A Single-armed, Unblinded, Non-randomized Feasibility Study of Hematopoietic Stem Cell Infusion Following a Conditioning Regimen of Total Lymphoid Irradiation (TLI) and Anti-thymocyte Globulin (ATG) in Patients With a Pre-existing, Well-functioning HLA-matched Kidney Transplant
The study seeks to determine if patients with a pre-existing, well-functioning kidney transplant from a HLA-identical living donor can be withdrawn from immunosuppressive medications without compromising allograft function through hematopoietic stem cell (HPSC) infusion from the same donor. HPSC infusion will be preceded by a conditioning regimen of total lymphoid irradiation (TLI) and rabbit anti-thymocyte globulin (rATG).
• Males and females ages 18 years and older with a pre- existing kidney transplant from an HLA-matched living donor.
• Pre-existing living kidney transplant must be within 3 months to 5 years from date of scheduled HPSC infusion.
• No history of rejection with current HLA matched kidney transplant.
• Recipient is without post-transplant major complications, including de novo malignancy, active infection or rejection.
• Stable renal function determined per investigator discretion.
• Agreement to participate in the study and ability to give informed consent.
• Meets institutional criteria for HSPC infusion.
• Resides or is willing to stay within 3 hours distance from UCLA Medical Center by ground transportation for the first three to six months of the trial at the physician's discretion.
• No known contraindication to administration of rATG or radiation.
⁃ If participant is a female of reproductive potential (i.e., no documented absence of ovaries or uterus, history of tubal ligation, or post-menopausal status) participant must be confirmed not pregnant by a serum or urine pregnancy test) and must agree to practice a reliable form of contraception including hormonal treatments, barrier methods or intrauterine device for at least 12 months post-transplant.
⁃ Karnofsky Performance Score (KPS) ≥ 70.
⁃ Adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥ 40% by MUGA (Multi Gated Acquisition) scan or echocardiogram.
⁃ Adequate liver function defined as total bilirubin ≤ 1.5 times the upper limit of normal and AST/ALT ≤ 2.0 times the upper limit of normal.
⁃ Adequate social support based on evaluation by the UCLA bone marrow and/or renal transplant team.
• HLA-matched sibling on high-resolution HLA typing who
• a. is ≥18 years of age.
• Must meet institutional criteria for HSPC transplant donation.
• Medically fit to tolerate peripheral blood apheresis, including weighing ≥110 pounds, hemoglobin ≥11, white blood cell count ≥ 3,000/µL, and platelets ≥ 100,000/µL.
• Serum creatinine as expected post-kidney donation and coagulation parameter studies; or, if abnormal, the changes are not considered clinically significant.