Delayed Blood Stem Transplantation in HLA Matched Kidney Transplant Recipients to Eliminate Immunosuppressive Drugs.

NCT03591302 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: 46787
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The study will determine whether patients with functioning Human Leukocyte Antigen (HLA) matched kidney transplants for at least one year and who want to discontinue immunosuppressive drugs can be treated with Total Lymphoid Irradiation (TLI) and rabbit Anti-Thymocyte Globulin (rATG) and an HLA matched donor hematopoietic progenitor cell infusion such that their drugs are successfully withdrawn while maintaining normal renal function.

Conditions

Immune Tolerance

Keywords

Kidney Transplantation; Blood Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Percentage of patients no longer dependent on immunosuppressive drugs to maintain normal renal function.

  A patient will be considered no longer dependent if able to maintain normal renal function after coming off immunosuppressive medications.

  six months to up to five years post stem cell transplant

Secondary Outcomes (2)

• Percentage of patients experiencing biopsy proven rejection episodes requiring treatment requiring corticosteroids.

  One year to five years

• Percentage of patients experiencing graft loss.

  One year to five years

Study Arms (1)

Immune tolerance, Kidney transplantation

EXPERIMENTAL

Intervention: HLA matched living donor recipients of a functioning kidney transplant graft at one year will receive hematopoietic cell transplantation and Total lymphoid irradiation. The intervention is intended to induce immune tolerance such as to allow withdrawal of the immunosuppressive drugs. Immune tolerance is achieved through the development of donor/recipient mixed chimerism following combined kidney and hematopoietic stem cell transplantation from the living donor.

Biological: Hematopoietic cell transplantation; Radiation: Total Lymphoid irradiation

Interventions

Hematopoietic cell transplantation BIOLOGICAL

Transplantation of hematopoietic stem cells from living donor.

Immune tolerance, Kidney transplantation

Total Lymphoid irradiation RADIATION

Total lymphoid irradiation is used as part of the conditioning regimen for the hematopoietic stem cell transplant.

Immune tolerance, Kidney transplantation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All consenting adults of age 18 years and older with previous HLA matched sibling living donor renal transplants who still have their HLA- matched kidney donor available, and who have no history of acute or chronic rejection.
• Patients who agree to participate in the study and sign an Informed Consent
• The HLA-matched donor meets the Stanford Bone Marrow Transplant criteria for stem cell donation, agrees to participate and has signed an Informed Consent.
• The pair is confirmed to be HLA-matched (2 haplo type match) as determined by the histocompatibility laboratory at Stanford.
• Patients who have no known contraindication to the administration of rabbit ATG or radiation
• Males and females of reproductive potential who agree to practice a reliable form of contraception for at least 18 months post transplant.

You may not qualify if:

• Known allergy to ATG or a known allergy to rabbit proteins.
• History of malignancy with the exception of non-melanoma skin malignancies.
• Pregnant women or nursing mothers.
• Serological evidence of HIV, Hepatitis B (HepBsAg+) or Hepatitis C infection.
• Leukopenia (with a white blood cell count \< 3000/mm3) or thrombocytopenia (platelet count \< 100,000/mm3)
• Previous history of acute or chronic rejection of the kidney transplant or recurrence of the original disease.
• Screening kidney biopsy demonstrating acute or chronic rejection, recurrence of original disease or interstitial fibrosis/Tubular Atrophy (IF/TA) score greater than 1.

Sponsors & Collaborators

• Stephan Busque: lead

Study Sites (1)

Stanford University Medical Center

Palo Alto, California, 94304, United States

RECRUITING

Related Publications (5)

• Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Millan MT, Shizuru JA, Hoppe RT, Lowsky R, Engleman EG, Strober S. Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med. 2008 Jan 24;358(4):362-8. doi: 10.1056/NEJMoa074191.

  PMID: 18216356 BACKGROUND

• Scandling JD, Busque S, Shizuru JA, Engleman EG, Strober S. Induced immune tolerance for kidney transplantation. N Engl J Med. 2011 Oct 6;365(14):1359-60. doi: 10.1056/NEJMc1107841. No abstract available.

  PMID: 21991976 BACKGROUND

• Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Sarwal M, Millan MT, Shizuru JA, Lowsky R, Engleman EG, Strober S. Tolerance and withdrawal of immunosuppressive drugs in patients given kidney and hematopoietic cell transplants. Am J Transplant. 2012 May;12(5):1133-45. doi: 10.1111/j.1600-6143.2012.03992.x. Epub 2012 Mar 8.

  PMID: 22405058 BACKGROUND

• Scandling JD, Busque S, Shizuru JA, Lowsky R, Hoppe R, Dejbakhsh-Jones S, Jensen K, Shori A, Strober JA, Lavori P, Turnbull BB, Engleman EG, Strober S. Chimerism, graft survival, and withdrawal of immunosuppressive drugs in HLA matched and mismatched patients after living donor kidney and hematopoietic cell transplantation. Am J Transplant. 2015 Mar;15(3):695-704. doi: 10.1111/ajt.13091.

  PMID: 25693475 BACKGROUND

• Scandling JD, Busque S, Lowsky R, Shizuru J, Shori A, Engleman E, Jensen K, Strober S. Macrochimerism and clinical transplant tolerance. Hum Immunol. 2018 May;79(5):266-271. doi: 10.1016/j.humimm.2018.01.002. Epub 2018 Jan 9.

  PMID: 29330112 BACKGROUND

MeSH Terms

Interventions

Stem Cell Transplantation

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Samuel Md Strober, MD

  Stanford University

  STUDY CHAIR

Central Study Contacts

STEPHAN BUSQUE, MD

CONTACT

6504986189; sbusque@stanford.edu

Stephan Busque, MD,MS

CONTACT

6504986189; sbusque@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor for Surgery

Model Details: Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+ and T Cell Transfusion in previous HLA Matched Living Donor Kidney Transplantation

Study Record Dates

• First Submitted: June 18, 2018
• First Posted: July 19, 2018
• Study Start: September 13, 2018
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: May 10, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)