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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University Hospital Regensburg
Sponsor:
Collaborators:
University Hospital Regensburg
Athersys, Inc
Information provided by (Responsible Party):
Prof. Dr. Marc-H. Dahlke, Ph. D., University Hospital Regensburg
ClinicalTrials.gov Identifier:
NCT01841632
First received: April 19, 2013
Last updated: January 13, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Liver Transplantation
Drug: MultiStem
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University Hospital Regensburg:

Primary Outcome Measures:
  • Infusional and acute toxicity, using toxicity scoring mechanism [ Time Frame: up to day 30 (+10) ] [ Designated as safety issue: Yes ]
    • 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.


Secondary Outcome Measures:
  • Time to first biopsy-proven acute rejection [ Time Frame: up to day 90 (+/-30) ] [ Designated as safety issue: No ]
    Per protocol biopsies will be performed on days 1, 4, 10. Additional biopsies will be taken whenever clinically necessary.

  • Evidence confirming that MultiStem does not promote malignant transformation or tumor growth [ Time Frame: up to day 365 (+/-30) ] [ Designated as safety issue: Yes ]
    Four additional outpatient visits are planned to further evaluate the study patients (including screening for malignancies).

  • Evaluation of data from routine examinations following last study visit for evidence of long term safety from MultiStem administration [ Time Frame: up to six years ] [ Designated as safety issue: Yes ]
    The results of routine examinations, which are necessary for all transplant patients, will be used once a year and analyzed retrospectively.


Estimated Enrollment: 12
Study Start Date: April 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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)

Drug: MultiStem

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01841632

Contacts
Contact: Marc H Dahlke, Prof. Dr. 0049 941 944 0 Marc.Dahlke@ukr.de

Locations
Germany
Department of Surgery, University Hospital Regensburg Recruiting
Regensburg, Bavaria, Germany, 93053
Contact: Marc H Dahlke, Prof. Dr.    00499419440    Marc.Dahlke@ukr.de   
Principal Investigator: Marc H Dahlke, Prof. Dr.         
Sponsors and Collaborators
Prof. Dr. Marc-H. Dahlke, Ph. D.
University Hospital Regensburg
Athersys, Inc
  More Information

Additional Information:
Publications:
Responsible Party: Prof. Dr. Marc-H. Dahlke, Ph. D., Sponsor-Investigator, University Hospital Regensburg
ClinicalTrials.gov Identifier: NCT01841632     History of Changes
Other Study ID Numbers: MISOT-I, 2009-017795-25
Study First Received: April 19, 2013
Last Updated: January 13, 2014
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by University Hospital Regensburg:
Liver transplantation
Allogeneic liver transplantation
Solid organ transplantation

ClinicalTrials.gov processed this record on July 29, 2014