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Kidney TransplantationPhase 1TEACHNCT03504241

Tolerance by Engaging Antigen During Cellular Homeostasis

A Phase 1 study testing Donor-derived Mesenchymal Stromal Cells, alemtuzumab and belatacept in people with Kidney Transplantation and Renal Transplantation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 19 years and older
What is being tested?
Donor-derived Mesenchymal Stromal Cells, alemtuzumab and belatacept
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteUnited States
Study dates
30 Jul 2018to 16 Sep 2025
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Recipient:
  • Adult candidates of an human leukocyte antigen (HLA)-non-identical, living-donor kidney transplant:
  • --Candidates had to 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 was CMV positive;
  • For women of child bearing potential:
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  • 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 were a number of birth control methods that were more than 80% effective
  • Female recipients of child-bearing potential had to 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:
  • Met institutional selection criteria for organ and bone marrow donation:
  • --All donors were 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.

Who cannot join

  • 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 could be enrolled.
  • Underlying renal disease with high likelihood of recurrence, including but not limited to:
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  • 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 who had no histologically confirmed diagnosis, could be enrolled into the study as long as there were 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 had to:
  • have completed treatment for LTB and
  • have a negative chest x-ray.
  • ----All participants underwent 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 have been taking or have taken prednisone, cyclosporine A, tacrolimus, azathioprine, Mycophenolate Mofetil (MMF), cyclophosphamide, methotrexate, infliximab, etanercept, or other agents which had 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 were permitted, as were
  • Short oral or parental pulses for a documented hypersensitivity reaction.
  • Active autoimmune disease requiring ongoing immunosuppressive therapy or other conditions in which there was 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 deemed 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 was 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 deemed incompatible with trial participation.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Duke University Health System

    Durham, North Carolina, 27710

Other trials in United States

About this study

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

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 was to determine if:

  • it was safe to give mesenchymal stromal cells (MSCs) to kidney transplant recipients, and
  • the combination of the immunosuppressive (anti-rejection) study drugs plus the MSCs could 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".
Read the detailed description

Background:

The most common problem following a kidney transplant is the development of acute or chronic rejection. Rejection is an immunologic reaction in which the body's immune system recognizes the transplanted organ as foreign and may attack it.

In order to prevent organ rejection, patients receiving an allograft (a graft transplanted between genetically non-identical individuals of the same species) are required to take anti-rejection (immunosuppressive) therapy. These medications function by lowering the body's natural immune response and may be associated with significant side effects, ranging from infections to cancer.

Study:

This was a single-center, open-label, dose-escalation clinical trial. Originally, 6 adult recipients of Human Leukocyte Antigen (HLA)-non-identical, living-donor renal allografts were to receive induction therapy with alemtuzumab followed by maintenance therapy with sirolimus and belatacept; in addition, participants were to receive donor-derived MSCs in three escalating dose cohorts. However, study enrollment was terminated before recruitment began for Cohort 3.

Participants in Cohorts 1 and 2 were assigned to receive 12 infusions of donor-derived MSCs beginning on Day 42 post-transplant and every 4 weeks beginning on Day 56 post-transplant, with a minimum of 7 days between the first and second MSC infusions.

The primary objective was to determine whether immune reconstitution after lymphocyte depletion in the setting of co-stimulatory blockade and systemic MSC-derived donor antigen could promote operational tolerance in recipients of kidney allografts.

Participants were evaluated for eligibility for sirolimus withdrawal any time between Week 52 and Week 104 post-transplant. Participants who successfully completed sirolimus withdrawal remained on belatacept monotherapy for at least 24 weeks before being assessed for eligibility to discontinue belatacept. Participants who successfully completed Immunosuppression Withdrawal (ISW) then underwent 24 weeks of high-frequency follow-up followed by 132 weeks of standard follow-up.

Study participation could continue for up to approximately 6 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.
Being tested
Donor-derived Mesenchymal Stromal Cells, alemtuzumab, belatacept, sirolimus, mycophenolate mofetil
Keywords
mesenchymal stromal cells (MSCs), anti-rejection drugs, operational tolerance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Donor-derived Mesenchymal Stromal CellsBiological

    Also called Donor-derived MSCs, human bone marrow derived MSCs, hBM-MSC, EPIC-MSC-ITN2015-IVF-0X

    These MSCs were 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.

  • alemtuzumabDrug

    Also called Campath®, Lemtrada®

    Alemtuzumab, 30 mg, was given once intravenously (IV) over three hours. The infusion of alemtuzumab began within 24 hours of transplantation surgery and was given prior to the first dose of belatacept.

  • belataceptDrug

    Also called Nulojix®, LEA29Y

    Belatacept was 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 was 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 was evaluated for belatacept discontinuation.

  • sirolimusDrug

    Also called Rapamune®

    Rapamune® (sirolimus) (Wyeth Pharmaceuticals Inc., Philadelphia, PA) was 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 experienced grade 3 sirolimus toxicity underwent dose reduction.

  • mycophenolate mofetilDrug

    Also called CellCept®

    Per protocol and was only permitted in cases of sirolimus intolerance.

