Mesenchymal Stem Cell Transplantation in the Treatment of Chronic Antibody Mediated Kidney Graft Rejection (ABMR)

Autologous Mesenchymal Stem Cell Transplantation in the Treatment of Chronic Antibody Mediated Kidney Graft Rejection (ABMR)

Transplant rejection is one of the biggest limitations in renal transplant procedures, where the kidney can undergo an acute, late acute, or chronic transplant rejection. With the advancement in transplantation protocols, acute survival of renal transplants has improved, but long-term survival is still unsatisfactory, as most of the renal transplants develop chronic graft rejection. Unfortunately, there is little the investigators know when it comes to improving long-term survival of renal transplants. Mesenchymal stem cells (MSC) have been shown to have immunosuppressive and repairing properties. The purpose of this study is to find out whether MSC in combination with standard therapy of antibody mediated rejection (ABMR) are more effective in preventing organ deterioration and maintaining kidney function.

Study Overview

• Status: Terminated
• Conditions: Interventional
• Intervention / Treatment: Other: MSC transplantation

Detailed Description

Participants will be assigned to receive the full immunosuppressive therapy indicated to treat chronic ABMR (including plasmapheresis (PF) 7x, intravenous immune globulins 100 mg/kg 7x, corticosteroid) and MSC infusions (2x106cells/kg bw after PF) (Group 1) and be compared to historic controls according to "propensity score matching" (treated with immunosuppressive therapy alone (Group 2)). Patients will undergo MSC infusions at the start of the study after each PF. One year post- infusions, patients will be evaluated and undergo kidney biopsies. Blood collection will occur at regular intervals, serum creatinine and the estimated creatinine clearance will be monthly recorded. The transplanted kidney function and morphology (US Doppler) will be evaluated.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • University Medical Centre Ljubljana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Recipients of a renal allograft, male and female patients age >18
• The eGF>20 ml/min/1.73 m2,
• Renal biopsy Criteria: chronic active ABMR.
• Written informed consent, compliant with local regulations.

Exclusion Criteria:

• Recipients of multiple organs.
• Pregnant women.
• Malignant disease in last 5 years
• Active autoimmune disease
• Active infection including hepatitis B, hepatitis C, HIV, or tuberculosis
• Evidence of congestive cardiac failure and/or acute coronary syndrome in past 6 months.
• Evidence of liver disease
• Inadequate compliance to treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Historic control; historic cohort of patients with ABMR treated with standard of care therapy
EXPERIMENTAL: MSC transplantation; patients with ABMR treated with MSC transplantation	Other: MSC transplantation; MSC transplantation: patients with ABMR treated with MSC transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of MSC transplantation as assessed by adverse events according to CTCAE Version 5Estimated glomerular filtration rate (eGFR)	Adverse events according to CTCAE Version 5	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimated glomerular filtration rate (eGFR)	eGFR at up to 12 months post MSC transplantation	12 months
Graft survival rate	Graft survival rate at 12 months post MSC transplantation	12 months

Collaborators and Investigators

• Sponsor: University Medical Centre Ljubljana
• Collaborators: Slovenian Research Agency
• Investigators: Principal Investigator: Željka Večerić-Haler, MDPhD, assist.prof.Željka Večerić-Haler, MDPhD

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2019
• Primary Completion (ACTUAL): July 23, 2019
• Study Completion (ACTUAL): July 23, 2019

Study Registration Dates

• First Submitted: June 25, 2018
• First Submitted That Met QC Criteria: July 9, 2018
• First Posted (ACTUAL): July 13, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 25, 2019
• Last Update Submitted That Met QC Criteria: July 24, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: P3-0323

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 12 months

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No