Tolerance by Engaging Antigen During Cellular Homeostasis

• Status: Recruiting
• Trial end date: 2027-04-01
• Target enrollment: 0
• Participant gender: All

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".

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Immune Tolerance Network (ITN); PPD; Rho Federal Systems Division, Inc.
• Treatments: Abatacept; Alemtuzumab; Everolimus; Mycophenolic Acid; Prednisone; Sirolimus

Criteria

Inclusion Criteria:

Recipient:

• Adult candidates of an human leukocyte antigen (HLA)-non-identical, living-donor kidney transplant:

--Candidates must meet the United Network for Organ Sharing (UNOS) criteria, including laboratory criteria, for transplant listing;

• Evidence of established immunity to Epstein-Barr Virus (EBV) as demonstrated by serologic testing;

• Serological evidence of prior Cytomegalovirus (CMV) infection if donor is CMV positive;

• For women of child bearing potential:

• A negative serum or urine pregnancy test with sensitivity of less than 50 mIU/mL within 72 hours of start of study medication; and

• Agreement to use contraception:

--- According to the FDA Office of Women's Health (http://www.fda.gov/birthcontrol), there are a number of birth control methods that are more than 80% effective

----Female recipients of child-bearing potential must consult with their physician and determine the most suitable method(s) from this list to be used for 18 months after the first dose of study therapy.

Donor:

• Meets institutional selection criteria for organ and bone marrow donation:

--All donors will be screened and tested in accordance with:

• (i) FDA 21 CRF 1271.85 requirements for donors of human cells, tissues, and cellular- and tissue-based products (HCT/P); and

• (ii) standards for living kidney donors testing for infection established by the United Network for Organ Sharing (UNOS).

• Ability to understand and provide informed consent for all study procedures including kidney transplant and bone marrow harvest.

Exclusion Criteria:

Recipient:

• History of any immunodeficiency syndrome (including Human Immunodeficiency Virus-1 (HIV-1) and HIV-2);

• Positive anti-Hepatitis C Virus (HCV) Polymerase Chain Reaction (PCR), anti-Hepatitis C Virus (HBV) PCR, or HBV surface antigen;

• History of malignancy within 5 years of enrollment or any history of hematogenous malignancy or lymphoma; --Exception: Participants with curatively treated non-melanomatous skin cancer or curatively treated cervical carcinoma in situ may be enrolled.

• Underlying renal disease with high likelihood of recurrence, including but not limited to:

• primary focal segmental glomerulosclerosis (FSGS),

• Type I or II membranoproliferative glomerulonephritis (MPGN),

• hemolytic-uremic syndrome and

• thrombotic thrombocytopenic purpura (HUS/TTP) syndrome. ---Subject(s) with end-stage renal disease (ESRD) of unknown etiology and/or has no histologically confirmed diagnosis, may be enrolled into the study as long as there are no clinical signs or symptoms consistent with excluded clinical diagnoses.

• History of active M. tuberculosis:

--Participants with a history of latent M. tuberculosis (LTB) as defined by positive testing for tuberculosis using an approved IGRA blood test, such as QuantiFERON®-Gold TB or T-SPOT-TB assay must:

• have completed treatment for LTB and

• have a negative chest x-ray. ----All participants will undergo IGRA testing for M tuberculosis within 3 months prior to transplant.

• Current or historical evidence of donor-specific antibody;

• Immunosuppressive drug therapy within one year prior to enrollment.

• May not be taking or have taken prednisone, cyclosporine A, tacrolimus, azathioprine, Mycophenolate Mofetil (MMF), cyclophosphamide, methotrexate, infliximab, etanercept, or other agents which have a primary therapeutic effect of immunosuppression in the year prior to transplantation.

• May not have taken depletional anti-lymphocyte agents at any time.

---Exceptions:

• Short (≤ 30 days) courses of topical or inhaled steroids are permitted, as are

• Short oral or parental pulses for a documented hypersensitivity reaction.

• Active autoimmune disease requiring ongoing immunosuppressive therapy or other conditions in which there is an anticipated need for immunosuppressive maintenance therapy;

• Uncompensated congestive heart failure, pulmonary edema, or symptomatic pulmonary hypertension;

• Active severe infection within a month of the screening visit;

• Use of an investigational drug within 30 days of the screening visit;

• Presence of any medical condition that the investigator deems incompatible with trial participation; or

• Inability or unwillingness to comply with protocol monitoring and therapy.

Donor:

• History of blood donation to the recipient;

• Evidence of prior Cytomegalovirus (CMV) infection if the recipient is CMV negative;

• History of HIV-1/HIV-2 infection;

• Positive HCV PCR, HBV PCR or HBV surface antigen;or

• Presence of any medical condition that the investigator deems incompatible with trial participation.