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Combined Kidney and Bone Marrow Transplantation to Prevent Kidney Transplant Rejection (SMART)
This study is currently recruiting participants.
Verified by National Institute of Allergy and Infectious Diseases (NIAID), December 2008
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)
ClinicalTrials.gov Identifier: NCT00801632
  Purpose

In small initial studies, combined kidney and bone marrow transplants from the same donor have permitted some individuals to stop taking anti-rejection medicines without rejecting their transplant. This clinical trial will study this method in a greater number of people to determine if it is indeed effective and safe.


Condition Intervention Phase
Kidney Transplantation
Kidney Failure, Chronic
Procedure: Kidney Transplant
Procedure: Bone marrow transplant
Drug: MEDI-507
Drug: Cyclophosphamide
Drug: Rituximab
Drug: tacrolimus
Drug: Corticosteroids
Radiation: Radiation to the thymus gland
Phase II

MedlinePlus related topics: Bone Marrow Transplantation Kidney Failure Kidney Transplantation
Drug Information available for: Cyclophosphamide Methylprednisolone Prednisone Rituximab Tacrolimus Corticosteroids Tacrolimus anhydrous Siplizumab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Efficacy Study
Official Title: Renal Allograft Tolerance Through Mixed Chimerism

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

Primary Outcome Measures:
  • Successful and complete withdrawal of immunosuppressive medications for 24 consecutive months [ Time Frame: 48-months post-transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Acute and chronic rejection-free survival [ Time Frame: assessed from time of transplant ] [ Designated as safety issue: Yes ]
  • Renal function [ Time Frame: Assessed from time of transplant ] [ Designated as safety issue: No ]
  • Participant and graft survival [ Time Frame: Assessed from time of transplant ] [ Designated as safety issue: Yes ]
  • Time to neutrophil recovery following transplant [ Time Frame: Assessed from time of transplant ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 15
Study Start Date: December 2008
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Protocol: Experimental
Combined kidney and bone marrow transplant
Procedure: Kidney Transplant
Surgical transplantation of donor kidney
Procedure: Bone marrow transplant
During kidney transplant, bone marrow cells donated by the same donor as the kidney are given through a plastic tube placed in a vein in the chest, underneath the collarbone
Drug: MEDI-507
0.1 mg/kg on day -2; 0.6 mg/kg on days -1,0,1
Drug: Cyclophosphamide
60 mg/kg infusion on days -5, -4
Drug: Rituximab
375 mg/m2 infusion on days -7, -2, 5, and 12
Drug: tacrolimus
0.05 mg/kg IV twice a day starting on day -1, adjusted to trough level of 10-15ng/ml, then tapered (if eligible) on days 1, 7, 14, 21, 28, 42, and 56
Drug: Corticosteroids
2 mg/kg prednisone on day 4, with an additional 500-mg pulse of methylprednisolone given on days 10, 11, and 12, and then tapered off by day 20
Radiation: Radiation to the thymus gland
700 cGy of thymic irradiation are administered in a single dose on day -1

Detailed Description:

All patients receiving an organ or tissue transplant must take special medicines known as "immunosuppressive drugs" in order to prevent the immune system from rejecting the transplant. These drugs can be very effective, but they leave the patient at an increased risk of serious infections and certain types of cancer. New methods of preventing transplant rejection are needed.

Researchers have found that transplanting both bone marrow and a kidney from the same donor can create what is called "mixed chimerism." This means that the transplant recipient has a mixture of the donor and recipient's immune systems. It is believed that this mixture of immune cells can prevent rejection of the kidney. In a small prior study, performing a kidney transplant together with a bone marrow transplant from the same donor allowed 4 of 5 patients to stop taking immunosuppressive drugs altogether, without rejecting their transplant. This clinical trial will study more patients to confirm if the technique is safe and effective.

