Los requisitos de elegibilidad de los participantes incluyen la edad, el sexo, el tipo y el estadio de la enfermedad, y los problemas de salud o tratamientos previos. Las pautas difieren de un estudio a otro e identifican quiénes pueden o no pueden participar. No hay garantía de que cada persona elegible que desee participar en un ensayo se inscribirá. Comunícate con el equipo del estudio para analizar la elegibilidad del estudio y la posible participación.
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.