NCT03504241

Tolerance by Engaging Antigen During Cellular Homeostasis

Donor-derived Mesenchymal Stromal Cells, Alemtuzumab, Co-stimulation Blockade and Sirolimus for Tolerance Induction in Adult Kidney Allograft Recipients (ITN062ST)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

Summary

Anti-rejection medicines, also known as immunosuppressive drugs, are prescribed to organ transplant recipients to prevent rejection of the new organ. Long-term use of these medicines places transplant recipients at higher risk of serious infections and certain types of cancer. The purpose of this study is to determine if: * it is safe to give mesenchymal stromal cells (MSCs) to kidney transplant recipients, and * the combination of the immunosuppressive (anti-rejection) study drugs plus the MSCs can allow a kidney transplant recipient to slowly reduce and/or then completely stop all anti-rejection drugs, without rejection of their kidney (renal) allograft, a process called "immunosuppression withdrawal".

Detailed description

Background:The most common problem following a kidney transplant is the development of acute or chronic rejection. Rejection is the immunologic reaction in which the body refuses to accept the transplanted organ. The body's immune system will make destructive antibodies that will attempt to attack the transplanted organ. In order to prevent organ rejection, all patients receiving an allograft (a graft transplanted between genetically non-identical individuals of the same species) must take anti-rejection (immunosuppressive) therapy. These medications function by lowering the body's natural immune system. Often these medications are associated with significant side effects ranging from infections to cancer. Study: This is a single center, open label, dose-escalation clinical trial in 6 adult recipients of Human Leukocyte Antigen (HLA)- non-identical, living-donor renal allografts. All participants will receive induction therapy with alemtuzumab followed by maintenance therapy with sirolimus and belatacept. A total of 2 dosing cohorts of 2 recipients each will receive 12 infusions of donor-derived MSCs starting on Day 42 post-transplant and every 4 weeks starting on Day 56 post-transplant, with a minimum of 7 days between the first and second MSC infusions. The primary objective is to determine whether immune reconstitution after lymphocyte depletion in the setting of co-stimulatory blockade and systemic MSC-derived donor antigen can promote operational tolerance in recipients of kidney allografts. Participants will be evaluated for eligibility for sirolimus withdrawal any time between week 52 and week 104 post-transplant. Participants who successfully complete sirolimus withdrawal will remain on belatacept monotherapy for at least 24 weeks before being assessed for eligibility to discontinue belatacept. Participants who successfully complete Immunosuppression Withdrawal (ISW) will then undergo 24 weeks of high frequency follow up followed by 132 weeks of standard follow up. Study participation may continue for up to seven (7) years after kidney transplant surgery. \*\*\* IMPORTANT NOTICE: \*\*\* The National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network do not recommend the discontinuation of immunosuppressive therapy for recipients of cell, organ, or tissue transplants outside of physician-directed, controlled clinical studies. Discontinuation of prescribed immunosuppressive therapy can result in serious health consequences and should only be performed in certain rare circumstances, upon the recommendation and with the guidance of your health care provider.

Conditions

• Kidney Transplantation
• Renal Transplantation
• Renal Transplant Recipient

Interventions

Type	Name	Description
BIOLOGICAL	Donor-derived Mesenchymal Stromal Cells	These MSCs are a cellular product derived from bone marrow and propagated ex vivo using FDA-approved, clinically applicable methods. Their use in kidney transplantation has been associated with a good safety profile.
DRUG	alemtuzumab	Alemtuzumab, 30 mg, given once intravenously (IV) over three hours. The infusion of alemtuzumab shall begin within 24 hours of transplantation surgery and shall be given prior to the first dose of belatacept.
DRUG	belatacept	Belatacept will be given as an intravenous (IV) infusion of 10mg /kg over 1 hour on transplantation postoperative Day 0, Days 5 and 14, then every 2 weeks (± 2 days) for 5 additional doses.Thereafter, belatacept will be given once every 4 weeks (± 5 days) at 10 mg/kg through 24 weeks post-transplant, then at 5 mg/kg every 4-weeks until the participant is evaluated for belatacept discontinuation.
DRUG	sirolimus	Rapamune® (sirolimus) (Wyeth Pharmaceuticals Inc., Philadelphia, PA) will be started on transplantation postoperative day 1 at a dose of 2 mg/day orally and adjusted to maintain goal 24-hour trough levels of 8-10 ng/ml. Participants who experience grade 3 sirolimus toxicity will undergo dose reduction.
DRUG	mycophenolate mofetil	Per protocol, and, only permitted in cases of sirolimus intolerance.
DRUG	mycophenolate acid	Per protocol, and, only permitted in cases of sirolimus intolerance.
DRUG	prednisone	Per protocol, and, only permitted in cases of sirolimus intolerance.

Timeline

• Start date: 2018-07-30
• Primary completion: 2023-09-06
• Completion: 2025-09-16
• First posted: 2018-04-20
• Last updated: 2026-02-13

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study