Safety and Tolerance of Immunomodulating Therapy With Donor-specific MSC in Pediatric Living-Donor Liver Transplantation

NCT02957552 | Unknown Phase 1 DMC

• 2 other identifiers: MYSTEP12014-003561-15
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Since the introduction of calcineurin-based immunosuppression, patient and graft survival in pediatric liver transplantation (LT) improved significantly. However, in contrast, calcineurin inhibitor (CNI) toxicity leads to significant morbidity and impairs quality of life for recipients. Moreover, CNI cannot prevent long-term allograft inflammation and fibrosis. Mesenchymal stem (stromal) cells (MSC) have potent immunomodulatory properties potentially promoting allograft tolerance and ameliorating toxicity of exposure to high dose CNI. Previous trials for non-solid organ transplant indications have shown an excellent safety profile of intravenous MSC application. The MYSTEP1 trial aims to investigate safety and benefits portal and intravenous MSC infusion in pediatric LT.

Conditions

Pediatric Liver Transplantation

Outcome Measures

Primary Outcomes (3)

• Number of participants with MYSTEP-score grade 3 and grade 2 (toxicity of MSC infusion)

  In order to evaluate and quantifiy acute clinical complications related to MSC infusion, the investigators defined the MYSTEP score, a specific pediatric infusional toxicity scoring system (adapted from MiSOT-I score). The score focusses on description of intraportal, pulmonary and systemic toxicity. For each of these three modalities, degrees of severity between 0 (no treatment emergent adverse event) and 3 (severe treatment emergent adverse event) have been defined.

  28 days

• Number of participants with occurrence of any severe adverse events (SAE)

  A particular focus will be on viral infections and reactivation (ADV, HCMV, EBV, Hepatitis B, Hepatitis C and Hepatitis E), bacterial or fungal infections.

  Two years

• Graft function after liver transplantation - Number of participants with abnormal liver tests

  Graft function after liver transplantation, measured by aminotransferase and gamma glutamyl transferase activity, bilirubin, albumin and INR.

  Two years

Secondary Outcomes (4)

• Individual need for immunosuppressive medication

  Two years

• Time to first biopsy-proven acute rejection (BPAR)

  Two years

• Immune monitoring: donor-specific antibodies (DSA)

  Two years

• Patient and graft survival at 1 and 2 years after liver transplantation

  up to Two years

Study Arms (1)

Treatment with Mesenchymal Stem Cells

EXPERIMENTAL

Two doses of 1 x 10\^6 MSCs/kg body weight: * first administration intraoperatively via intraportal infusion * second infusion via intravenous infusion on postoperative day 2 (+/- 1 day) Standard immunosuppressive treatment consisting of steroids, basiliximab and tacrolimus according to the center's pediatric liver transplantation protocol

Biological: Mesenchymal Stem Cells

Interventions

Mesenchymal Stem Cells BIOLOGICAL

Donor-specific, bone marrow derived mesenchymal stem (stromal) cells

Treatment with Mesenchymal Stem Cells

Eligibility Criteria

• Age: 8 Weeks - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Written informed consent (patients, both parents and / or legal guardian)
• age ≥ 8 weeks and ≤ 18 years
• undergoing living donor liver transplantation for chronic terminal liver failure
• Body weight \> 5kg

You may not qualify if:

• No suitability of the living-donor
• Pregnant or breastfeeding
• If appropriate: no use of adequate contraception
• Acute liver failure; highly urgent transplantations
• Receiving any form of solid organ retransplantation
• Multi-Organ-Transplantations
• Active autoimmune disease
• Pre-existing renal failure with eGFR \< 50 ml/min/1.73 m2 or requiring hemodialysis
• Reduced pulmonary function (lung function test in children older than 6 years: FEV1 and FVC \< 70% of age-appropriate norm) or clinical suspicion of pulmonary disease affecting patient's physical performance, requiring invasive or non-invasive mechanical ventilation.
• History of pulmonary embolism
• Pulmonary hypertension and / or right ventricular load in echocardiography
• Cardiac function: left ventricular shortening fraction (FS) \< 25%
• Clinically significant systemic infections
• Critical care treatment like mechanical ventilation, dialysis or vasopressor agents.
• HIV seropositive, HTLV seropositive, Hepatitis B/C seropositive

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University Children's Hospital

Tübingen, 72076, Germany

RECRUITING

Study Officials

• Ekkehard Sturm, MD, PhD

  University Hospital Tuebingen, Germany; Dept. for Pediatric Gastroenterology and Hepatology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Steffen Hartleif, MD

CONTACT

+49-7071-29-0; steffen.hartleif@med.uni-tuebingen.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Pediatric Gastroenterology and Hepatology

Study Record Dates

• First Submitted: November 2, 2016
• First Posted: November 7, 2016
• Study Start: March 10, 2017
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2021
• Last Updated: November 14, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)