Immune Tolerance Clinical Trial
Official title:
Phase I Study of Combined Deceased Donor Kidney and Hematopoietic Cell Transplants Using a Regimen to Promote Hematopoietic Cell Engraftment
Verified date | May 2022 |
Source | Stanford University |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Enrolling by invitation |
Enrollment | 30 |
Est. completion date | October 1, 2029 |
Est. primary completion date | October 1, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility | 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 EXCLUSION CRITERIA: 1. Known allergy to rabbit protein. 2. History of malignancy with the exception of non melanoma skin malignancy. 3. Pregnant woman or nursing mother. 4. Body weight >90kg or BMI >35. 5. Evidence of HIV 1/2 antibody (Ab), HTLV 1 and HTLV 2 Ab (Human T-Lymphotropic Virus), Hepatitis B sAg (surface antigen), Hepatitis C Ab, or positive syphilis screen. 6. EBV (Epstein Bar Virus)Ab positive donor to EBV Ab negative recipient. 7. Active bacterial, viral or fungal infection defined as currently taking medication for the infection. 8. Leukopenia (white blood cell count < 3000/mm3) or thrombocytopenia (with a platelet count < 100,000/mm3). 9. Psychiatric disorder(s) or psychosocial circumstance(s) which in the opinion of the Stanford Transplant team caring for this potential patient would place the patient at an unacceptable risk. 10. Concern for alcohol or other substance abuse. 11. Kidney disease at high risk for post transplant recurrence: aHUS (atypical hemolytic- uremic syndrome) and C3 glomerulopathy 12. Panel reactive antibody (PRA) >80%. 13. Positive donor specific antibody (DSA). 14. Prior or combined organ transplant. 15. Patients with >5 pack year smoking history, smoking within 10 years of enrollment, or first degree relative with lung cancer. DONOR EXCLUSION CRITERIA: 1. History of malignancy with the exception of non melanoma skin malignancy. 2. History of autoimmune disease. 3. Known medical diagnosis of Zika virus infection within the prior 6 months, including post mortem screening. 4. Serological evidence of HIV, Hepatitis B (surface antigen positive), or Hepatitis C infection. 5. Evidence of systemic infection. 6. Kidney Donor Profile Index (KDPI) > 70%. |
Country | Name | City | State |
---|---|---|---|
United States | Stanford University | Palo Alto | California |
Lead Sponsor | Collaborator |
---|---|
Stanford University |
United States,
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). pii: eaax8863. doi: 10.1126/scitranslmed.aax8863. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of patients out of the total patients enrolled who received both the kidney and the bone marrow from the same donor. | 6 months | ||
Primary | 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 | |
Secondary | Number of patients who develop GVHD, all grades and types, within 60 months of kidney transplant | 60 months | ||
Secondary | Number of patients with either bacterial, viral or fungal infection within 12 months post transplant . | 12 months | ||
Secondary | Serum Creatinine | up to 60 months | ||
Secondary | Panel-Reactive Antibody (PRA) | Report % of PRA on all participants | Baseline, month 9, and month 12 | |
Secondary | Donor-Specific Antibody (DSA) | Report percentage of patients that develop DSA | Baseline, month 9, and month 12 | |
Secondary | Percentage of subjects on immunosuppressive medications after an eighteen month post transplant till month 60. | 60 months | ||
Secondary | Persistence of donor chimerism >1% | Percentage of patients with donor chimerism (any lineage) | 3,6,9,12,15,18,24,48,60 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT04621916 -
Preventing Inhibitor Recurrence Indefinitely
|
Phase 4 | |
Recruiting |
NCT06243289 -
Improving KIdney Transplantation With Cellular Therapy Study
|
||
Recruiting |
NCT03591302 -
Delayed Blood Stem Transplantation in HLA Matched Kidney Transplant Recipients to Eliminate Immunosuppressive Drugs.
|
Phase 1 | |
Completed |
NCT04525456 -
Immune Responses With Reduxium
|
N/A | |
Recruiting |
NCT04314518 -
The Correlation Between Immunological Reaction of the Seminal Fluid in the Mother's Blood and Pregnancy Complications
|
||
Recruiting |
NCT01367821 -
Immune Function in Patients With Obstructive Jaundice
|
N/A | |
Enrolling by invitation |
NCT01117077 -
The Immune Tolerance Mechanism Induced by IL-17-producing Regulatory T Cells in the Orthotopic Liver Transplant Recipients With Aspergillosis
|
N/A | |
Terminated |
NCT05010174 -
Long-term Safety Follow-up in Recipients Who Previously Received Medeor's Cellular Immunotherapy Products
|
||
Active, not recruiting |
NCT03744325 -
Immune Responses in Hen's Egg Oral Immunotherapy
|
N/A | |
Completed |
NCT03383211 -
Immune Response to BCG Vaccination in Neonates Born to HIV and LTBI Infected and Non-infected Mothers
|
||
Recruiting |
NCT02861872 -
Intra-peritoneal Chemotherapy in Ovarian Cancer
|
N/A | |
Active, not recruiting |
NCT00319657 -
Kidney and Blood Stem Cell Transplantation That Eliminates Requirement for Immunosuppressive Drugs
|
Phase 1/Phase 2 | |
Completed |
NCT01538485 -
Vitamin D Supplementation and Regulatory FoxP3+ T Cells in the GUT
|
Phase 4 | |
Completed |
NCT03393793 -
HEart trAnsplantation Registry of piTie-Salpetriere University Hospital
|
||
Completed |
NCT01996774 -
Immunologic Profile of Children With Severe Allergies to Peanuts and Nuts After Induction of Tolerance
|
N/A | |
Recruiting |
NCT03292445 -
Inducing Graft Tolerance in HLA Haplotype Matched Related and 3 Ag Matched Unrelated Living Donor Kidney Transplantation
|
Early Phase 1 | |
Active, not recruiting |
NCT05745792 -
Clinico-immunological Characterization and Immune Tolerance Breakdown in HU-autoimmunity
|
||
Completed |
NCT02642237 -
The Effects of Preceding LPS Administration on the Fluenz-induced Immune Response
|
N/A | |
Completed |
NCT01414504 -
Pneumococcal Conjugate Vaccine Followup
|
Phase 2 | |
Not yet recruiting |
NCT06147375 -
Efficacy and Safety of Immunosuppressive Withdrawal After Pediatric Liver Transplantation
|
N/A |