ESRDPhase 1NCT01165762
Combined Blood Stem Cell and Kidney Transplant of One Haplotype Match Living Donor Pairs.
A Phase 1 study testing Immune Tolerance in people with ESRD, run by Everett Meyer at 2 sites in United States.
Trial summary
The Stanford Medical Center Program in Multi-Organ Transplantation and the Division of Bone marrow Transplantation are enrolling patients into a research study to determine if donor stem cells given after a living related one Haplotype match kidney transplantation will change the immune system such that… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- ESRD
- What is being tested?
- Immune Tolerance
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesUnited States
- Study dates
- 14 Jul 2010to 14 Jun 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- All consenting adults who are 18 to 60 years, living donor transplant candidates and have a haplotype related living donor or > 2 HLA antigen matched, unrelated, living donor (including at least one HLA-DR antigen match plus at least one antigen match of either HLA-A or HLA-B).
- Patients who agree to participate in the study and sign an Informed Consent.
- Patients who have no known contraindication to administration of rabbit ATG or radiation.
- Males and females of reproductive potential who agree to practice a reliable form of contraception for at least 24 months post-transplant.
- ABO compatible.
Who cannot join
- Previous treatment with rabbit ATG or a known allergy to rabbit proteins.
- History of malignancy with the exception of non-melanoma skin malignancies.
- Pregnant women or nursing mothers.
- Serological evidence of HIV, Hepatitis B or Hepatitis C infection.
- Seronegative for Epstein-Barr virus, if donor is seropositive.
- Leukopenia (with a white blood cell count < 3000/mm3) or thrombocytopenia (with a platelet count < 100,000/mm3).
Show all 9Show fewer
- Panel Reactive Antibody greater than 80% or demonstration of donor specific antibody (DSA).
- Prior organ transplantation.
- High risk of primary kidney disease recurrence (e.g atypical HUS). However, patients with primary FSGS will not be excluded.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Wisconsin
Madison, Wisconsin, 53792-1690
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+ and T-cell Transfusion in HLA Haplotype Match Living Donor Kidney Transplantation
The Stanford Medical Center Program in Multi-Organ Transplantation and the Division of Bone marrow Transplantation are enrolling patients into a research study to determine if donor stem cells given after a living related one Haplotype match kidney transplantation will change the immune system such that immunosuppressive drugs can be completely withdrawn.
Read the detailed description
The goal of this study is for the recipients of a living related kidney transplant of one HLA haplotype to be withdrawn of immunosuppressive medication and become "tolerant "to their kidney graft. The recipient will receive a conditioning regimen composed of low dose radiation to the lymphoid tissue (total lymphoid irradiation, TLI) and anti-thymocyte globulin (ATG) at the time of transplant. They will then be infused with purified "stem cell" and T-cell from their kidney donors 2 weeks after the transplant to try to achieve mixed chimerism of their white blood cells with the donor (the recipient would have a mixture some of the with blood cells of the donor and theirs in their blood). The kidney donor has to provide peripheral stem cell 6-8 weeks before kidney donation. It is an outpatient procedure done using peripheral veins after treatment with G-CSF (filgrastim).Immunosuppressive medication will be decreased gradually and possibly stopped by 1 1/2 year after the transplantation if the recipient meets withdrawing criteria (persistence of mixed chimerism more than 18 months, no episode of rejection and no rejection on surveillance kidney biopsy). Potential candidates need to be approved for kidney transplant and available for close follow-up at Stanford University Medical Center.
- Conditions
- ESRD
- Being tested
- Immune Tolerance
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immune ToleranceDrug
Also called Kidney transplantation
Immune tolerance Kidney and hematopoietic cell transplantation with a conditioning regimen of total lymphoid irradiation and antithymocyte globulin followed by immunosuppressive drugs for 18 months. Immunosuppressive drugs are stopped if stable chimerism is achieved and there is no rejection of the transplant kidney.
