Kidney and Blood Stem Cell Transplantation - Eliminates Immunosuppressants

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

This study is currently recruiting participants.
Verified by National Heart, Lung, and Blood Institute (NHLBI), August 2008

Sponsored by:    National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:    National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:    NCT00319657
Purpose

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injected after kidney transplantation will change the immune system such that immunosuppressive drugs can be completely withdrawn.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 If the stem cells persist in the recipient, immunosuppressive drugs will be gradually reduced until they are withdrawn completely at six months after transplantation.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.

Condition    Intervention    Phase
Kidney Transplantation
   Procedure: Kidney transplantation
   Phase I

MedlinePlus related topics:     Kidney Transplantation

U.S. FDA Resources

Study Type:     Interventional
Study Design:     Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:     Total Lymphoid Irradiation, Anti-Thymocyte Globulin and Purified Donor CD34+ and T-Cell Transfusion in HLA-Matched Living Donor Kidney Transplantation

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

* Discontinuation of maintenance immunosuppressive drugs [ Time Frame: Measured at 6 months ] [ Designated as safety issue: No ]
* Normal kidney graft function [ Time Frame: Measured in July 2009 ] [ Designated as safety issue: Yes ]
* Stable mixed chimerism [ Time Frame: Measured at 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment:     15
Study Start Date:     July 2004
Estimated Study Completion Date:     July 2009
Estimated Primary Completion Date:     July 2009 (Final data collection date for primary outcome measure)

Arms    Assigned Interventions
1: Experimental
Kidney transplantation
   Procedure: Kidney transplantation
Kidney transplantation followed by immunosuppressive drugs for 6 months

Detailed Description:

The purpose of this study is to determine the proportion of patients that can be withdrawn completely from immunosuppressive drugs while maintaining normal function of HLA-matched living related donor kidney transplants. Fifteen participants will be conditioned with total lymphoid irradiation (TLI) and rabbit anti-thymocyte globulin (ATG), and given an infusion of donor "mobilized" blood mononuclear cells prior to transplantation.

This is a single-center, open-label study in adult renal transplant patients. Fifteen patients will receive TLI, ATG, and an infusion of CD34+ selected G-CSF mobilized blood cells combined with a fixed number (1x10^6) of CD3+ T cells from the same mobilized blood cell source. Patients will receive a one-month course of mycophenolate mofetil and a six-month tapering course of cyclosporine that will be discontinued at six months. At serial timepoints (1) graft function will be monitored, (2) chimerism will be measured in recipient white blood cell subsets, (3) mixed lymphocyte response (MLR) assays of peripheral blood mononuclear cells against donor and third party cells will be performed, and (4) protocol biopsies of the graft will be obtained. An attempt will be made to discontinue cyclosporine at six months if (1) chimerism is detectable for at least 180 days after CD34+ and CD3+ cell infusion, (2) there is stable graft function without clinical rejection episodes, and (3) there is lack of histologic rejection on protocol biopsies. In the proposed study, patients will be given a target dose of 8-10x10^6 CD34+ cells/kg and 1x10^6 CD3+ cells/kg because sustained chimerism may be necessary for sustained tolerance to the graft.
Eligibility
Ages Eligible for Study:     21 Years and older
Genders Eligible for Study:     Both
Accepts Healthy Volunteers:     No

Criteria

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)
* Panel reactive antibody (PRA) level greater than 20%

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00319657

Contacts
Contact: Samuel Strober, MD     650-723-6500     glenna@stanford.edu
Contact: Euodia Jonathan, RN     650-726-0127     euodia@stanford.edu

Locations
United States, California
   Stanford University, School of Medicine        Recruiting
     Stanford, California, United States, 94305
     Principal Investigator: Samuel Strober, MD
     Sub-Investigator: Stephan Busque, MD
     Sub-Investigator: John Scandling, MD

Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

Investigators
Principal Investigator:     Samuel Strober, MD     Stanford University
More Information

Click here for more information for this study: Kidney and Blood Stem Cell Transplantation that Eliminates All Immunosuppressive Drugs This link exits the ClinicalTrials.gov site

Publications:
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(

:1549-54.

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.

Responsible Party:     Stanford University School of Medicine ( Samuel Strober, M.D., Professor of Medicine )
Study ID Numbers:     367, P01 HL075462-02
First Received:     April 28, 2006
Last Updated:     August 7, 2008
ClinicalTrials.gov Identifier:     NCT00319657
Health Authority:     United States: Food and Drug Administration

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):
Kidney Transplantation
Blood Stem Cell Transplantation

Study placed in the following topic categories:
Antilymphocyte Serum

ClinicalTrials.gov processed this record on September 23, 2008