Safety and Feasibility of Multipotent Adult Progenitor Cells for Immunomodulation Therapy After Liver Transplantation: A Phase I Study of the MiSOT Study Consortium
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Infusional and Acute Toxicity, Using Toxicity Scoring Mechanism
研究概览
简要总结
MultiStem ® is a new biological product, manufactured from human stem cells obtained from adult bone marrow. Factors expressed by MultiStem cells are believed to regulate immune system function and augment tissue repair.
Standard of care pharmacological immunosuppression after liver transplantation can achieve reasonable survival of liver grafts and patients. The side effects of this treatment, however, are clinically significant and diminish the overall success of organ transplantation as a curative therapy. It is therefore the objective of this study to implement cellular immunomodulation therapy with MultiStem as an adjunct to standard pharmacological immunosuppression with the ultimate goal of significantly reducing drug-based immunosuppression.
As this is the first study with MultiStem in this subject population it has been designed as a safety and feasibility trial. However, first evidence of a potential benefit for this patient population will be explored cautiously.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients ≥18 years of age undergoing allogeneic liver transplantation
- •Absence of any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- •Written informed consent prior to any study procedures
排除标准
- •Known allergies to bovine or porcine products or any other ingredients of the product
- •Patients older than 65 years of age
- •Patients listed in a high-urgency status that would not allow proper preparation of the study interventions
- •Patients receiving a secondary liver graft (Re-Transplantation)
- •Double organ transplant recipients
- •Pre-existing renal failure that requires or has required hemodialysis within the last year
- •Pulmonary function: FEV1, FVC, DLCO ≤50% predicted
- •Cardiac function: left ventricular ejection fraction ≤50%
- •HIV seropositive, varicella virus active infection or any other clinically relevant infection
- •History of any malignancy (including lymphoproliferative disease and hepatocellular carcinoma) except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence
- •Unstable myocardium (evolving myocardial infarction), cardiogenic shock
- •Females of childbearing potential (hormonal status and gynecological consultation required)
- •Patients with portal vein thrombosis
- •Patients with a history of pulmonary embolism
研究组 & 干预措施
MultiStem
Dose escalation
Cohort 1
Drug: MultiStem, Dose 1 of MultiStem; Route and time: Two infusions; First: intra portal at liver transplantation (day 1), second: intra venous (day 3)
Cohort 2
Drug: MultiStem, Dose 2 of MultiStem; Route and time: Two infusions; First: intra portal at liver transplantation (day 1), second: intra venous (day 3)
Cohort 3
Drug: MultiStem, Dose 3 of MultiStem; Route and time: Two infusions; First: intra portal at liver transplantation (day 1), second: intra venous (day 3)
Cohort 4
Drug: MultiStem, Dose 4 of MultiStem; Route and time: Two infusions; First: intra portal at liver transplantation (day 1), second: intra venous (day 3)
干预措施: MultiStem (Drug)
结局指标
主要结局
Infusional and Acute Toxicity, Using Toxicity Scoring Mechanism
时间窗: up to day 30 (+10)
* For the description of intraportal toxicity a doppler ultrasound examination will be performed to assess various parameters that describe velocity of flow and flow pattern. * For pulmonary toxicity the assessment begins with an arterial blood gas. If this reveals pathological findings, a chest X-ray is required for clinical reasons independent of the study enrolment. In addition, clinical data describing the need for postoperative re-intubation will be recorded and the patient is assessed for the occurrence of a pulmonary embolism according to clinical guidelines. * For systemic toxicity, the occurrence of anaphylactic shock due to standard clinical guidelines is recorded.
次要结局
- Time to First Biopsy-proven Acute Rejection(up to day 90 (+/-30))
- Evidence Confirming That MultiStem Does Not Promote Malignant Transformation or Tumor Growth(up to day 365 (+/-30))
- Evaluation of Data From Routine Examinations Following Last Study Visit for Evidence of Long Term Safety From MultiStem Administration(up to six years)
研究者
Prof. Dr. Marc-H. Dahlke, Ph. D.
Sponsor-Investigator
University Hospital Regensburg