  • mycophenolate acidDrug

    Also called Myfortic®

    Per protocol and was only permitted in cases of sirolimus intolerance.

  • prednisoneDrug

    Also called corticosteroid

    Per protocol and was only permitted in cases of sirolimus intolerance.

Study groups in NCT03504241
Study groupRoleWhat they receive
MSCs 10^4 cells/kg+anti-rejection drugsExperimentalThe first dosing cohort of 2 participants received 12 infusions of 10^4 donor-derived Mesenchymal Stromal Cells (MSCs) cells/kg every 4-weeks. (Cohort 1)
Receives: Biological: Donor-derived Mesenchymal Stromal Cells; Drug: alemtuzumab; Drug: belatacept; Drug: sirolimus; Drug: mycophenolate mofetil; Drug: mycophenolate acid; Drug: prednisone
MSCs 10^5 cells/kg+anti-rejection drugsExperimentalCohort 2, consisting of 2 participants receive 12 infusions of 10^5 cells/kg every 4-weeks.
Receives: Biological: Donor-derived Mesenchymal Stromal Cells; Drug: alemtuzumab; Drug: belatacept; Drug: sirolimus; Drug: mycophenolate mofetil; Drug: mycophenolate acid; Drug: prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of Participants Who Achieve Operational Tolerance

    Operational tolerance (to their kidney transplant) defined by participant remaining off all immunosuppression for 52 weeks after completion of Immunosuppression Withdrawal (ISW) with:

    • No evidence of biopsy-proven allograft rejection after initiation of ISW;
    • Acceptable renal function, defined as an estimated GFR > 60 ml/min/1.73cm^2 calculated using the CKD-EPI equation or a serum creatinine that has increased no more than 25% above baseline, as assessed at the week 52 visit after completion of ISW;
    • No evidence of sustained transplant renal derived pathologic proteinuria, defined as a persistent protein creatinine ratio of greater than 0.5; and
    • No Donor Specific Antibodies (DSA) at any time after completion of ISW.

    Measured: 52 weeks after completion of Immunosuppression Withdrawal (ISW); ISW was initiated between Weeks 52 and 104 post-transplant and was required to be completed within 52 weeks of initiation

Secondary outcomes (19)

  1. Proportion of Participants Who Remain Off Immunosuppression

    Proportion of participants who remained off all immunosuppression from completion of Immunosuppression Withdrawal (ISW) through the end of study participation. Participants who did not complete ISW were counted as not remaining off immunosuppression.

    Measured: From completion of ISW through end of study participation, up to 156 weeks after ISW completion (up to approximately 5 years)

  2. Proportion of Participants Who Return to Immunosuppression

    Proportion of participants who resumed immunosuppressive therapy following initiation of Immunosuppression Withdrawal (ISW). Participants who did not complete ISW were counted as having returned to immunosuppression.

    Measured: From completion of ISW through end of study participation, up to 156 weeks after ISW completion (up to approximately 5 years)

  3. Proportion of Participants Who Achieve Belatacept Monotherapy

    Proportion of participants who remained on belatacept as the sole maintenance immunosuppressive regimen for 48 weeks, with no biopsy-proven allograft rejection, acceptable renal function, no sustained transplant renal-derived pathologic proteinuria, and no donor-specific antibodies (DSA) while on belatacept monotherapy. Participants who did not achieve belatacept sole maintenance were counted as not achieving belatacept monotherapy.

    Measured: From the last dose of sirolimus through 48 weeks of belatacept monotherapy (up to approximately 2 years)

  4. Proportion of Participants Who Die

    Proportion of recipient participants in the Safety Sample who died during study participation. The Safety Sample included participants who provided informed consent and received any study therapy, including alemtuzumab, sirolimus, belatacept, or MSC infusions.

    Measured: From kidney transplantation through completion or discontinuation of study participation (up to approximately 6 years)

  5. Time From Transplant to the First Episode of Rejection

    Kaplan-Meier analysis of time from kidney transplantation to the first episode of biopsy-proven or treated kidney allograft rejection. Recipient participants without a rejection event were censored at the date of last contact or end of study.

    Measured: From kidney transplantation to first rejection or end of study follow-up (up to approximately 6 years)

  6. Proportion of Participants Who Develop Donor-Specific Antibodies (DSA) During Immunosuppression Withdrawal

    Proportion of recipient participants who developed donor-specific antibodies (DSA) during Immunosuppression Withdrawal (ISW). DSA with a mean fluorescence intensity (MFI) >1000 was considered abnormal and was verified by repeat testing within 14 days.

    Measured: From initiation through completion of Immunosuppression Withdrawal (ISW), up to 52 weeks after ISW initiation

  7. Incidence Rate of Donor-Specific Antibodies (DSA) During Immunosuppression Withdrawal

    Incidence rate of donor-specific antibody (DSA) development during Immunosuppression Withdrawal (ISW), expressed per 100 participant-years. ISW participant-years were calculated from ISW initiation to the first DSA for participants who developed DSA, and from ISW initiation to the end of ISW for participants who did not develop DSA.