Patients eligible for this study must be candidates for a living kidney transplant, and have an eligible donor identified. The transplant recipient and donor must both consent to participate in this study. Transplant recipients enrolled in the study will receive both kidney and bone marrow transplants from the same living donor. Prior to the transplant procedure, the transplant recipient will undergo a "conditioning regimen" that makes room in their immune system for the recipient's immune (bone marrow) cells. This conditioning regimen is a combination of chemotherapy, radiation, immunosuppressive drugs and specialized medications called rituximab and MEDI-507. MEDI-507 is an investigational medication that has not been approved by the FDA. After the transplant procedure, transplant recipients will be prescribed steroids for several weeks and immunosuppressive drugs. After 2 months, the dose of the immunosuppressive drugs will slowly be decreased to zero in patients whose immune system and kidney function meet certain criteria.

Transplant recipients enrolled into the study will be hospitalized for 1 week prior to the transplant procedure. After the transplant, patients will remain in the hospital until the doctor feels they are well enough to go home. Recipients will receive approximately monthly checkups over a period of 2 years after transplant and may be asked attend checkups once per year for up to 3 additional years. Checkups will include physical exams, and blood and urine tests to assess immune system and kidney function. At four of these checkups, a kidney biopsy will be requested.

Transplant donors enrolled in the study will attend a screening visit, which will include a physical exam, blood tests and chest x-ray. Eligible donors will be admitted to the hospital for 3-5 days, where bone marrow will be collected prior to removal of the kidney. Transplant donors may be asked at a later date to donate additional blood samples for research purposes.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • awaiting first or second transplant with a living donor or first transplant with a cadaveric donor
  • for living-donor transplants, must have one or more HLA antigen-mismatched donors identified
  • Serologic evidence of prior exposure to EBV

Exclusion Criteria:

  • ABO blood group-incompatibility for a kidney graft of tissue from a donor
  • Decreased circulating white blood cell count
  • positive for HIV-1, hepatitis B and C viruses
  • have had prior radiation therapy that could limit dose
  • lung capacity <50% of predicted normal
  • evidence of insufficient cardiac capacity
  • unwilling to use adequate contraception until 2 years after transplant
  • lactation or pregnancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00801632

Contacts
Contact: Sandy deBronkart, RN (617) 726-2631 sdebronkart@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Sandy deBronkart, RN     617-726-2631     sdebronkart@partners.org    
Principal Investigator: David H Sachs, MD            
United States, New York
New York-Presbyterian/Weill Cornell Medical Center Not yet recruiting
New York, New York, United States
Principal Investigator: Manikkam Suthanthiran, MD            
United States, Pennsylvania
University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States
Principal Investigator: Abraham Shaked, MD, PhD            
Sponsors and Collaborators
Immune Tolerance Network
Investigators
Principal Investigator: David Sachs, MD Massacusetts General Hospital
Principal Investigator: Ben Cosimi, MD Massachusetts General Hospital
  More Information

Immune Tolerance Network  This link exits the ClinicalTrials.gov site

Publications:
Responsible Party: DAIT/NIAID ( Associate Director, Clinical Research Program )
Study ID Numbers: ITN036ST
Study First Received: December 2, 2008
Last Updated: December 30, 2008
ClinicalTrials.gov Identifier: NCT00801632  
Health Authority: United States: Institutional Review Board;   United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
kidney
renal
transplant
transplantation
kidney transplant
rejection
antirejection
immunosuppression
tolerance
transplant tolerance
immune tolerance
mixed chimerism
bone marrow

Study placed in the following topic categories:
Prednisone
Renal Insufficiency
Rituximab
Methylprednisolone
Kidney Failure, Chronic
Methylprednisolone acetate
Prednisolone acetate
Cyclophosphamide
Tacrolimus
Urologic Diseases
Renal Insufficiency, Chronic
Prednisolone
Kidney Diseases
Kidney Failure
Methylprednisolone Hemisuccinate

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Antineoplastic Agents, Hormonal
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Gastrointestinal Agents
Antiemetics
Hormones
Glucocorticoids
Protective Agents
Neuroprotective Agents
Immunosuppressive Agents
Pharmacologic Actions
Autonomic Agents
Therapeutic Uses
Myeloablative Agonists
Peripheral Nervous System Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Central Nervous System Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009