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This is a single arm phase 1 non randomized dose finding study for safety, feasibility and efficacy of deceased donor vertebral body (VB) marrow cell infusion and kidney transplantation.
Patients will undergo a standard of care deceased donor kidney transplant and thereafter the recipient will receive TLI (Total Lymphoid Irradiation)/single low dose Total Body Irradiation, ATG (Anti-Thymocyte Globulin) conditioning, followed by an infusion of whole bone marrow cells harvested from the same donor vertebral bodies. Patients will be receive standard of care doses of steroids, MMF and tacrolimus as part of their transplant immunosuppression.
Subjects will be withdrawn from the immunosuppression if they have met the withdrawal criteria.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase I Study of Combined DD Kidney and HCT Transplant | Experimental | Single arm Phase 1 non randomized dose finding study for safety, feasibility and efficacy of deceased donor vertebral body (VB) marrow cell infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Combined Deceased Donor Kidney and Hematopoietic Cell Transplants | Biological | This combined kidney and hematopoietic cell transplants with a conditioning regimen with irradiation and ATG creates an environment of immune-tolerance. This promotes hematopoietic cell engraftment. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients out of the total patients enrolled who received both the kidney and the bone marrow from the same donor. | 6 months | |
| Determine the dose of TBI that will support donor CD3 Tcell chimerism between 30-75% at 45 days post infusion | TBI dose in cGy associated with donor Tcell chimerism of >30 % immunosuppressive drug monotherapy. | day 45 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients who develop GVHD, all grades and types, within 60 months of kidney transplant | 60 months | |
| Number of patients with either bacterial, viral or fungal infection within 12 months post transplant . | 12 months |
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Inclusion Criteria:
RECIPIENT INCLUSION CRITERIA:
DONOR INCLUSION CRITERIA:
Exclusion Criteria:
RECIPIENT EXCLUSION CRITERIA:
DONOR EXCLUSION CRITERIA:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Carlos Lazarte, B.A. | Contact | 6505548610 | lazarte6@stanford.edu | |
| Anika Tahsin, BS | Contact | atahsin@stanford.edu |
| Name | Affiliation | Role |
|---|---|---|
| Robert Lowsky, MD | Stanford University | Principal Investigator |
| Stephan Busque, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University | Recruiting | Palo Alto | California | 94305 | United States | |
| MSOB |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31996467 | Background | Busque S, Scandling JD, Lowsky R, Shizuru J, Jensen K, Waters J, Wu HH, Sheehan K, Shori A, Choi O, Pham T, Fernandez Vina MA, Hoppe R, Tamaresis J, Lavori P, Engleman EG, Meyer E, Strober S. Mixed chimerism and acceptance of kidney transplants after immunosuppressive drug withdrawal. Sci Transl Med. 2020 Jan 29;12(528):eaax8863. doi: 10.1126/scitranslmed.aax8863. |
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| ID | Term |
|---|---|
| D011827 | Radiation |
| ID | Term |
|---|---|
| D055585 | Physical Phenomena |
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End Stage Renal Disease subjects will receive a deceased donor kidney and vertebral body stem cell infusion. These transplant recipients post kidney transplant will undergo conditioning by ATG, Total Lymphoid irradiation and 1 single dose of TBI. Subsequently, the vertebral body stem cell infusion will be administered.
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|
|
| Serum Creatinine | up to 60 months |
| Panel-Reactive Antibody (PRA) | Report % of PRA on all participants | Baseline, month 9, and month 12 |
| Donor-Specific Antibody (DSA) | Report percentage of patients that develop DSA | Baseline, month 9, and month 12 |
| Percentage of subjects on immunosuppressive medications after an eighteen month post transplant till month 60. | 60 months |
| Persistence of donor chimerism >1% | Percentage of patients with donor chimerism (any lineage) | 3,6,9,12,15,18,24,48,60 months |
| Recruiting |
| Stanford |
| California |
| 94305 |
| United States |
|