Tolerance by Engaging Antigen During Cellular Homeostasis

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".

Conditions

• Kidney Transplantation
• Renal Transplantation
• Renal Transplant Recipient

Interventions

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.

Sponsors & Collaborators

• Immune Tolerance Network (ITN)

  collaborator NETWORK

• PPD Development, LP

  collaborator INDUSTRY

• Rho Federal Systems Division, Inc.

  collaborator INDUSTRY

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Principal Investigators

• Allan D. Kirk, M.D., Ph.D. · Duke University Medical Center: Transplantation

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

19 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-07-30

Primary Completion

2023-09-06

Completion

2025-09-16

FDA Drug

Yes

Countries

• United States

Study Locations