Trial of Adoptive Immunotherapy With TRACT to Prevent Rejection in Living Donor Kidney Transplant Recipients

NCT02145325 | Completed Phase 1 DMC

• 1 other identifier: STU00091850
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Regulatory CD4+CD25+ T cells (Treg) derived from the thymus and/or peripheral tissues have been demonstrated to broadly control T cell reactivity (14). Importantly, Tregs have been shown to control immune responsiveness to alloantigens and significantly contribute to operational tolerance in transplantation models (15, 16). However, there have been limited efforts to harness the therapeutic potential of directly isolated CD4+CD25+ Treg cells for controlling graft rejection and inducing transplantation tolerance, such as for kidney transplants. In order for CD4+CD25+ Treg cells to be used as a clinical treatment, the following cell properties could be necessary: ex vivo generation of sufficient numbers of cells, migration in vivo to sites of antigenic reactivity, ability to suppress rejection in an alloantigen-specific manner, and survival/expansion after infusion for a critical, but currently unknown, period of time. Our published work and that of other investigators has demonstrated 1) the feasibility of expanding Treg ex vivo, 2) the ability of these cells to downregulate allogeneic immune responses in vitro, and 3) the efficacy of Treg for prevention of allograft rejection in animal models (15,16). We have developed strategies for the ex vivo expansion of naturally occurring human Tregs (nTregs) that allow for the practical employment of this cellular therapy in the clinic. Our central hypothesis is that sufficient human nTreg can be expanded ex vivo and used to both prevent renal transplant rejection and facilitate the reduction and subsequent withdrawal of drug-based immunosuppression. This study will allow for us to define the safety of Treg adoptive cellular transfer (TRACT) in living donor renal transplant recipients that draws upon our extensive preclinical experience with expanded Tregs, as well as our recognized clinical expertise with designing immunosuppressive regimens compatible with this type of therapeutic cell transfer.

Conditions

End Stage Renal Disease

Keywords

Kidney transplant; Regulatory T cells; Leukopheresis; Immune cells; Stem Cells; Tolerance

Outcome Measures

Primary Outcomes (1)

• Safety Profile Assessment of TRACT

  The primary safety endpoint is the evaluation of cellular related toxicities immediately and within 24 hrs post infusion of TRACT. Since TRACT is being administered to promote immunosuppression and prevent rejection, specific adverse events (subsequent rejection episodes, allosensitization, development of opportunistic infection) within 30 days of infusion will be monitored.

  5 years (60 weeks)

Study Arms (1)

Expanded Tregs

EXPERIMENTAL

Immune cells in the blood will be removed by leukopheresis procedure and stored for later manufacture of subject's Expanded Tregs cellular product. Two months following subject's kidney transplantation, subject will be given an Expanded Tregs infusion intravenously in the Northwestern Clinical Research Unit.

Drug: Expanded Tregs

Interventions

Expanded Tregs DRUG

Expanded Tregs

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who are males or females age 18-65 years.
• Donor Age 18-65 years.
• No prior organ transplant
• Patients who are single-organ recipients (kidney only).
• Women who are of childbearing potential must have a negative serum pregnancy test before transplantation and agree to use a medically acceptable method of contraception throughout the treatment period.
• Subject (recipient) is able to understand the consent form and give written informed consent.

You may not qualify if:

• Known sensitivity or contraindication to sirolimus, tacrolimus or MMF.
• Patient with significant or active infection.
• Patients with a positive flow cytometric crossmatch using donor lymphocytes and recipient serum.
• Patients with PRA \>20%
• Patients with current or historic donor specific antibodies
• Body Mass Index (BMI) of \< 18 or \> 35
• Patients who are pregnant or nursing mothers.
• Patients whose life expectancy is severely limited by diseases other than renal disease.
• Ongoing active substance abuse, drug or alcohol.
• Major ongoing psychiatric illness or recent history of noncompliance.
• Significant cardiovascular disease (e.g.):
• Significant non-correctable coronary artery disease;
• Ejection fraction below 30%;
• History of recent myocardial infarction.
• Malignancy within 3 years, excluding nonmelanoma skin cancers.

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University Comprehensive Transplant Center

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Kidney Failure, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Anton Skaro, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 20, 2014
• First Posted: May 22, 2014
• Study Start: April 1, 2014
• Primary Completion: June 16, 2016
• Study Completion: June 16, 2016
• Last Updated: October 8, 2019

Record last verified: 2019-10

Locations

US (1)