Renal FailurePhase 1/2NCT00498160
Induction of Donor Specific Tolerance in Recipients of Live Donor Kidney Allografts by Donor Stem Cell Infusion
A Phase 1/2 study testing Enriched Hematopoietic Stem Cell Infusion in people with Renal Failure, run by Talaris Therapeutics Inc. at 2 sites in United States.
Trial summary
The goal of this research study is to establish chimerism and avoid graft-versus-host disease in patients with kidney failure allowing a reduction or cessation of immune-suppressive therapy. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Renal Failure
- What is being tested?
- Enriched Hematopoietic Stem Cell Infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2005to Dec 2024
- Phase
- Phase 1/2
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be between the ages of 18 and 65 years and meet the institution's criteria for renal transplantation for end-organ failure
- Patient is receiving first renal transplant
- Patient is receiving a renal transplant only
- The crossmatch is negative between donor and recipient
- Women who are of child bearing potential must have a negative pregnancy test (urine test is acceptable) within 48 hours of initiating total body irradiation (TBI) and agree to use reliable contraception for 1 year following transplant
- Note: The subjects do not need to be local residents in order to be eligible for this trial, but must be willing to reside in the area, or within a four hour drive, for the first three months of the protocol so that we can monitor them closely in the early post transplant period. As long as there is insurance or funding that will cover the cost of the transplant and any research related complications, it is not necessary for the subjects to be US citizens to participate in this trial.
Who cannot join
- Clinically active bacterial, fungal, viral or parasitic infection
- Pregnancy
- Clinical or serologic evidence of viral infection which would preclude the recipient from receiving a kidney transplant
- Previous radiation therapy at a dose which would preclude TBI
- Positive crossmatch between donor and recipient
- Evidence for immunologic memory against donor
- BMI >35 or <18
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Northwestern Memorial Hospital
Chicago, Illinois, 60611
University of Louisville
Louisville, Kentucky, 40202
About this study
Official title: Induction of Donor Specific Tolerance in Recipients of Living Kidney Allografts by Donor FCRx Infusion
The goal of this research study is to establish chimerism and avoid graft-versus-host disease in patients with kidney failure allowing a reduction or cessation of immune-suppressive therapy.
Read the detailed description
At the present time, kidney transplant recipients must take anti-rejection medication to prevent rejection of the donated kidney. Even with this medication, chronic rejection is the most common cause of late graft loss. The anti-rejection agents themselves are significantly toxic, with side effects including kidney damage, infection and an increased incidence of cancer. The goal of this study is to allow the patient to develop "tolerance" to the transplanted kidney while maintaining a competent immune system. Tolerance enables the transplant recipient's body to recognize the transplanted organ as self rather than foreign tissue. The recipient will not try to reject the donor kidney and the need for anti-rejection medication could be dramatically decreased or eliminated entirely. To accomplish this, patients in this study will receive specially treated bone marrow taken from their kidney donor. Bone marrow transplant has been shown in animal studies and in humans to induce tolerance following organ transplant.
Two factors limit the application of donor marrow transplant to induce tolerance: 1) preparing the patient for transplant (conditioning); and 2) graft-versus-host disease (GVHD). Traditional conditioning destroys the recipient's immune system and requires that the marrow transplant be successful because the patient is unable to fight off infection if the donor cells do not survive. GVHD occurs when donor immune cells recognize the recipient's cells as foreign tissue and attack them. Severe GVHD can result in death. This study utilizes a new approach to conditioning which leaves the patient's immune system intact. The transplant product is depleted of GVHD-producing cells but retains tolerance-promoting facilitating cells, which are intended to ensure the donor and recipient cells coexists peacefully, a state called mixed chimerism. The toxicity of conditioning and transplantation is significantly reduced.
In this study, we will determine the appropriate cell dose to safely establish mixed chimerism following partial conditioning in living donor or deceased donor kidney transplant recipients. The study takes a gradual approach to increasing the cell dose to achieve mixed chimerism. We believe this study will provide a breakthrough in the approach to kidney transplantation. Our goal is to evaluate the potential of safely establishing mixed chimerism to induce tolerance following kidney transplant and reduce or eliminate the need for anti-rejection therapy.
- Conditions
- Renal Failure
- Being tested
- Enriched Hematopoietic Stem Cell Infusion
- Keywords
- Kidney transplant, Tolerance, Marrow/stem cell transplant
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enriched Hematopoietic Stem Cell InfusionBiological
Enriched Hematopoietic Stem Cell Infusion
| Study group | Role | What they receive |
|---|---|---|
| Living or Deceased Donor Kidney Allograft | Experimental | Recipients with the need for a living kidney allograft are treated with an enriched hematopoetic stem cell infusion from the same living donor. Recipients with the need for a deceased donor kidney allograft are treated with an enriched hematopoetic stem cell infusion from the same deceased donor Receives: Biological: Enriched Hematopoietic Stem Cell Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Level of Donor Chimerism from Enriched Hematopoietic Stem Cell Engraftment
Tests are done at key time points to monitor for donor chimerism by evaluating presence of bone marrow-derived hematopoietic stem cells.
Measured: one month to three years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2007 (estimated)
- Study startJan 2005
- Primary completionAug 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renal FailureStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Talaris Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Northwestern University
- Responsible party
- Sponsor
- Investigators
- Suzanne T Ildstad, MD, Study director, Talaris Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00498160
- Sponsor's protocol ID
- ICT-7392-041698
- Status last verified
- Jul 2022
- First submitted
- 6 Jul 2007
- Last updated
- 18 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
- Expanded access
- Available
Publications
Senev A, Tambur AR, Kosmoliaptsis V, Copley HC, Garcia-Sanchez C, Usenko C, Ildstad ST, Leventhal JR. HLA molecular mismatches and induced donor-specific tolerance in combined living donor kidney and hematopoietic stem cell transplantation. Front Immunol. 2024 Mar 27;15:1377535. doi: 10.3389/fimmu.2024.1377535. eCollection 2024.
