Heart TransplantationPhase 1/2NCT00497757
Induction of Donor Specific Tolerance in Recipients of Cardiac Allografts by Donor Stem Cell Infusion
A Phase 1/2 study testing enriched hematopoetic stem cell infusion in people with Heart Transplantation, run by Suzanne T. Ildstad.
Trial summary
The goal of this research study is to establish chimerism and avoid graft-versus-host disease in patients who need a heart transplant. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Heart Transplantation
- What is being tested?
- enriched hematopoetic stem cell infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- No sites listed yet
- Study dates
- Jul 2003to 1 Dec 2016
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must be between the ages of 18 and 70 years and meet the institution's criteria for cardiac transplantation.
- Subjects must have acceptable negative results for infectious disease markers done within two weeks of the bone marrow infusion.
- Subject is receiving a first cardiac transplant.
- Subjects receiving a multi-organ transplant (i.e., heart/kidney) may be included at the discretion of the PI and investigators.
- Note: These multi-organ subjects will have identical criteria with the exception of adequate function of the affected organ to be transplanted (i.e., kidney). They are included in the total of thirty subjects to be transplanted.
- Subject's panel reactive antibody (PRA) is <40. If the patient is plasmapheresed prior to the heart transplant, then the pre-transplant PRA will not be a consideration for inclusion/exclusion.
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- Subject must have a negative crossmatch with the donor.
- Women who are of child bearing potential must have a negative pregnancy test (urine test within 48 hours) before TBI and agree to use reliable contraception for one year following transplant.
- Subject is able to give informed consent.
Who cannot join
- Clinically active bacterial, fungal, viral or parasitic infection
- Pregnancy
- Previous radiation therapy at a dose that would preclude TBI
- Subject is unable to give informed consent
- If the procedures associated with the study (i.e., delivering TBI) would significantly extend the cold ischemia time of the heart, the protocol will be abandoned and the patient will receive a conventional heart transplant.
About this study
Official title: 1) Induction of Donor-Specific Tolerance in Recipients of Cardiac Allografts by Donor Stem Cell Infusion 2) Induction of Donor-Specific Tolerance by Donor Facilitating Cell (FC): Stem Cell Infusion in Recipients of Hepatic Allografts
The goal of this research study is to establish chimerism and avoid graft-versus-host disease in patients who need a heart transplant.
Read the detailed description
At the present time, heart transplant recipients must take anti-rejection medication to prevent rejection of the donated heart. 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 heart 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 heart 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 heart 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 heart 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 heart transplantation. Our goal is to evaluate the potential of safely establishing mixed chimerism to induce tolerance following heart transplant and reduce or eliminate the need for anti-rejection therapy.
- Conditions
- Heart Transplantation
- Being tested
- enriched hematopoetic stem cell infusion
- Keywords
- Marrow/hematopoietic stem cell transplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
enriched hematopoetic stem cell infusionBiological
Enriched Hematopoetic Stem Cell Infusion
| Study group | Role | What they receive |
|---|---|---|
| Cardiac Failure Patients | Experimental | Recipients treated with an enriched hematopoetic stem cell infusion from the heart donor's bone marrow Receives: Biological: enriched hematopoetic stem cell infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Enriched Hematopoetic Stem Cell Engraftment
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 startJul 2003
- Primary completion7 Nov 2011
- Study completion1 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart TransplantationStudies 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
- Model description
- Open label
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Suzanne T. Ildstad
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Suzanne T. Ildstad, University of Louisville
- Investigators
- Suzanne T Ildstad, MD, Study director, University of Louisville
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00497757
- Sponsor's protocol ID
- ICT-7494-041698
- Status last verified
- Aug 2020
- First submitted
- 6 Jul 2007
- Last updated
- 31 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 1) Induction of Donor-Specific Tolerance in Recipients of Cardiac Allografts by Donor Stem Cell Infusion 2) Induction of Donor-Specific Tolerance by Donor Facilitating Cell (FC): Stem Cell Infusion in Recipients of Hepatic Allografts
- ClinicalTrials.gov ID
- NCT00497757
- Acronym / sponsor ID
- ICT-7494-041698
- Conditions
- Heart Transplantation
- Keywords
- Marrow/hematopoietic stem cell transplant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Suzanne T. IldstadUniversity, hospital or other
- Study start
- Jul 2003
- Primary completion
- 7 Nov 2011 (actual)
- Study completion
- 1 Dec 2016 (actual)
- 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 who need a heart transplant.
Detailed description
At the present time, heart transplant recipients must take anti-rejection medication to prevent rejection of the donated heart. 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 heart 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 heart 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 heart 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 heart 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 heart transplantation. Our goal is to evaluate the potential of safely establishing mixed chimerism to induce tolerance following heart 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
- Model description
- Open label
| Arm | Type | Receives |
|---|---|---|
| Cardiac Failure Patients | Experimental | Biological: enriched hematopoetic stem cell infusionRecipients treated with an enriched hematopoetic stem cell infusion from the heart donor's bone marrow |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Subject must be between the ages of 18 and 70 years and meet the institution's criteria for cardiac transplantation.
- Subjects must have acceptable negative results for infectious disease markers done within two weeks of the bone marrow infusion.
- Subject is receiving a first cardiac transplant.
- Subjects receiving a multi-organ transplant (i.e., heart/kidney) may be included at the discretion of the PI and investigators.
- Note: These multi-organ subjects will have identical criteria with the exception of adequate function of the affected organ to be transplanted (i.e., kidney). They are included in the total of thirty subjects to be transplanted.
Key exclusion criteria (5 listed)
- Clinically active bacterial, fungal, viral or parasitic infection
- Pregnancy
- Previous radiation therapy at a dose that would preclude TBI
- Subject is unable to give informed consent
- If the procedures associated with the study (i.e., delivering TBI) would significantly extend the cold ischemia time of the heart, the protocol will be abandoned and the patient will receive a conventional heart transplant.
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 hematopoetic stem cell infusionEnriched Hematopoetic Stem Cell Infusion | Biological | Cardiac Failure Patients |
Primary outcome
Enriched Hematopoetic Stem Cell Engraftment
Time frame: One month to three years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2020.
- 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.
Suzanne T Ildstad, MD study director
University of Louisville
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing enriched hematopoetic stem cell infusion in people with Heart Transplantation, run by Suzanne T. Ildstad.
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 9 inclusion and 5 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 31 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Enriched Hematopoetic 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?
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 31 Aug 2020.