Kidney and Blood Stem Cell Transplantation That Eliminates Requirement for Immunosuppressive Drugs

NCT00319657 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 367P01HL075462-02
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The Stanford Medical Center Program in Multi-Organ Transplantation and the Division of Bone Marrow Transplantation are enrolling patients into a research study to determine if blood stem cells injected after kidney transplantation, in combination with lymphoid irradiation ,will change the immune system such that immunosuppressive drugs can be completely withdrawn. Patients must have a healthy, completely human leukocyte antigen (HLA)-matched brother or sister as the organ and stem cell donor. One to two months before kidney transplant surgery, blood stem cells will be removed from the donor and the cells will be frozen. After transplant surgery, the recipient will receive radiation and anti-T cell antibody treatments for two weeks to prepare for injection of the stem cells. The stem cells will be injected at the end of the two-week treatment. If the stem cells persist in the recipient, immunosuppressive drugs will be gradually reduced until they are withdrawn completely at least six months after transplantation. Patients will be followed in the Stanford clinics for transplant patients. Patients who live outside of the San Francisco Bay Area must remain near Stanford for six weeks after transplant surgery.

Conditions

Immune Tolerance

Keywords

Kidney Transplantation; Blood Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Discontinuation of maintenance immunosuppressive drugs

  Study subjects are discontinued from immunosuppressive drugs as they have achieved immune tolerance at 12 months

  Measured at 12 months

Study Arms (1)

Immune tolerance, kidney transplantation

EXPERIMENTAL

Intervention: Participants will receive hematopoietic cell transplantation and Total lymphoid irradiation. The intervention is intended to induce immune tolerance in HLA-matched living donor kidney transplantation, 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 the 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 - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Kidney transplant performed at Stanford University Medical Center
• Have an HLA-matched sibling donor
• No known contraindication to administration of rabbit ATG or radiation
• Willing to use a reliable form of contraception for at least 24 months following transplantation

You may not qualify if:

• Previous treatment with rabbit ATG or a known allergy to rabbit proteins
• History of cancer, other than non-melanoma skin cancer
• Pregnant or breastfeeding
• HIV, Hepatitis B, or Hepatitis C infection
• Previous organ transplant
• Leukopenia (white blood cell count less than 3000/mm³)
• Thrombocytopenia (platelet count less than 100,000/mm³)
• cPRA\>80%

Sponsors & Collaborators

• Stanford University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Stanford University, School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (5)

• Strober S, Benike C, Krishnaswamy S, Engleman EG, Grumet FC. Clinical transplantation tolerance twelve years after prospective withdrawal of immunosuppressive drugs: studies of chimerism and anti-donor reactivity. Transplantation. 2000 Apr 27;69(8):1549-54. doi: 10.1097/00007890-200004270-00005.

  PMID: 10836360 BACKGROUND

• Millan MT, Shizuru JA, Hoffmann P, Dejbakhsh-Jones S, Scandling JD, Grumet FC, Tan JC, Salvatierra O, Hoppe RT, Strober S. Mixed chimerism and immunosuppressive drug withdrawal after HLA-mismatched kidney and hematopoietic progenitor transplantation. Transplantation. 2002 May 15;73(9):1386-91. doi: 10.1097/00007890-200205150-00005.

  PMID: 12023614 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 RESULT

• 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 RESULT

• Jensen KP, Hongo DA, Ji X, Zheng P, Pawar R, Wu TH, Busque S, Scandling JD, Shizuru JA, Lowsky R, Shori A, Dutt S, Waters J, Saraswathula A, Baker J, Tamaresis JS, Lavori P, Negrin R, Maecker H, Engleman EG, Meyer E, Strober S. Development of immunosuppressive myeloid cells to induce tolerance in solid organ and hematopoietic cell transplant recipients. Blood Adv. 2021 Sep 14;5(17):3290-3302. doi: 10.1182/bloodadvances.2020003669.

  PMID: 34432869 DERIVED

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 Strober, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair of Study

Model Details: Combined hematopoietic stem cell and kidney transplantation

Study Record Dates

• First Submitted: April 28, 2006
• First Posted: April 27, 2006
• Study Start: July 1, 2004
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: June 18, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)