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

NCT01841632 | Terminated Phase 1 Results DMC

• 2 other identifiers: MISOT-I2009-017795-25
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Liver Transplantation

Keywords

Liver transplantation; Allogeneic liver transplantation; Solid organ transplantation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (1)

MultiStem

EXPERIMENTAL

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

Interventions

MultiStem DRUG

MultiStem

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Prof. Dr. Marc-H. Dahlke, Ph. D.: lead
• University Hospital Regensburg: collaborator
• Healios K.K.: collaborator

Study Sites (1)

Department of Surgery, University Hospital Regensburg

Regensburg, Bavaria, 93053, Germany

Location

Related Publications (2)

• 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.

  PMID: 21798013 BACKGROUND

• 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.

  PMID: 23151227 BACKGROUND

Results Point of Contact

• Title: Prof. Dr. Marc-H. Dahlke, Ph. D.
• Organization: University Hospital Regensburg

marc.dahlke@ukr.de

+49941944

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: April 19, 2013
• First Posted: April 26, 2013
• Study Start: April 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: August 17, 2018
• Results First Posted: August 17, 2018

Record last verified: 2017-12

Locations

DE (1)