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Clinical Trial Details — Status: Enrolling by invitation

Administrative data

NCT number NCT04571203
Other study ID # 57511
Secondary ID
Status Enrolling by invitation
Phase Phase 1
First received
Last updated
Start date May 6, 2022
Est. completion date October 1, 2029

Study information

Verified date May 2022
Source Stanford University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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 Subjects will be withdrawn from the immunosuppression if they have met the withdrawal criteria.


Recruitment information / eligibility

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%.

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
Combined 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.

Locations

Country Name City State
United States Stanford University Palo Alto California

Sponsors (1)

Lead Sponsor Collaborator
Stanford University

Country where clinical trial is conducted

United States, 

References & Publications (1)

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

Outcome

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
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