Clinical trial NCT05456243: Adipose-derived MSC to Treat Rejection in Kidney Transplant Recipients
Official title: Safety of Intraarterial Infusion of Adipose Tissue-derived Mesenchymal Stromal Cells to Treat Antibody-mediated and Cellular Rejection in Adult Kidney Transplant Recipients (AMSCAR)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Kidney Transplant
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2022-07-13
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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
  * Peripheral Arterial Disease (PAD), patients who have had prior vascular interventions for PAD in the index lower extremity.
* Acute illness within 30 days of screening.
* History of allergy or intolerance to iodinated contrast agents
* Women of childbearing potential or male subjects with female partners of childbearing potential unwilling to use an effective method of contraception during and for 12 months post-treatment.
* History of or current evidence of alcohol abuse, illicit drug use or dependence
* Active COVID 19 or positive test for the SARS-CoV-2 virus
* History of malignancy within 5 years of enrollment. History of adequately treated in-situ cervical carcinoma and/or adequately treated skin cancer (basal or squamous cell) will be permitted
* Serologic evidence of human immunodeficiency virus 1 or 2 infection
* Epstein Barr Virus (EBV) sero-negativity (EBV naïve)
* Cytomegalovirus (CMV) sero-negativity
* Active post-transplant opportunistic infections at the time of screening (CMV, BK virus, polyoma virus, EBV)
* Active Hepatitis B or Hepatitis C infection (e.g. NAT positive), and/or HBV core antibody positivity. Subjects with previously treated Hepatitis C (NAT negative, HCV IgG positive), or those with HBV surface antibody positive but HBV core antibody negative subjects will not be excluded from the study.
* Have received a kidney transplant from a Hepatitis C positive donor and plan to receive anti-viral treatment after transplant
* Any chronic condition for which anti-coagulation cannot be safely interrupted for kidney biopsy based on the CHA2DS2-VASc score of ≥ 6 risk stratum. If subjects fall into either the high or the moderate thrombotic risk, they will be deemed to be not safe to interrupt anticoagulation:

  * High thrombotic risk: Mechanical heart valve: Any mitral valve prosthesis, any caged-ball or tilting disc aortic valve prosthesis, recent (within 6 months) stroke or transient ischemic attack; Atrial Fibrillation: CHADS2 score 5-6, CHA2DS2-VASc score 7-9, recent (within 3 months) stroke or transient ischemic attack, rheumatic valvular heart disease; Venous thromboembolism: Recent (within 3 months) VTE, severe thrombophilia (e.g. deficiency of protein C, protein S, or antithrombin; antiphospholipid antibodies; multiple abnormalities)
  * Moderate thrombotic risk: Mechanical heart valve: Bileaflet aortic valve prosthesis and 1 or more of the of following risk factors: atrial fibrillation, prior stroke or transient ischemic attack, hypertension, diabetes, congestive heart failure; Atrial Fibrillation: CHADS2 score 3-4, CHA2DS2-VASc score 4-6; Venous thromboembolism: VTE within the past 3 to 12 months, non-severe thrombophilia (e.g. heterozygous factor V Leiden or prothrombin gene mutation), recurrent VTE
  * For all other subjects, anticoagulation can be safely interrupted for 3 days prior to infusion and resumed a day after the infusion.
* Positive pregnancy test
* Participation in any other studies that involved investigational drugs or regimens in the preceding year
* Any other condition, in the investigator's judgment, that increases the risk of A-MSC infusion or prevents safe trial participation
* Unwilling or unable to adhere to study requirements and procedures
* Per Banff criteria category 6: the presence of other changes not considered to be caused by acute or chronic rejection, BK-Virus Nephropathy, Posttransplant Lymphoproliferative Disorder, Calcineurin Inhibitor Toxicity, Acute Tubular Injury, Recurrent Disease, De Novo Glomerulopathy (Other Than TG), Pyelonephritis or Drug-Induced Interstitial Nephritis

Primary outcomes:
measure: Worsening kidney allograft rejection
timeFrame: 28 days after A-MSC infusion
measure: Adverse Events
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Timucin Taner, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: