Treg Adoptive Therapy for Subclinical Inflammation in Kidney Transplantation
Condition: Late Complication From Kidney Transplant
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to test the safety of the experimental therapy of a single
      infusion of Regulatory T cells (Tregs). The investigators want to find out what effects, good
      or bad, Tregs will have on the kidney transplant patients.

      There are different types of T cells. This study uses Regulatory T cells (Tregs), which are
      found in the blood and are part of the immune system that stops other immune cells from
      working. Tregs help to turn off the immune system after other immune cells have finished
      tackling outside infections, and Tregs keep the immune system in check so that the body does
      not attack itself. The researchers are hoping that, by giving an infusion of Tregs that the
      attack on the kidney can be stopped and kidney function will be stabilized. It is not known
      if the Treg experimental therapy can stop the inflammation in the kidney.

      In this study, the researchers will take some of Tregs from the patient, multiply them in the
      laboratory, and then infuse them back into the patient. The procedure used to multiply Tregs
      is an experimental process performed in the laboratory. Similar procedures done with mice
      have been shown to reverse inflammation but it is not known whether the results will be the
      same in humans. This therapy has not yet been done in humans outside of a research study.
    

Detailed description: 
      This is an open-label single dose pilot study in which 3 subjects with inflammation on their
      6-month surveillance biopsy following renal transplantation will receive a single infusion of
      a target of 320 million cells ex vivo selected and expanded autologous polyclonal Tregs.

      AAt the time of Treg infusion (day 0), the immnosuppression will remain unchanged and
      consists of tacrolimus and mycophenolate acid with or without steroids. On the follow up
      biopsy, 2 weeks after the Treg infusion, the inflammatory load will be assessed by computer
      assisted image analysis looking at thenumber of infiltrating cells per square mm as well as
      the percentage of renal cortex infiltrated with lymphocytes. If the inflammatory load has
      decreased by ≥50% and infused Tregs are observed in the allograft, everolimus will be started
      at 1.5 mg bid and the dose of tacrolimus will be decreased by 50%. After 2 weeks, tacrolimus
      will be discontinued. These patients will remain on everolimus and mycophenolic acid with or
      without prednisone through the end of the study and the follow up period. If on the 2-week
      follow-up biopsy, there is no decrease in the inflammatory load or there is a decrease <50%,
      no change will be made to the maintenance immunosuppressive regimen consisting of tacrolimus,
      mycophenolic acid with or without prednisone. immunosuppression. All prescribing physicians
      are enrolled in and will participate in the FDA Mycophenolate Risk Evaluation and Mitigation
      Strategy.

      Subjects will be enrolled at 4-6 week intervals. The first subject will receive an infusion
      and will be observed for 3 weeks prior to treatment of the remaining subjects. The study team
      (IND sponsor, protocol chair, and medical monitor) and the members of the DSMB will review
      the safety data of the first subject prior to proceeding.

      If no grade 3 or higher related adverse event is observed, subsequent subjects may be
      treated. Otherwise treatment will be suspended pending review.
    

Intervention name(s): Treg infusion
Intervention type(s): Biological
Intervention description(s): At the time of Treg infusion (day 0), maintenance immunosuppression will remain unchanged which consists of TAC, MPA and steroids. On follow-up biopsy 2 weeks after Treg infusion, the inflammatory load will be assessed by computer assisted image analysis looking at the number of infiltrating cells per square mm as well as the percentage of renal cortex infiltrated with lymphocytes. If the inflammatory load has decreased by ≥50% and infused Tregs are observed in the allograft, everolimus will be started at 1.5 mg bid and the dose of tacrolimus will be decreased by 50%. After 2 weeks, tacrolimus will be discontinued. These patients will remain on everolimus, mycophenolic acid and prednisone through the end of the study and the follow-up period. If on the 2-week follow-up biopsy, there is no decrease in the inflammatory load or there is a decrease <50%, no change will be made to the maintenance immunosuppressive regimen consisting of TAC, MPA and prednisone.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Tregs; Kidney transplantation