Study of Treg Therapy in Subclinical Inflammation in Kidney Transplantation (TASK)

Overview

About this study

The purpose of this study is to to determine the safety and effectivness of a single dose of autologous polyTregs or darTregs in renal transplant recipients with subclinical inflammation (SCI) in the 6 month post‐transplant allograft protocol biopsy compared to control patients treated with CNI‐based immunosuppression.

Participation eligibility

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:

  • Subject must be able to understand and provide informed consent.
  • Age ≥ 18 years of age at the time of study entry.
  • Recipients of non- Human Leukocyte Antigen (HLA) identical living or deceased donor renal transplants.
  • Protocol renal allograft biopsy at 5 months (± 8 weeks) after transplantation with Banff i1 and/or ti1 with concomitant t scores t0, t1,t2 or t3; Banff i2 and/or ti2 with concomitant t scores t0 or t1; and without v > 0, [ptc + g] ≥2, C4d >1 (by immunofluorescence, IF), or C4d > 0 (by immunohistochemistry, IHC); confirmed by central pathologist. Subjects must not be treated for pathologic criteria (e.g., steroids).
  • Estimated glomerular filtration rate (eGFR) ≥35 ml/min at the time of study entry.
  • Maintenance immunosuppression consisting of tacrolimus, MMF/MPA (≥1000 mg/720 mg daily) ± prednisone (≤ 10 mg/day)
  • Current immunizations including TdAP, hepatitis B, pneumococcal and seasonal influenza vaccines at the time of study entry, completed prior to enrollment and no less than 14 days prior to planned manufacturing collection.
  • Documented Hepatitis B (HB) serologies must be:
    • Positive HB surface antibody, negative HB core antibody and negative HB surface antigen for recipients immune to hepatitis B;
    • Negative HB surface antibody, negative HB core antibody and negative HB surface antigen for non-immune/ HBV naïve recipients provided donor had negative HB core antibody and negative HB surface antigen at the time of donation.
  • Negative TB test (PPD, interferon-gamma release assay, ELISPOT testing) within 1 year prior to enrollment. Subjects with a history of TB (positive TB test without active infection) must have completed one of the latent TB infection treatment regimens endorsed by the CDC (Division of TB Elimination, 2016). Alternative regimens for latent TB infection eradication will be adjudicated by the site's infectious disease specialist.
  • Women subjects of childbearing potential must have reviewed the Mycophenolate Mycophenolate Risk Evaluation and Mitigation Strategy (REMS) and have a negative pregnancy test upon study entry.
  • Female subjects with child-bearing potential, must agree to use FDA approved methods of birth control for the duration of the study; subjects must consult with their physician and determine the most suitable method(s) that are greater than 80% effective.(

Exclusion Criteria:

  • Inability or unwillingness of a participant to give written informed consent or comply with study protocol.
  • History of malignancy; except adequately treated basal cell carcinoma.
  • History of graft loss from acute rejection within 1 year after any previous transplant.
  • History of transplant renal artery stenosis.
  • History of cellular rejection prior to enrollment that did not respond to steroids and/or subsequent creatinine after treatment for rejection greater than 15% above baseline.
  • Known hypersensitivity to mTOR inhibitors or contraindication to everolimus (including history of wound healing complications).
  • Any chronic illness requiring uninterrupted anti-coagulation after kidney transplantation.
  • Post-transplant DSA > 5000 MFI or post-transplant treatment with IVIg for DSA. Enrolled subjects with post-transplant DSA > 2000 MFI will not be eligible for mTOR conversion.
  • Positive HIV 1 or HIV 2 serology prior to transplantation.
  • Positive HBSAg prior to transplantation.
  • Proteinuria with urine pr/cr > 1.0 g/g.
  • Any condition requiring chronic use of corticosteroids > 10mg/day at the time of study entry.
  • Subjects requiring treatment for pathologic findings on study eligibility biopsy.
  • Active infection at the time of study entry.
  • History of active TB or latent TB without adequate treatment.
  • Serum BK virus > 1,000 copies/ml by Polymerase Chain Reaction (PCR) at the time of study entry.
  • Hematocrit < 27%.
  • Absolute Neutrophil Count (ANC) < 1,000/μL.
  • Lymphocyte count < 500/μL
  • Participation in any other studies with investigational drugs or regimens in the preceding year.
  • Any condition or prior treatment which, in the opinion of the investigator, precludes study participation.
  • Unable to provide adequate biopsy specimen (paraffin embedded formalin fixed) from eligibility biopsy (3-7 months post -transplant) for quantitative analysis.
  • EBV naïve recipient of a kidney from an EBV positive donor, historically EBV naïve recipient with primary EBV infection at the time of screening (primary anti-VCA IgM, without antibody to EBNA), positive EBV PCR

  • Hepatitis C Virus AB positive subjects with negative HCV PCR are eligible if they have spontaneously cleared infection or are in sustained virologic remission for at least 12 weeks after treatment.

  • Positive SARS-COV2 testing by RT-PCR

Treg Infusion Inclusion Criteria:

  • Individuals randomized to group 2 who continue to meet all of the enrollment criteria are eligible for Treg infusion.

  • Negative SARS-COV2 RTPCR testing within 1 week of Treg infusion

Treg Infusion Exclusion Criteria:

  • Individuals randomized to group 2 who meet any of these criteria are not eligible for Treg infusion:
    • Received any vaccination within 14 days prior to blood collection for Treg manufacture;
    • Unacceptable Treg product;
    • Positive pregnancy test for women of child bearing potential.

mTOR Conversion Inclusion Criteria:

  • Individuals who meet all of these criteria are eligible for mTOR conversion:
    • Received polyTreg infusion;
    • Inflammatory load on 2 week post-infusion biopsy has decreased by ≥50% relative to the baseline biopsy, confirmed by central pathologist.

mTOR Conversion Exclusion Criteria:

  • Individuals who meet any of these criteria are not eligible for mTOR conversion:
    • Post-transplant Donor-Specific Antibodies (DSA) > 2000 mean florescence intensity (MFI).

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Mark Stegall, M.D.

Open for enrollment

Contact information:

Nong Braaten L.P.N.

Braaten.Nong@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

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Supplemental Study Information

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