    Measured: From initiation through completion of Immunosuppression Withdrawal (ISW), up to 52 weeks after ISW initiation

  8. Proportion of Participants Who Develop Donor-Specific Antibodies (DSA) During Study Participation

    Proportion of recipient participants who developed donor-specific antibodies (DSA) at any time during study participation. DSA with a mean fluorescence intensity (MFI) >1000 was considered abnormal and was verified by repeat testing within 14 days.

    Measured: From informed consent through completion or discontinuation of study participation (up to approximately 6 years)

  9. Incidence Rate of Donor-Specific Antibody (DSA) Development During Study Participation

    Incidence rate of donor-specific antibody (DSA) development during study participation, expressed per 100 participant-years. Participant-years were calculated from informed consent to the first DSA for participants who developed DSA, and from informed consent to study withdrawal or completion for participants who did not develop DSA. DSA with a mean fluorescence intensity (MFI) >1000 was considered abnormal and was verified by repeat testing within 14 days.

    Measured: From informed consent through completion or discontinuation of study participation (up to approximately 6 years)

  10. Proportion of Participants With Adverse Events Attributable to Mesenchymal Stromal Cell (MSC) Administration

    Proportion of MSC-treated recipient participants who experienced at least one adverse event (AE) considered attributable to MSC administration. An AE was considered related if it was assessed as possibly related or related. For serious AEs, the DAIT medical monitor assessment of relationship was used; for non-serious AEs, the site investigator assessment was used.

    Measured: From first MSC infusion through completion or discontinuation of study participation (up to approximately 6 years)

  11. Proportion of Participants With Select Adverse Events (AEs), by Type

    Proportion of recipient participants who experienced at least one prespecified select adverse event (AE), presented by AE type. Select AEs included infection of Grade 3 or higher, malignancy, and wound complications, defined as wound dehiscence, hernia, or lymphocele.

    Measured: From kidney transplantation through completion or discontinuation of study participation (up to approximately 6 years)

  12. Duration of Grade 3 or Higher Infection

    Duration, in days, of Grade 3 or higher infection among recipient participants with an evaluable infection duration. Adverse event severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03.

    Measured: From kidney transplantation through completion or discontinuation of study participation (up to approximately 6 years)

  13. Duration of Malignancy

    Duration, in days, of malignancy among recipient participants with an evaluable malignancy duration.

    Measured: From kidney transplantation through completion or discontinuation of study participation (up to approximately 6 years)

  14. Duration of Wound Complications

    Duration, in days, of wound complications among recipient participants with an evaluable wound complication duration. Wound complications were defined as wound dehiscence, hernia, or lymphocele.

    Measured: From kidney transplantation through completion or discontinuation of study participation (up to approximately 6 years)

  15. Proportion of Participants Who Developed Post-Transplant Diabetes Mellitus (PTDM)

    Proportion of recipient participants who developed new-onset post-transplant diabetes mellitus (PTDM) during study participation.

    Measured: From kidney transplantation through completion or discontinuation of study participation (up to approximately 6 years)

  16. Proportion of Participants With Acute T-Cell-Mediated Rejection, by Banff Grade

    Proportion of recipient participants who experienced acute T-cell-mediated kidney allograft rejection, categorized as Banff Grade IA, IB, IIA, IIB, or III according to the Banff 2017 criteria.

    Measured: From kidney transplantation through completion or discontinuation of study participation (up to approximately 6 years)

  17. Proportion of Participants With Antibody-Mediated Rejection, by Type

    Proportion of recipient participants who experienced antibody-mediated kidney allograft rejection, categorized as acute/active or chronic/active according to the Banff 2017 criteria.

    Measured: From kidney transplantation through completion or discontinuation of study participation (up to approximately 6 years)

  18. Duration of Kidney Allograft Rejection

    Duration, in days, of kidney allograft rejection among recipient participants with an evaluable rejection duration. Rejection events were classified according to the Banff 2017 criteria.

    Measured: From kidney transplantation through completion or discontinuation of study participation (up to approximately 6 years)

  19. Proportion of Participants With Biopsy-Proven Chronic Allograft Nephropathy/Interstitial Fibrosis and Tubular Atrophy (IF/TA)

    Proportion of recipient participants with biopsy-proven chronic allograft nephropathy/interstitial fibrosis and tubular atrophy (IF/TA) during study participation.

    Measured: From kidney transplantation through completion or discontinuation of study participation (up to approximately 6 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Apr 2018
  2. Study start30 Jul 2018
  3. Primary completion6 Sep 2023
  4. Study completion16 Sep 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03504241
Sponsor's protocol ID
DAIT ITN062ST
Other IDs
UM1AI109565, NIAID CRMS ID#: 20676
Acronym
TEACH
Status last verified
Oct 2026
First submitted
12 Apr 2018
Last updated
29 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The plan is to share data upon completion of the study in ImmPort, a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Donor-derived Mesenchymal Stromal Cells, alemtuzumab and belatacept in people with Kidney Transplantation and Renal Transplantation, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Participants Who Achieve Operational Tolerance (time frame: 52 weeks after completion of Immunosuppression Withdrawal (ISW); ISW was initiated between Weeks 52 and 104 post-transplant and was required to be completed within 52 weeks of initiation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03504241.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.

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