Liver Transplantation
Conditions
Keywords
Liver transplantation, Allogeneic liver transplantation, Solid organ transplantation
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.
Interventions
DRUGMultiStem
Sponsors
University Hospital Regensburg
Healios K.K.
Prof. Dr. Marc-H. Dahlke, Ph. D.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Infusional and Acute Toxicity, Using Toxicity Scoring Mechanism | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Biopsy-proven Acute Rejection | up to day 90 (+/-30) | 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 | up to day 365 (+/-30) | 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 | up to six years | The results of routine examinations, which are necessary for all transplant patients, will be used once a year and analyzed retrospectively. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MultiStem - Cohort 1 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) | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | MultiStem - Cohort 1 |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Region of Enrollment Germany | 3 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 3 / 3 |
Outcome results
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.
Time frame: up to day 30 (+10)
Population: A Per-protocol (PP) population consisting of all patients of the ITT population who showed no major protocol violations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MultiStem - Cohort 1 | Infusional and Acute Toxicity, Using Toxicity Scoring Mechanism | 0 Participants |
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.
Time frame: up to six years
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).
Time frame: up to day 365 (+/-30)
Population: A Per-protocol (PP) population consisting of all patients of the ITT population who showed no major protocol violations. Protocol violations that may have an impact on the study outcome were considered as major protocol violations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MultiStem - Cohort 1 | Evidence Confirming That MultiStem Does Not Promote Malignant Transformation or Tumor Growth | 0 Participants |
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.
Time frame: up to day 90 (+/-30)