Combined Kidney and Bone Marrow Transplantation to Prevent Kidney Transplant Rejection

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00801632
First received: December 2, 2008
Last updated: April 10, 2014
Last verified: April 2014
  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
Biological: MEDI-507
Drug: Cyclophosphamide
Biological: Rituximab
Drug: Tacrolimus
Drug: Corticosteroids
Radiation: Radiation to the thymus gland
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


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 ]

Enrollment: 5
Study Start Date: December 2008
Estimated Study Completion Date: August 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Kidney and Marrow Recipients
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
Biological: MEDI-507
0.1 mg/kg on day -2; 0.6 mg/kg on days -1,0,1
Other Name: siplizumab
Drug: Cyclophosphamide
60 mg/kg infusion on days -5, -4
Other Name: Cytoxan, CTX
Biological: Rituximab
375 mg/m2 infusion on days -7, -2, 5, and 12
Other Name: Rituxan
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
Other Name: Prograf, FK506
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
Other Name: Prednisone, methylprednisolone
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 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.

  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
  • presence of antibody against the donor
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00801632

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Immune Tolerance Network (ITN)
Investigators
Principal Investigator: David Sachs, MD Massacusetts General Hospital
Principal Investigator: Ben Cosimi, MD Massachusetts General Hospital
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00801632     History of Changes
Other Study ID Numbers: DAIT ITN036ST
Study First Received: December 2, 2008
Last Updated: April 10, 2014
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

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases
Cyclophosphamide
Methylprednisolone
Methylprednisolone acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Alkylating Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Autonomic Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists

ClinicalTrials.gov processed this record on October 20, 2014