Safety Study of Multipotent Progenitor Cells for Immunomodulation Therapy After Liver Transplantation

Liver Transplantation Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01841632
• Other study ID #: MISOT-I
• Secondary ID: 2009-017795-25
• Status: Terminated
• Phase: Phase 1
• Start date: April 2013
• Est. completion date: December 2016

Study information

• Verified date: December 2017
• Source: University Hospital Regensburg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Liver Transplantation

Intervention

Drug:
• MultiStem

Locations

Country	Name	City	State
Germany	Department of Surgery, University Hospital Regensburg	Regensburg	Bavaria

Sponsors (3)

Lead Sponsor	Collaborator
Prof. Dr. Marc-H. Dahlke, Ph. D.	Athersys, Inc, University Hospital Regensburg

Country where clinical trial is conducted

Germany, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Infusional and Acute Toxicity, Using Toxicity Scoring Mechanism	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.	up to day 30 (+10)
Secondary	Time to First Biopsy-proven Acute Rejection	Per protocol biopsies will be performed on days 1, 4, 10. Additional biopsies will be taken whenever clinically necessary.	up to day 90 (+/-30)
Secondary	Evidence Confirming That MultiStem Does Not Promote Malignant Transformation or Tumor Growth	Four additional outpatient visits are planned to further evaluate the study patients (including screening for malignancies).	up to day 365 (+/-30)
Secondary	Evaluation of Data From Routine Examinations Following Last Study Visit for Evidence of Long Term Safety From MultiStem Administration	The results of routine examinations, which are necessary for all transplant patients, will be used once a year and analyzed retrospectively.	up to six years

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