The IDE used in this study is the column used for hematopoietic cell sorting.
| Study group | Role | What they receive |
|---|---|---|
| Immune Tolerance, Kidney transplantation | Experimental | Induction of immune tolerance in Haplotype matched living donor kidney transplantation. Receives: Drug: Immune Tolerance |
What is being measured
The primary outcome is the main question the study is designed to answer.
Long term freedom from transplant immunosuppressive drugs, safety, rate of infection, graft survival and patient survival.
Subjects on study will have tapering of the immunosuppressive medication and withdrawal of the immunosuppressive medication if withdrawal criteria are met.
Measured: 5 years and indefinitely if possible
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2010 (estimated)
- Study start14 Jul 2010
- Primary completion14 Jun 2024 (estimated)
- Study completion14 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for ESRDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Everett Meyer
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor-investigator, Everett Meyer, Stanford University
- Investigators
- Stephan Busque, MD,MS, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01165762
- Sponsor's protocol ID
- SU-06232010-6408
- Other IDs
- P01HL075462
- Status last verified
- Jun 2023
- First submitted
- 13 Jul 2010
- Last updated
- 18 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Millan MT, Shizuru JA, Hoppe RT, Lowsky R, Engleman EG, Strober S. Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med. 2008 Jan 24;358(4):362-8. doi: 10.1056/NEJMoa074191.
PubMed 18216356Scandling JD, Busque S, Shizuru JA, Engleman EG, Strober S. Induced immune tolerance for kidney transplantation. N Engl J Med. 2011 Oct 6;365(14):1359-60. doi: 10.1056/NEJMc1107841. No abstract available.
PubMed 21991976Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Sarwal M, Millan MT, Shizuru JA, Lowsky R, Engleman EG, Strober S. Tolerance and withdrawal of immunosuppressive drugs in patients given kidney and hematopoietic cell transplants. Am J Transplant. 2012 May;12(5):1133-45. doi: 10.1111/j.1600-6143.2012.03992.x. Epub 2012 Mar 8.
PubMed 22405058Jensen KP, Hongo DA, Ji X, Zheng P, Pawar R, Wu TH, Busque S, Scandling JD, Shizuru JA, Lowsky R, Shori A, Dutt S, Waters J, Saraswathula A, Baker J, Tamaresis JS, Lavori P, Negrin R, Maecker H, Engleman EG, Meyer E, Strober S. Development of immunosuppressive myeloid cells to induce tolerance in solid organ and hematopoietic cell transplant recipients. Blood Adv. 2021 Sep 14;5(17):3290-3302. doi: 10.1182/bloodadvances.2020003669.
PubMed 34432869
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+ and T-cell Transfusion in HLA Haplotype Match Living Donor Kidney Transplantation
- ClinicalTrials.gov ID
- NCT01165762
- Acronym / sponsor ID
- SU-06232010-6408
- Conditions
- ESRD
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Everett MeyerUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 14 Jul 2010 (actual)
- Primary completion
- 14 Jun 2024 (estimated)
- Study completion
- 14 Jun 2025 (estimated)
- First posted
- 20 Jul 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Stanford Medical Center Program in Multi-Organ Transplantation and the Division of Bone marrow Transplantation are enrolling patients into a research study to determine if donor stem cells given after a living related one Haplotype match kidney transplantation will change the immune system such that immunosuppressive drugs can be completely withdrawn.
Detailed description
The goal of this study is for the recipients of a living related kidney transplant of one HLA haplotype to be withdrawn of immunosuppressive medication and become "tolerant "to their kidney graft. The recipient will receive a conditioning regimen composed of low dose radiation to the lymphoid tissue (total lymphoid irradiation, TLI) and anti-thymocyte globulin (ATG) at the time of transplant. They will then be infused with purified "stem cell" and T-cell from their kidney donors 2 weeks after the transplant to try to achieve mixed chimerism of their white blood cells with the donor (the recipient would have a mixture some of the with blood cells of the donor and theirs in their blood). The kidney donor has to provide peripheral stem cell 6-8 weeks before kidney donation. It is an outpatient procedure done using peripheral veins after treatment with G-CSF (filgrastim).Immunosuppressive medication will be decreased gradually and possibly stopped by 1 1/2 year after the transplantation if the recipient meets withdrawing criteria (persistence of mixed chimerism more than 18 months, no episode of rejection and no rejection on surveillance kidney biopsy). Potential candidates need to be approved for kidney transplant and available for close follow-up at Stanford University Medical Center.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Immune Tolerance, Kidney transplantation | Experimental | Drug: Immune ToleranceInduction of immune tolerance in Haplotype matched living donor kidney transplantation. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- All consenting adults who are 18 to 60 years, living donor transplant candidates and have a haplotype related living donor or > 2 HLA antigen matched, unrelated, living donor (including at least one HLA-DR antigen match plus at least one antigen match of either HLA-A or HLA-B).
