Immune Tolerance
Conditions
Brief summary
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.
Detailed description
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 Subjects will be withdrawn from the immunosuppression if they have met the withdrawal criteria.
Interventions
BIOLOGICALCombined Deceased Donor Kidney and Hematopoietic Cell Transplants
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.
Sponsors
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
RECIPIENT INCLUSION CRITERIA: 1. Patient is ≥ 18 years old, and \<65 years of age. 2. Has End Stage Renal Disease (ESRD) and is a de novo kidney transplant candidate part Stanford standard of care. 3. Listed with the Organ Procurement and Transplantation Network (OPTN) for deceased donor transplantation. 4. A serotypic (Human Leucocyte Antigen) HLA match with the donor of a least 1 locus in A, B or DR. 5. Males and females of reproductive potential who agree to practice a reliable form of contraception for at least 1 year post transplant. 6. Females have a negative serum pregnancy test. 7. Ability to understand and the willingness to sign a written informed consent document. Patients must have signed informed consent to participate in the trial. 8. No known contraindication to administration of rabbit ATG or low dose irradiation. DONOR INCLUSION CRITERIA: 1. Brain dead donor aged ≥ 16 and ≤ 55 2. Organ Procurement Organization (OPO) consent for vertebral body procurement 3. Organ Procurement Organization consent for research 4. Projected cold ischemia time \<24 hours.
Exclusion criteria
RECIPIENT
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine the dose of TBI that will support donor CD3 Tcell chimerism between 30-75% at 45 days post infusion | day 45 | TBI dose in cGy associated with donor Tcell chimerism of \>30 % immunosuppressive drug monotherapy. |
| Number of patients out of the total patients enrolled who received both the kidney and the bone marrow from the same donor. | 6 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Persistence of donor chimerism >1% | 3,6,9,12,15,18,24,48,60 months | Percentage of patients with donor chimerism (any lineage) |
| Number of patients with either bacterial, viral or fungal infection within 12 months post transplant . | 12 months | — |
| Serum Creatinine | up to 60 months | — |
| Panel-Reactive Antibody (PRA) | Baseline, month 9, and month 12 | Report % of PRA on all participants |
| Donor-Specific Antibody (DSA) | Baseline, month 9, and month 12 | Report percentage of patients that develop DSA |
| Number of patients who develop GVHD, all grades and types, within 60 months of kidney transplant | 60 months | — |
| Percentage of subjects on immunosuppressive medications after an eighteen month post transplant till month 60. | 60 months | — |
Countries
United States
Contacts
CONTACTCarlos Lazarte, B.A.
CONTACTAnika Tahsin, BS
PRINCIPAL_INVESTIGATORRobert Lowsky, MD
Stanford University
PRINCIPAL_INVESTIGATORStephan Busque, MD
Stanford University
Outcome results
None listed