CLINICAL TRIALS IN ORGAN TRANSPLANTATION CTOT-21: Treg Adoptive Therapy in Subclinical Inflammation in Kidney Transplantation

Primary Objective

Primary Safety Objective: This study will evaluate the safety of polyTregs in adult kidney transplant recipients. Secondary Safety Objective: Participants receiving polyTregs will be evaluated for the safety of converting from CNI‐based maintenance therapy to mTOR inhibitors after Treg therapy. Primary Efficacy Objective: This study will evaluate whether polyclonally expanded Tregs (polyTregs) reduce graft inflammation relative to their enrollment biopsy compared to those receiving CNI‐based maintenance therapy with similar baseline biopsy findings. Secondary Efficacy Objective: This study will evaluate whether polyTregs can reduce graft inflammation by 25% or more in the 2 weeks after polyTreg infusion relative to the enrollment biopsy.

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This is an open label trial to determine the safety and efficacy of a single dose of autologous polyTregs in renal transplant recipients with SCI in the 3 to 7 months pos-transplant allograft biopsy compared to control patients treated with CNI-based immunosuppression. The efficacy of the Treg therapy will be assessed by the reduction of graft inflammation on biopsies performed at 7 months after study group allocation compared to the eligibility biopsy.




Inclusion Criteria: 1. Age at least 18 years of age at the time of study entry 2. Recipients of non-HLA identical living or deceased donor renal transplants 3. 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] greater than or equal to 2, C4d >1 (by IF), or C4d > 0 (by IHC); confirmed by central pathologist. Subjects must not be treated for pathologic criteria (e.g. steroids). 4. eGFR > or equal to 35 ml/min at the time of study entry 5. Maintenance immunosuppression consisting of tacrolimus, MMF/MPA ? prednisone (< than or equal to 10 mg/day) 6. Positive EBV serology 7. Current immunizations including TdAP, 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. 8. Hepatitis B serologies must be the following: a. Positive HB surface antibody, negative HB core antibody and negative HB surface antigen for recipients immune to hepatitis B b. Negative HB surface antibody, negative HB core antibody and negative HB surface antigen for nonimmune/HBV naive recipients provided donor had negative HB core antibody and negative HB surface antigen at the time of donation 9. Negative TB test within 1 year prior to enrollment. 10. Women of childbearing potential must have reviewed Mycophenolate REMS and have a negative pregnancy test upon study entry 11. Female subjects of child bearing potential, must agree to use FDA approved methods of birth control for the duration of the study Exclusion Criteria 1. History of malignancy; except adequately treated basal cell carcinoma 2. History of graft loss from acute rejection within 1 year after any previous transplant 3. History of transplant renal artery stenosis 4. 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 5. Known hypersensitivity to mTOR inhibitors or contraindication to everolimus (including history of wound healing complications) 6. Any chronic illness requiring uninterrupted anti‐coagulation after kidney transplantation 7. 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. 8. Positive HIV 1 or HIV 2 serology prior to transplantation 9. Known positive HCV Ab, HBSAg, or HBcAB serology 10. Proteinuria with urine pr/cr > 0.5 g/g 11. Any condition requiring chronic use of corticosteroids >10mg/day at the time of study entry 12. Subjects requiring treatment for pathologic findings on study eligibility biopsy 13. Active infection at the time of study entry 14. History of active TB or latent TB without adequate treatment 15. Serum BK virus >1,000 copies/ml by PCR at the time of study entry 16. Hematocrit <27%; WBC < 3,000; ANC < 1,500; lymphocytes <800; platelets <100,000 at the time of study entry 17. Participation in any other studies with investigational drugs or regimens in the preceding year 18. Any condition or prior treatment which, in the opinion of the investigator, precludes study participation 19. Unable to provide adequate biopsy specimen (paraffin embedded formalin fixed) from eligibility biopsy (3-7 months post-transplant) for quantitative analysis.

Type of Study



Outpatient CTRC
University of Colorado Hospital

Principal Investigator
Photograph of Sixto Giusti Torres,  MD

Sixto Giusti Torres, MD

Study ID

Protocol Number: 18-2679

More information available at NCT02711826

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