Safety and Preliminary Efficacy of Donor-derived Regulatory Dendritic Cell (DCreg) Infusion and Immunosuppression Withdrawal in Living Donor Liver Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Proportion of Safety Events
研究概览
简要总结
Phase I/II, single center, prospective, open-label, non-controlled, non-randomized, interventional, cohort study in which low risk living donor liver transplant (LDLT) recipients will receive a single infusion of donor-derived DCreg 1 week prior to transplantation. All patients will be maintained on MPA and Tacrolimus (Tac) for the 1st 6 months after transplantation. At that time point, recipients meeting specific criteria will be slowly weaned off MPA per standard of care over a period of 6 months. Participants will then be evaluated for TAC weaning at 1 yr after transplantation. Those who meet specific criteria be weaned off Tac over 6 months . Successfully weaned participants who remain rejection-free will undergo 3 years of follow-up after the last dose of immunosuppression.
详细描述
Phase I/II, single center, prospective, open-label, non-controlled, non-randomized, interventional, cohort study in which low risk living donor liver transplant (LDLT) recipients will receive a single infusion of donor-derived DCreg with concurrent mycophenolic acid (MPA) therapy (1/2 dose) 1 week prior to transplantation. All patients will be maintained on MPA and Tacrolimus (Tac) for the 1st 6 months after transplantation. At that time point, recipients meeting specific criteria (no rejection and permissive liver function tests (LFTs)) will be slowly weaned off MPA per standard of care over a period of 6 months. Participants will then be evaluated for TAC weaning at 1 yr after transplantation. Those who meet the criteria of no rejection and permissive LFTs will undergo a protocol liver biopsy and proceed to Tac weaning over 6 months if liver biopsy is permissive. Successfully weaned participants who remain rejection-free will undergo 3 years of follow-up after the last dose of immunosuppression. They will undergo a liver biopsy at 1 yr and 3 yrs after immunosuppression withdrawal. Participants who are removed from the study protocol at any time will return to standard of care but will continue to be followed by the study team and may undergo a liver biopsy at the end of the study (4.5 yrs after transplantation). For subjects who return to standard of care (on immunosuppression at end of study), the year 4.5 biopsy will be optional.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- •Able to understand and provide informed consent;
- •Male or female between the ages of 18-55;
- •Meet all standard institutional and UNOS criteria for liver donation;
- •For females of childbearing potential, a negative urine or serum pregnancy test;
- •Negative for HIV (5th generation Test and NAT), HTLV-1, HTLV-2;(*)
- •Negative for hepatitis C (antibody and NAT), hepatitis B (surface antigen and NAT)(*)
- •Low risk recipient approved for LDLT, irrespective of gender, race, or ethnic background. Low risk is defined by absence of exclusion criteria (below).
- •Between ages 18 and 75 years
- •Undergoing de novo (first) liver transplant
- •Female subjects of childbearing potential must have a negative pregnancy test upon study entry.
- •Agreement to use contraception; according to the FDA Office of Women's Health (http://www.fda.gov/birthcontrol), there are a number of birth control methods that are more than 80% effective. Female participants of child-bearing potential must consult with their physician and determine the most suitable method(s) from this list to be used from the time that study treatment begins until 1 year after completion of immunosuppression withdrawal.
- •(*)does not preclude donors from undergoing leukapheresis but cells may not be infused into recipient.
排除标准
- 未提供
研究组 & 干预措施
Study arm
Living donor liver transplant recipients receiving donor-derived DCreg infusion. This is a single arm study
干预措施: Regulatory Donor-Derived Dendritic Cell infusion (Biological)
结局指标
主要结局
Proportion of Safety Events
时间窗: 6 years
1\. Safety: Safety will be determined by assessing the percentage of subjects experiencing the following events: i) CTCAE Grade 4 or higher infusion reaction; ii) CTCAE Grade 4 or higher infection; iii) Malignancy other than non-melanoma skin cancer or HCC recurrence; iv) Rejection resulting in recipient death or retransplantation; v) Biopsy-proven severe acute rejection; vi) Any grade chronic rejection; vii) Non-surgical graft loss; viii) Recipient death;
Preliminary Efficacy
时间窗: 2.5 years
Proportion of patients able to achieve staged immunosuppression withdrawal with operational tolerance
次要结局
- Donor Specific Antigen (DSA) Levels(6 years)
- Change in Renal Function(from baseline to 4.5 years post transplantation)
- Change in Quality of Life(1 year post-transplantation (prior to weaning) 4.5 years post transplantation)
- Change in Cardiovascular Risk Factors (Systolic Blood Pressure)(from baseline to 4.5 years post transplantation)
- Change in Cardiovascular Risk Factors (Triglycerides)(from baseline to 4.5 years)
研究者
Angus W. Thomson PhD DSc
Distinguished Professor of Surgery and Immunology
University of Pittsburgh