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

This study has been completed.
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00063817
First received: July 7, 2003
Last updated: January 27, 2012
Last verified: January 2012
  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.


Condition 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 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Renal Allograft Tolerance Through Mixed Chimerism (ITN010ST)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Renal allograft acceptance [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Ability to discontinue immunosuppressive therapy [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Donor-specific tolerance and chimerism [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Immune reconstitution [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Safety profile of the conditioning regimen [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 5
Study Start Date: June 2003
Study Completion Date: July 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Conditioning regimen consisting of cyclosporine A, rituximab, a short course of corticosteroids, and MEDI-507, followed by bone marrow and kidney transplantation occurring at the same time
Drug: MEDI-507
T-cell depleting antibody
Procedure: Combined kidney and bone marrow transplant
kidney and bone marrow transplant from same donor
Drug: Cyclosporine A
Immunosuppressant
Drug: Rituximab
B-cell suppressor
Drug: Corticosteroids
Immunosuppressant

Detailed Description:

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, a man-made 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 to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • End-stage renal disease (ESRD) without prior sensitization (defined as Panel Reactive Antibody [PRA] greater than 0%) 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)
  • Cardiac ejection fraction greater than 40%
  • Forced expiratory volume (FEV1) greater than 50%
  • Liver function tests, bilirubin, and coagulation studies less than 2 X normal
  • White blood cells greater than 2000/mm3
  • Platelets greater than 100,000/mm3

Exclusion Criteria:

  • Positive donor lymphocyte cross-match
  • HIV-1 infected
  • Positive hepatitis B surface antigen (HbsAg)
  • Hepatitis C virus infected
  • History of cancer
  • Prior dose-limiting radiation therapy
  • Pregnant, breastfeeding, or planning pregnancy within the time frame of the study
  • Enrolled in another investigational drug study within 30 days prior to study entry
  • Receiving maintenance immunosuppression within 3 months before the conditioning regimen begins
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00063817

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Immune Tolerance Network (ITN)
Investigators
Principal Investigator: David H. Sachs, MD Department of Medicine, Massachusetts General Hospital
Principal Investigator: A. Benedict Cosimi, MD Department of Medicine, Massachusetts General Hospital
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00063817     History of Changes
Other Study ID Numbers: DAIT ITN010ST, DAIT NKD03
Study First Received: July 7, 2003
Last Updated: January 27, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Renal Disease
End-stage renal disease
Renal Transplant
Bone Marrow Transplant
Tolerance, Chimerism
Immune Tolerance
ESRD

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency
Renal Insufficiency, Chronic
Kidney Diseases
Urologic Diseases
Cyclosporins
Cyclosporine
Rituximab
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 15, 2014