Effect of BM-MSCs on Chronic AMR After Kidney Transplantation

Study Overview
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Brief Summary
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This study is designed to investigate the efficacy and safety of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) on chronic antibody-mediated rejection (cAMR) after kidney transplantation. Chronic AMR is diagnosed according to Banff criteria 2013 based on renal graft biopsy and donor specific antibodies (DSA) examination. cAMR patients are assigned to MSCs group or control group. Patients in control group are prescribed to current desensitization therapy including at least one of the following treatments: plasmapheresis (PP), intravenous immunoglobulin (IVIG), rituximab or Bortezomib, depending on individual pathological and immunological features (eg. DSA type and titer) of each study subjects. Patients in MSCs group receive additional BM-MSCs therapy besides desensitization treatments as in control group. Allogeneic BM-MSCs (1*10^6/kg) are intravenously administered every two weeks for four consecutive doses. All cAMR patients are followed up for one year. Renal function, DSA level, pathological features, patient/graft survival, and severe adverse events are monitored during the follow-up period. Immunological features of patients in both groups are consecutively examined.

Official Title
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Efficacy and Safety of Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs) on Chronic Antibody-mediated Rejection (cAMR) After Kidney Transplantation: A Multi-center Perspective Study

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Other: BM-MSCs
* Other: Desensitization therapy (PP, IVIG, rituximab or Bortezomib)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: kidney transplantation cAMR diagnosis is determined based on renal graft biopsy and DSA examination Patient is willing and capable of giving written informed consent for study participation and able to participate in the study for 12 months Exclusion Criteria: Combined or multi-organ transplantation Women who are pregnant, intend to become pregnant in the next 1 years, breastfeeding, or have a positive pregnancy test on enrollment or prior to study medication administration Donors or recipients are known hepatitis C antibody-positive or polymerase chain reaction (PCR) positive for hepatitis C Donors or recipients are known hepatitis B surface antigen-positive or PCR positive for hepatitis B Donors or recipients are known human immunodeficiency virus (HIV) infection Patients with active infection Recipients with a history of substance abuse (drugs or alcohol) within the past 6 months, or psychotic disorders that are not capable with adequate study follow- up Patients with severe cardiovascular dysfunction WBC<3*10^9/L or RBC <5g/dL Highly allergic constitution or having severe history of allergies Patients with active peptic ulcer disease, chronic diarrhea, or gastrointestinal problem affect absorption Patients with a history of cancer within the last 5 years Prisoner or patients compulsorily detained (involuntarily incarcerated) for treatment or either a psychiatric or physical (e.g. infectious disease) illness Renal graft function deteriorates due to non-immunological complication, such as surgical issues or drug nephrotoxicity

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSCs group<br>cAMR patients in this group receive additional intravenous allogeneic BM-MSCs (1*10^6/kg) every two weeks for four consecutive doses, besides current desensitization therapy including at least one of the following treatments: plasmapheresis (PP), intravenous immunoglobulin (IVIG), rituximab or Bortezomib. | Other: BM-MSCs<br>* BM-MSCs are from third-party healthy donors, and have no HLA alleles similar to renal allograft donors or reacting to positive anti-HLA antibodies in recipients.<br>* Other names: allogeneic bone marrow-derived MSCs;Other: Desensitization therapy (PP, IVIG, rituximab or Bortezomib)<br>* At least one drug or treatment is applied as desensitization therapy to decrease DSA, reduce B cells or inhibit plasma cells, depending on individual condition.<br>|
| Active Comparator: Control group<br>cAMR patients in this group receive current desensitization therapy including at least one of the following treatments: plasmapheresis (PP), intravenous immunoglobulin (IVIG), rituximab or Bortezomib. | Other: Desensitization therapy (PP, IVIG, rituximab or Bortezomib)<br>* At least one drug or treatment is applied as desensitization therapy to decrease DSA, reduce B cells or inhibit plasma cells, depending on individual condition.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated glomerular filtration rate (eGFR) | eGFR at month 12 after enrollment | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient survival rate | patient survival rate at month 12 after enrollment | 12 months | 
| Graft survival rate | graft survival rate at month 12 after enrollment | 12 months | 
| Donor specific antibody (DSA) level | Change of DSA level up to 12 months after enrollment | 12 months | 
| Pathological manifestation | Change of pathological scores according to Banff 2013 criteria | 12 months | 
| Severe adverse events |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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kidney transplantation, antibody-mediated rejection, mesenchymal stem cell therapy, donor specific antibody, acute rejection