Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
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
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 5/3/23. Questions regarding updates should be directed to the study team contact.