dl; total cholesterol > 300 mg/dl
- •Investigational drug within 30 days prior to transplant surgery
- •Anti-T cell therapy within 30 days prior to transplant surgery
- •Documented severe liver disease, defined as bridging fibrosis or cirrhosis on liver biopsy
- •Poorly controlled diabetes, defined as HbA1c of > 8.0
- •PT/INR > 2.0
- •SBP < 90 or > 180mm Hg, HR > 120 or <50bpm, Temp > 99.5F on day of proposed ECP-DL procedure
- •Patients receiving concomitant enteral or topical medical therapy with potentially photosensitizing effects
- •Lack of possible peripheral IV access (two access sites)
- •Has undergone splenectomy
- •Donor tests positive for HCV viral load by PCR
- •PT/INR > 2.0; or known hyper or hypo coagulable disorders
- •Hgb < 10.0
- •platelet count < 100,000
- •SBP < 90 or > 160mm Hg, HR > 120 or <50bpm, Temp > 99.5F on day of proposed ECP-DL procedure
- •Donors who cannot tolerate extracorporeal volume during PBMC collection
研究组 & 干预措施
ECP-DL Cell Therapy Arm
Participants will receive escalating doses of ECP-DL (extracorporeal photopheresis-derived dendritic-like) cells starting on Day -7 prior to living donor kidney transplantation. The intervention aims to evaluate the safety and immunomodulatory effects of ECP-DL cell infusion in the context of renal transplantation.
干预措施: ECP-DL treated mononuclear cell infusion (Device)
结局指标
主要结局
Incidence of Adverse Events Following Escalating Doses of ECP-DL Cells
时间窗: From Day -7 (first ECP-DL infusion) through 24 months post transplant
To determine the safety profile of escalating doses of ECP-DL cells administered to patients undergoing living donor kidney transplantation.
次要结局
- Incidence of Transplant-Related Adverse Events(Baseline through 24 months post-transplant.)
- Incidence and Severity of Infections(Baseline through 24 months post-transplant)
- Changes in Peripheral Blood Lymphocyte Subpopulations(Baseline, Day 0, Day 7, Day 30, and Month 6)
- Change in Donor-Specific T Cell Response as Measured by Mixed Lymphocyte Reaction (MLR) and ELISPOT Assays(Baseline, Day 30, and Month 6)
- Quantitative Changes in Plasma and Urine Proteins Identified by Mass Spectrometry-Based Proteomic Analysis(Baseline, Day 30, and Month 6)
研究者
Joseph Leventhal
Professor
Northwestern University