Effect of BM-MSCs on Chronic AMR After Kidney Transplantation

Sun Yat-sen University

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Kidney Transplantation

Treatments: Other: Desensitization therapy (PP, IVIG, rituximab or Bortezomib); Other: BM-MSCs

Study type: Interventional

Funder types: Other

Identifiers

NCT02563340

MSC-KTx-cAMR-150926

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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60 participants in 2 patient groups

MSCs group

Experimental group

Description:

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.

Treatment:

Other: BM-MSCs

Other: Desensitization therapy (PP, IVIG, rituximab or Bortezomib)

Control group

Active Comparator group

Description:

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.

Treatment:

Other: Desensitization therapy (PP, IVIG, rituximab or Bortezomib)