PubMed 38601147
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Induction of Donor Specific Tolerance in Recipients of Living Kidney Allografts by Donor FCRx Infusion
- ClinicalTrials.gov ID
- NCT00498160
- Acronym / sponsor ID
- ICT-7392-041698
- Conditions
- Renal Failure
- Keywords
- Kidney transplant, Tolerance, Marrow/stem cell transplant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Talaris Therapeutics Inc.Industry (pharma, biotech, devices)
- Collaborators
- Northwestern University
- Study start
- Jan 2005 (actual)
- Primary completion
- Aug 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 9 Jul 2007 (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 goal of this research study is to establish chimerism and avoid graft-versus-host disease in patients with kidney failure allowing a reduction or cessation of immune-suppressive therapy.
Detailed description
At the present time, kidney transplant recipients must take anti-rejection medication to prevent rejection of the donated kidney. Even with this medication, chronic rejection is the most common cause of late graft loss. The anti-rejection agents themselves are significantly toxic, with side effects including kidney damage, infection and an increased incidence of cancer. The goal of this study is to allow the patient to develop "tolerance" to the transplanted kidney while maintaining a competent immune system. Tolerance enables the transplant recipient's body to recognize the transplanted organ as self rather than foreign tissue. The recipient will not try to reject the donor kidney and the need for anti-rejection medication could be dramatically decreased or eliminated entirely. To accomplish this, patients in this study will receive specially treated bone marrow taken from their kidney donor. Bone marrow transplant has been shown in animal studies and in humans to induce tolerance following organ transplant.
Two factors limit the application of donor marrow transplant to induce tolerance: 1) preparing the patient for transplant (conditioning); and 2) graft-versus-host disease (GVHD). Traditional conditioning destroys the recipient's immune system and requires that the marrow transplant be successful because the patient is unable to fight off infection if the donor cells do not survive. GVHD occurs when donor immune cells recognize the recipient's cells as foreign tissue and attack them. Severe GVHD can result in death. This study utilizes a new approach to conditioning which leaves the patient's immune system intact. The transplant product is depleted of GVHD-producing cells but retains tolerance-promoting facilitating cells, which are intended to ensure the donor and recipient cells coexists peacefully, a state called mixed chimerism. The toxicity of conditioning and transplantation is significantly reduced.
In this study, we will determine the appropriate cell dose to safely establish mixed chimerism following partial conditioning in living donor or deceased donor kidney transplant recipients. The study takes a gradual approach to increasing the cell dose to achieve mixed chimerism. We believe this study will provide a breakthrough in the approach to kidney transplantation. Our goal is to evaluate the potential of safely establishing mixed chimerism to induce tolerance following kidney transplant and reduce or eliminate the need for anti-rejection therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Living or Deceased Donor Kidney Allograft | Experimental | Biological: Enriched Hematopoietic Stem Cell InfusionRecipients with the need for a living kidney allograft are treated with an enriched hematopoetic stem cell infusion from the same living donor. Recipients with the need for a deceased donor kidney allograft are treated with an enriched hematopoetic stem cell infusion from the same deceased donor |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients must be between the ages of 18 and 65 years and meet the institution's criteria for renal transplantation for end-organ failure
- Patient is receiving first renal transplant
- Patient is receiving a renal transplant only
- The crossmatch is negative between donor and recipient
- Women who are of child bearing potential must have a negative pregnancy test (urine test is acceptable) within 48 hours of initiating total body irradiation (TBI) and agree to use reliable contraception for 1 year following transplant
Key exclusion criteria (7 listed)
- Clinically active bacterial, fungal, viral or parasitic infection
- Pregnancy
- Clinical or serologic evidence of viral infection which would preclude the recipient from receiving a kidney transplant
- Previous radiation therapy at a dose which would preclude TBI
- Positive crossmatch between donor and recipient
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 |
|---|---|---|
| Enriched Hematopoietic Stem Cell InfusionEnriched Hematopoietic Stem Cell Infusion | Biological | Living or Deceased Donor Kidney Allograft |
Primary outcome
Level of Donor Chimerism from Enriched Hematopoietic Stem Cell Engraftment
Time frame: one month to three years
Tests are done at key time points to monitor for donor chimerism by evaluating presence of bone marrow-derived hematopoietic stem cells.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2022.
- Derived from this study: PubMed 38601147Senev A, Tambur AR, Kosmoliaptsis V, Copley HC, Garcia-Sanchez C, Usenko C, Ildstad ST, Leventhal JR. HLA molecular mismatches and induced donor-specific tolerance in combined living donor kidney and hematopoietic stem cell transplantation. Front Immunol. 2024 Mar 27;15:1377535. doi: 10.3389/fimmu.2024.1377535. eCollection 2024.
- Individual participant dataSharing planned: Undecided
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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.
Suzanne T Ildstad, MD study director
Talaris Therapeutics Inc.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Enriched Hematopoietic Stem Cell Infusion in people with Renal Failure, run by Talaris Therapeutics Inc. 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 6 inclusion and 7 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 Jul 2022. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Level of Donor Chimerism from Enriched Hematopoietic Stem Cell Engraftment (time frame: one month to three years). 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 NCT00498160, which also lists 1 linked publication.
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 Jul 2022.