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Trial record 2 of 2 for:    david sachs

Combined Kidney and Bone Marrow Transplantation to Prevent Kidney Transplant Rejection

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ClinicalTrials.gov Identifier: NCT00801632
Recruitment Status : Completed
First Posted : December 3, 2008
Results First Posted : May 12, 2015
Last Update Posted : November 10, 2015
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE December 2, 2008
First Posted Date  ICMJE December 3, 2008
Results First Submitted Date  ICMJE April 21, 2015
Results First Posted Date  ICMJE May 12, 2015
Last Update Posted Date November 10, 2015
Study Start Date  ICMJE December 2008
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 21, 2015)
Number of Participants Successfully Withdrawn Off of Immunosuppressant Medication for 104 Weeks [ Time Frame: 48 months post-transplant ]
A participant was considered a success if they were off immunosuppressive therapy for 104 consecutive weeks leading up to study week 208 (48 months post-transplant) or study termination, whichever occurred first.
Original Primary Outcome Measures  ICMJE
 (submitted: December 2, 2008)
Successful and complete withdrawal of immunosuppressive medications for 24 consecutive months [ Time Frame: 48 months post-transplant ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2015)
  • Percentage of Participants Experiencing Acute Rejection [ Time Frame: Transplantation until study completion or participant termination (up to five years) ]
    The percentage of participants who experience an acute rejection. Acute rejection is defined as a biopsy with findings of Banff score of grade IA or higher. The Banff classification is as follows: grade IA is >25% of parenchyma affected and foci of moderate tubulitis; Grade IB is >25% of parenchyma affected and foci of severe tubulitis; Grade IIA is mild to moderate intimal arteritis; Grade IIB is severe intimal arteritis comprising >25% of the luminal area; Grade III is "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation.
  • Change in Renal Function [ Time Frame: Transplantation until study completion or participant termination (up to five years) ]
    Change in renal function as seen in serum creatinine values from baseline until study completion or participant termination. Baseline is defined as the lowest serum creatinine collected during stabilization period or in the four weeks following the end of the stabilization period. The stabilization period is defined as four consecutive creatinine values close in value (not differing more than 0.3 mg/dL). Higher results indicate poorer kidney function, as creatinine is removed from the body by the kidneys.
  • Percentage of Participants With Graft Survival Through 156 Weeks [ Time Frame: Transplantation until week 156 ]
    The percentage of participants with graft survival from transplantation through 156 weeks. Participants who terminated from the study prior to Week 156 without meeting the event were excluded. Graft survival is defined as the time to week 156 or graft loss. Graft loss is defined as the day on which a graft is deemed irreversibly nonfunctional and dialysis is begun, a transplantectomy is performed, or the participant is re-transplanted, whichever comes first. Six consecutive weeks of dialysis are required for the diagnosis of graft loss, though the date of graft loss will be defined as the date of first dialysis.
  • Percentage of Participants Surviving Through 156 Weeks [ Time Frame: Transplantation until week 156 ]
    The percentage of participants who survived from transplantation through 156 weeks. Participants who terminated from the study prior to Week 156 without meeting the event were excluded.
  • Time to Neutrophil Recovery Following Transplant [ Time Frame: Transplantation until study completion or participant termination (participants followed up to five years) ]
    Time (in days) until neutrophil recovery following transplant. Neutrophil recovery is defined as an absolute neutrophil count (ANC) > 500/mm^3 at three consecutive assessments on different days post-transplant. Time to recovery is time from transplantation until the first assessment date used to confirm the recovery.
  • Time to Platelet Recovery Following Transplant [ Time Frame: Transplantation until study completion or participant termination (participants followed up to five years) ]
    Time (in days) until platelet recovery following transplant. Platelet recovery is defined as a platelet count >20,000 /mm^3 and where no transfusion is required. Time to recovery is time from transplantation until platelet value recovers.
  • Percentage of Participants Experiencing a Clinically Significant Invasive or Resistant Opportunistic Infection [ Time Frame: Transplantation until study completion or participant termination (participants followed up to five years) ]
    Clinically significant invasive or resistant opportunistic infections include cytomegalovirus, herpes zoster, and candida.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 2, 2008)
  • Acute and chronic rejection-free survival [ Time Frame: assessed from time of transplant ]
  • Renal function [ Time Frame: Assessed from time of transplant ]
  • Participant and graft survival [ Time Frame: Assessed from time of transplant ]
  • Time to neutrophil recovery following transplant [ Time Frame: Assessed from time of transplant ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combined Kidney and Bone Marrow Transplantation to Prevent Kidney Transplant Rejection
Official Title  ICMJE Renal Allograft Tolerance Through Mixed Chimerism
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Kidney Transplantation
  • Kidney Failure, Chronic
Intervention  ICMJE
  • Procedure: Kidney Transplantation
    Surgical transplantation of donor kidney
    Other Name: Renal Transplantation
  • Procedure: Bone marrow transplantation
    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 Names:
    • siplizumab
    • anti-CD2 monoclonal antibody
  • Drug: cyclophosphamide
    60 mg/kg infusion on days -5, -4
    Other Name: Cytoxan
  • Biological: rituximab
    375 mg/m^2 infusion on days -7, -2, 5, and 12
    Other Name: Rituxan
  • Drug: Tacrolimus
    0.05 mg/kg intravenously twice daily 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®
  • 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 Names:
    • methylprednisolone
    • prednisone
  • Radiation: thymic irradiation
    700 cGy of thymic irradiation administered in a single dose on day -1
Study Arms  ICMJE Experimental: Kidney and Marrow Recipients
Combined kidney and bone marrow transplant
Interventions:
  • Procedure: Kidney Transplantation
  • Procedure: Bone marrow transplantation
  • Biological: MEDI-507
  • Drug: cyclophosphamide
  • Biological: rituximab
  • Drug: Tacrolimus
  • Drug: corticosteroids
  • Radiation: thymic irradiation
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 10, 2014)
5
Original Estimated Enrollment  ICMJE
 (submitted: December 2, 2008)
15
Actual Study Completion Date  ICMJE November 2014
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 Epstein-Barr virus (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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00801632
Other Study ID Numbers  ICMJE DAIT ITN036ST
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Immune Tolerance Network (ITN)
Investigators  ICMJE
Principal Investigator: David Sachs, MD Massacusetts General Hospital
Principal Investigator: Ben Cosimi, MD Massachusetts General Hospital
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date November 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP