Clinical trial NCT01841632: Safety Study of Multipotent Progenitor Cells for Immunomodulation Therapy After Liver Transplantation
Official title: Safety and Feasibility of Multipotent Adult Progenitor Cells for Immunomodulation Therapy After Liver Transplantation: A Phase I Study of the MiSOT Study Consortium
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Liver Transplantation
Keywords: Liver transplantation
Allogeneic liver transplantation
Solid organ transplantation
Lead sponsor: University Hospital Regensburg
Sponsor class: OTHER
Collaborators: name: University Hospital Regensburg
name: Healios K.K.
First posted: 2013-04-26
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Infusional and Acute Toxicity, Using Toxicity Scoring Mechanism
timeFrame: up to day 30 (+10)
Secondary outcomes:
measure: Time to First Biopsy-proven Acute Rejection
timeFrame: up to day 90 (+/-30)
measure: Evidence Confirming That MultiStem Does Not Promote Malignant Transformation or Tumor Growth
timeFrame: up to day 365 (+/-30)
measure: Evaluation of Data From Routine Examinations Following Last Study Visit for Evidence of Long Term Safety From MultiStem Administration
timeFrame: up to six years
Other outcomes:
Locations:
city: Regensburg
country: Germany
facility: Department of Surgery, University Hospital Regensburg
state: Bavaria
Study officials:
References:
citation: Popp FC, Fillenberg B, Eggenhofer E, Renner P, Dillmann J, Benseler V, Schnitzbauer AA, Hutchinson J, Deans R, Ladenheim D, Graveen CA, Zeman F, Koller M, Hoogduijn MJ, Geissler EK, Schlitt HJ, Dahlke MH. Safety and feasibility of third-party multipotent adult progenitor cells for immunomodulation therapy after liver transplantation--a phase I study (MISOT-I). J Transl Med. 2011 Jul 28;9:124. doi: 10.1186/1479-5876-9-124.
citation: Dillmann J, Popp FC, Fillenberg B, Zeman F, Eggenhofer E, Farkas S, Scherer MN, Koller M, Geissler EK, Deans R, Ladenheim D, Loss M, Schlitt HJ, Dahlke MH. Treatment-emergent adverse events after infusion of adherent stem cells: the MiSOT-I score for solid organ transplantation. Trials. 2012 Nov 15;13:211. doi: 10.1186/1745-6215-13-211.