Open Actively Recruiting

Retro-active Immunological Tolerance in Patients With Well-functioning Pre-existing HLA-identical Kidney Transplants

About

Brief Summary

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determine if patients with a pre-existing, well-functioning kidney transplant from a HLA-identical living donor can be withdrawn from immunosuppressive medications without compromising allograft function through hematopoietic stem cell (HPSC) infusion from the same donor.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).

Primary Purpose
Treatment
Study Type
Interventional
Phase
Phase 1

Eligibility

Gender
All
Healthy Volunteers
Yes
Minimum Age
18 Years
Maximum Age
N/A

Recipient Inclusion Criteria:

  • Males and females ages 18 years and older with a pre- existing kidney transplant from an HLA-identical 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 for a minimum of 3 months, defined as no change in creatinine exceeding 30% of baseline.
  • 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 six months of the trial.
  • No known contraindication to administration of rATG or radiation.
  • If patient is a female of reproductive potential (i.e., no documented absence of ovaries or uterus, history of tubal ligation, or post-menopausal status) patient 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.

Recipient Exclusion Criteria:

  • Donor is identical twin.
  • ABO incompatibility with donor
  • History of multi-organ transplantation
  • History of rejection with current HLA matched kidney transplant
  • Known allergy to rabbit proteins
  • History of malignancy within the past 5 years with the exception of non-melanomatous skin cancer and low risk, early-stage malignancy with ≥90% 5-year survival not receiving chemotherapy or immunotherapy.
  • History of post-transplant major complications, including de novo malignancy, active/chronic infection or rejection, with the exception of low risk, early-stage malignancy with ≥90% 5-year survival not receiving chemotherapy or immunotherapy and non-melanomatous skin cancer.
  • Worsening renal functioning over preceding 3-month interval, defined as eGFR exceeding 30% of baseline value.
  • Pregnant (confirmed by urine or serum pregnancy test) or lactating.
  • Leukopenia (with a white blood cell count < 3,000/µL) or thrombocytopenia (with a platelet count < 70,000/µL).
  • EBV, CMV and BK PCR negative at time of HPSC infusion is preferred, but if they have had a history of + CMV/BK PCR, it should be resolved by 3 months.
  • Active bacterial, fungal, mycobacterial, or viral infection (including active hepatitis B and/or C).
  • Seropositivity for HIV 1 or 2 by 4th generation serum antibody/antigen testing, or HTLV I or II by serum antibody testing.
  • Renal disease with high risk of recurrence (i.e., focal segmental glomerulosclerosis).
  • Advanced hepatic fibrosis or cirrhosis secondary to hepatitis B and/or C diagnosis.
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia; active extra-renal autoimmune disease requiring immunosuppression.
  • Active extra-renal autoimmune disease requiring immunosuppression.
  • Neuropsychiatric illness that precludes the ability to give informed consent and/or places the patient as high risk for non-compliance with the safety monitoring requirements of the study.
  • May not have received immunotherapy drugs such as immune checkpoint inhibitors (e.g. pembrolizumab, nivolumab, and ipilimumab), tumor necrosis factor inhibitors, rituximab, and interleukin-2 within 1 year of the study treatment.
  • Current or active abuse of alcohol and/or drugs within last 6 months.
  • Body Mass Index (BMI) ≥ 40.

Donor Inclusion Criteria:

  • HLA-identical sibling on high-resolution HLA typing who 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 ≥ 12 g/dL for women and 14 g/dL for men, white blood cell count ≥ 3,000/µL, and platelets ≥ 110,000/µL.
  • Serum creatinine as expected post-kidney donation and coagulation parameter studies; or, if abnormal, the changes are not considered clinically significant.

Donor Exclusion Criteria

  • Recipient is identical twin.
  • ABO incompatibility with recipient.
  • Medically unfit to tolerate peripheral blood apheresis (e.g. small body size, poor vascular access, not a suitable candidate for placement of a central catheter).
  • Pregnant (confirmed by urine or serum pregnancy test) or lactating.
  • Seropositivity for HIV 1 or 2 by 4th generation serum antibody/antigen testing, HTLV I or II by serum antibody testing, or West Nile Virus by serum IgM and PCR.
  • Active bacterial, fungal, mycobacterial or viral infection (including active hepatitis B and/or C).
  • Psychiatric, addictive, neurological, or other disorder that compromises ability to give true informed consent for participation in this study.
  • History of malignant disease within the last 5 years other than non-melanoma skin malignancies or low risk, early-stage malignancy with ≥90% 5-year survival not receiving chemotherapy or immunotherapy.
  • No current or recent use of oral anti-coagulants. (For the purpose of this study, recent is defined as less than 60 days prior to apheresis.). Note: Use of aspirin and non-steroidal anti-inflammatory drugs, for pain and inflammation management purposes, are permitted to enroll in the study, but these drugs must be stopped 14 days prior to apheresis, however subjects who are taking aspirin for its anti-platelet/anti-thrombotic effect, are excluded.

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Study Stats
Protocol No.
22-001470
Category
Urology
Location
  • UCLA Santa Monica
  • UCLA Westwood
For Providers
NCT No.
NCT05525507
For detailed technical eligibility, visit ClinicalTrials.gov.