Safety of Intraarterial Infusion of Adipose Tissue-derived Mesenchymal Stromal Cells to Treat Antibody-mediated and Cellular Rejection in Adult Kidney Transplant Recipients (AMSCAR)
Overview
- Phase
- Phase 1
- Intervention
- Low dose adipose tissue derived mesenchymal stromal cells (A-MSC)
- Conditions
- Kidney Transplant
- Sponsor
- Mayo Clinic
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Adverse Events
- Status
- Recruiting
- Last Updated
- 6 months ago
Overview
Brief Summary
This research study is being done to learn if an experimental treatment of infusing allogeneic adipose-derived mesenchymal stromal cells (allo-A-MSC ) directly into the renal artery is safe and can help reduce inflammation in the transplanted kidney and treat rejection.
Investigators
Timucin Taner
Principal Investigator
Mayo Clinic
Eligibility Criteria
Inclusion Criteria
- •Able to understand and provide informed consent.
- •Have received a renal transplant (first or repeat), and the most recent protocol biopsy within 3 months of consent is diagnostic for ABMR or cellular rejection.
- •Clinical Inclusion Criteria:
- •Stable renal function:
- •Serum creatinine at the time of surveillance biopsy cannot be \> 15% greater than the serum creatine prior to the biopsy (must be within 3 months of the biopsy);
- •Estimated eGFR \> 30 ml/min by MDRD.
- •Histologic Criteria for Eligibility:
- •ABMR: microvascular inflammation scores for glomerulitis (g) and peritubular capillaritis (ptc) (g:1 or 2; ptc:1 or 2).
- •Cellular rejection: tubulitis (t) (t:1or 2); interstitial inflammation (i) (i:1 or 2); intimal arteritis (v) (v: 1 or 2).
- •Mixed ABMR and cellular rejection.
Exclusion Criteria
- •Nephrotic range proteinuria (≥ 3.5g/24h), detected more than once in the year preceding screening.
- •History of post-transplant intervention for obstructive uropathy
- •One or more of the following laboratory values:
- •o Hemoglobin (Hb} ≤ 8 g/dL, Potassium (K) ≥ 5.5 mEq/dL, Alanine aminotransferase (ALT) ≥ 60 U/L, Hemoglobin A1C (HbA1c) ≥ 7%, International Normalized Ratio (INR) ≥ 2.0, Platelet count \< 50 x 109/L (patients who receive a platelet transfusion to increase their platelet count will not be excluded).
- •One or more of the following parameters:
- •o Temperature ≥ 38°C (100.4°F), Respiratory rate ≥ 20/min, Oxygen saturation (SpO2) ≤ 90%, Systemic systolic blood pressure \>160mmHg or \< 100 mmHg, Pulse \< 45/min or \> 140/min
- •Patients with the following grades/classes of vascular diseases:
- •NYHA Class 3-4 CHF
- •Uncontrolled arrhythmia, defined as: atrial fibrillation with rapid ventricular response, supraventricular tachycardia, Wolff-Parkinson-White syndrome, ventricular fibrillation, or sick sinus syndrome. Subjects with rate-controlled chronic atrial fibrillation will be allowed to participate.
- •Cerebrovascular accident (CVA) within 90 days of screening
Arms & Interventions
Low Dose Group
Adult kidney transplant recipients with subclinical rejection (biopsy-proven antibody-mediated and/or cellular rejection, including borderline rejection) will be administered one low dose of allogeneic A-MSC.
Intervention: Low dose adipose tissue derived mesenchymal stromal cells (A-MSC)
High Dose Group
Adult kidney transplant recipients with subclinical rejection (biopsy-proven antibody-mediated and/or cellular rejection, including borderline rejection) will be administered one high dose of allogeneic A-MSC.
Intervention: High dose adipose tissue derived mesenchymal stromal cells (A-MSC)
Outcomes
Primary Outcomes
Adverse Events
Time Frame: 1 year
Number of Grade 3 or higher AEs attributable to the A-MSC infusion including infusion reaction/cytokine release syndrome, per the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0). Cytokine Release Syndrome (CRS) will be defined using the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cell
Worsening kidney allograft rejection
Time Frame: 28 days after A-MSC infusion
Number of subjects to have biopsy-proven worsening kidney allograft rejection