Clinical Trial: Reducing the Risk of Transplant Rejection: Simultaneous Kidney and Bone Marrow Transplant

This study has been suspended.

Sponsors and Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Immune Tolerance Network
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)

Purpose

This study will examine the safety and effectiveness of a combination kidney and bone marrow transplant from a relative with the same (or nearly the same) blood cell type as the transplant recipient. An investigational medication will be given prior to and after the transplant to help protect the transplanted kidney from attack by the body’s immune system.

Study hypothesis: The duration and level of mixed chimerism obtained using the T cell depleting antibody MEDI-507 is sufficient to induce donor-specific unresponsiveness to renal transplants in the absence of ongoing immunosuppression.

Condition Treatment or Intervention Phase
Kidney Failure
Bone Marrow Transplantation
Kidney Transplantation
Kidney Failure, Chronic
 Drug: MEDI-507
 Procedure: Combined kidney and bone marrow transplant
 Drug: Cyclosporine A
 Drug: Rituximab
 Drug: Corticosteroids
Phase I

MedlinePlus related topics:  Kidney Failure

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Official Title: Renal Allograft Tolerance Through Mixed Chimerism

Further Study Details: 
Primary Outcomes: Renal allograft acceptance; ability to discontinue immunosuppressive therapy
Secondary Outcomes: Donor-specific tolerance and chimerism; immune reconstitution; safety profile of the conditioning regimen
Expected Total Enrollment:  10

Study start: June 2003

Of the two currently available treatments for kidney failure, long-term dialysis and kidney transplantation, only kidney transplantation provides a potential cure. After a kidney transplant, the body's immune system recognizes the kidney as foreign and tries to attack and destroy it in a process called rejection. To avoid rejection, patients must take medications called immunosuppressants or anti-rejection drugs. It is believed that by transplanting bone marrow at the same time as a solid organ such as a kidney, a state of "mixed chimerism" -- a mixing of the donor and recipient's immune system -- can be achieved. Mixed chimerism may prevent rejection without the need for anti-rejection drugs.

Patients in this study will receive a simultaneous bone marrow and kidney transplant from the same living related donor in an attempt to establish mixed chimerism. Prior to transplantation, patients will undergo a "conditioning regimen" involving cyclophosphamide chemotherapy, radiation to the thymus gland, and four immunosuppressive medications: cyclosporine A, an antibody known as rituximab to suppress B cells, a short course of steroids, and a T cell depleting antibody known as MEDI-507. MEDI-507 is an investigational medication that has not been approved by the FDA. The primary goal of the study is to investigate the safety of the conditioning regimen and its ability to promote mixed chimerism so that the transplanted kidney is not destroyed. The study will also determine whether patients with mixed chimerism can eventually be safely removed from long-term immunosuppressive therapy following transplantation.

Patients will be assessed before and after transplantation and will be actively followed for 24 months. Patients will be monitored for graft rejection and medication toxicity. After Month 24, the study will continue with an additional 36 months of medical record-based surveillance.

Eligibility

Ages Eligible for Study:  18 Years   -   55 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

  • End-stage renal disease (ESRD) without prior sensitization (defined as Panel Reactive Antibody [PRA] > 20%) within the 60 days prior to transplant as measured by cytotoxicity assays, ELISA and flow cytometry
  • Undergoing a first or second transplant
  • Receiving a transplant from a living related donor who is ABO (blood type) compatible and haploidentical (3, 4, or 5 antigen match by serologic typing)
  • Negative donor lymphocyte cross-match
  • Seronegative for HIV-1, hepatitis B surface antigen (HbsAg), and hepatitis C virus
  • Cardiac ejection fraction > 40%
  • Forced expiratory volume (FEV1) > 50%
  • Liver function tests, bilirubin, and coagulation studies < 2 X normal
  • White blood cells > 2000/mm3
  • Platelets > 100,000/mm3

Exclusion Criteria:


Location Information


Massachusetts
      Massachusetts General Hospital, Boston,  Massachusetts,  02114,  United States

Study chairs or principal investigators

David H. Sachs, MD,  Principal Investigator,  Department of Medicine, Massachusetts General Hospital   
A. Benedict Cosimi, MD,  Principal Investigator,  Department of Medicine, Massachusetts General Hospital   

More Information

Click here for the Immune Tolerance Network Web site

Study ID Numbers:  ITN010ST; DAIT NKD03
Record last reviewed:  January 2005
Last Updated:  March 9, 2005
Record first received:  July 7, 2003
ClinicalTrials.gov Identifier:  NCT00063817
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

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