Combined Kidney and Bone Marrow Transplantation to Prevent Kidney Transplant Rejection
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.
Kidney Failure, Chronic
Procedure: Kidney Transplant
Procedure: Bone marrow transplant
Radiation: Radiation to the thymus gland
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Renal Allograft Tolerance Through Mixed Chimerism|
- Successful and complete withdrawal of immunosuppressive medications for 24 consecutive months [ Time Frame: 48-months post-transplant ] [ Designated as safety issue: No ]
- 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 ]
|Study Start Date:||December 2008|
|Estimated Study Completion Date:||August 2014|
|Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Experimental: Kidney and Marrow Recipients
Combined kidney and bone marrow transplant
Procedure: Kidney Transplant
Surgical transplantation of donor kidneyProcedure: 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 collarboneBiological: MEDI-507
0.1 mg/kg on day -2; 0.6 mg/kg on days -1,0,1
Other Name: siplizumabDrug: Cyclophosphamide
60 mg/kg infusion on days -5, -4
Other Name: Cytoxan, CTXBiological: Rituximab
375 mg/m2 infusion on days -7, -2, 5, and 12
Other Name: RituxanDrug: 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
Other Name: Prograf, FK506Drug: 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
Other Name: Prednisone, methylprednisoloneRadiation: Radiation to the thymus gland
700 cGy of thymic irradiation are administered in a single dose on day -1
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 prepares 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, plus a checkup at 2 ½, 3, 3 ½ , 4, and 5 years after transplant. 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00801632
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||David Sachs, MD||Massacusetts General Hospital|
|Principal Investigator:||Ben Cosimi, MD||Massachusetts General Hospital|