- Patients who agree to participate in the study and sign an Informed Consent.
- Patients who have no known contraindication to administration of rabbit ATG or radiation.
- Males and females of reproductive potential who agree to practice a reliable form of contraception for at least 24 months post-transplant.
- ABO compatible.
Key exclusion criteria (9 listed)
- Previous treatment with rabbit ATG or a known allergy to rabbit proteins.
- History of malignancy with the exception of non-melanoma skin malignancies.
- Pregnant women or nursing mothers.
- Serological evidence of HIV, Hepatitis B or Hepatitis C infection.
- Seronegative for Epstein-Barr virus, if donor is seropositive.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Immune ToleranceAlso: Kidney transplantationImmune tolerance Kidney and hematopoietic cell transplantation with a conditioning regimen of total lymphoid irradiation and antithymocyte globulin followed by immunosuppressive drugs for 18 months. Immunosuppressive drugs are stopped if stable chimerism is achieved and there is no rejection of the transplant kidney. The IDE used in this study is the column used for hematopoietic cell sorting. | Drug | Immune Tolerance, Kidney transplantation |
Primary outcome
Long term freedom from transplant immunosuppressive drugs, safety, rate of infection, graft survival and patient survival.
Time frame: 5 years and indefinitely if possible
Subjects on study will have tapering of the immunosuppressive medication and withdrawal of the immunosuppressive medication if withdrawal criteria are met.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2023.
- Background: PubMed 18216356Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Millan MT, Shizuru JA, Hoppe RT, Lowsky R, Engleman EG, Strober S. Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med. 2008 Jan 24;358(4):362-8. doi: 10.1056/NEJMoa074191.
- Background: PubMed 21991976Scandling JD, Busque S, Shizuru JA, Engleman EG, Strober S. Induced immune tolerance for kidney transplantation. N Engl J Med. 2011 Oct 6;365(14):1359-60. doi: 10.1056/NEJMc1107841. No abstract available.
- Background: PubMed 22405058Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Sarwal M, Millan MT, Shizuru JA, Lowsky R, Engleman EG, Strober S. Tolerance and withdrawal of immunosuppressive drugs in patients given kidney and hematopoietic cell transplants. Am J Transplant. 2012 May;12(5):1133-45. doi: 10.1111/j.1600-6143.2012.03992.x. Epub 2012 Mar 8.
- Derived from this study: PubMed 34432869Jensen KP, Hongo DA, Ji X, Zheng P, Pawar R, Wu TH, Busque S, Scandling JD, Shizuru JA, Lowsky R, Shori A, Dutt S, Waters J, Saraswathula A, Baker J, Tamaresis JS, Lavori P, Negrin R, Maecker H, Engleman EG, Meyer E, Strober S. Development of immunosuppressive myeloid cells to induce tolerance in solid organ and hematopoietic cell transplant recipients. Blood Adv. 2021 Sep 14;5(17):3290-3302. doi: 10.1182/bloodadvances.2020003669.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephan Busque, MD,MS principal investigator
Stanford University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Immune Tolerance in people with ESRD, run by Everett Meyer at 2 sites 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 5 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 18 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Results are not available in the source record.
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?
Long term freedom from transplant immunosuppressive drugs, safety, rate of infection, graft survival and patient survival. (time frame: 5 years and indefinitely if possible). 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 NCT01165762, which also lists 4 linked publications.
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 18 Jun 2023.