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Belatacept to Prevent Organ Rejection in Kidney Transplant Patients (BESTT)

This study has been terminated.
(Stopping rule-acute rejection threshold-was met based on local biopsy results)
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00346151
First received: June 27, 2006
Last updated: December 30, 2014
Last verified: December 2014
  Purpose

Belatacept is an experimental medication shown in clinical trials to have immune system suppression properties in people who have had renal (e.g., kidney) transplants. This study will determine whether a combination of anti-rejection drugs, including belatacept, can prevent the rejection of a first-time, non-human leukocyte antigen (HLA) identical renal transplant and allow patients to be safely withdrawn from anti-rejection therapy one year post-transplant.


Condition Intervention Phase
Renal Transplant
Drug: Belatacept
Drug: Sirolimus
Drug: Anti-thymocyte globulin
Drug: methylprednisolone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Safety and Efficacy of Belatacept, Antithymocyte Globulin, and Sirolimus in Recipients of Non-HLA-identical Living-donor Renal Transplants (ITN023ST)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Acute Rejection at 6-Months [ Time Frame: 6 months post-transplant ] [ Designated as safety issue: Yes ]

    Cumulative incidence of acute rejection[1] at 6 months post-transplant based on local pathology biopsy reads

    1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater[2]
    2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999


Secondary Outcome Measures:
  • Participant Survival at 12 Months Post-Transplant [ Time Frame: 12 months post-transplant ] [ Designated as safety issue: Yes ]
  • Acute Rejection at 12-Months [ Time Frame: 12 months post-transplant ] [ Designated as safety issue: Yes ]

    Incidence of acute rejection[1] at 12 months post-transplant

    1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater[2]
    2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999

  • Tolerance Induction [ Time Frame: 48 months ] [ Designated as safety issue: No ]
    Time from transplantation to initiation of sirolimus withdrawal.

  • Renal Function as Measured by Glomerular Filtration Rate (GFR) at 24 Weeks [ Time Frame: 24 weeks post-transplant ] [ Designated as safety issue: No ]

    GFR utilizing clearance of iothalamate.

    GFR is an index of level of kidney function. A higher value means better kidney function.


  • Graft Survival at 12 Months Post-transplant [ Time Frame: 12 months post-transplant ] [ Designated as safety issue: Yes ]
  • Time From Transplant to Acute Rejection [ Time Frame: Transplantation until rejection occurs (participants followed up to four years post-transplantation) ] [ Designated as safety issue: Yes ]

    Time (days) from transplant to occurrence of acute rejection[1]

    1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater[2]
    2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999

  • Proportion of Participants Requiring Antilymphocyte Therapy for Acute Rejection [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ] [ Designated as safety issue: Yes ]

    Proportion of participants who experienced acute rejection[1] requiring antilymphocyte therapy

    1. Diagnosis of acute rejection was made by renal (kidney) biopsy using the Banff 97 criteria. The Banff 97 diagnostic category for renal allograft biopsies is an international standardized histopathological classification. Acute rejection is defined by a renal biopsy demonstrating a Banff 97 classification of Grade IA or greater[2]
    2. Reference: Racusen LC, Solez K, Colvin RB et al,The Banff 97 working classification of renal allograft pathology. Kidney Int,55: 713-723, 1999

  • Proportion of Participants With Post-transplant Infections [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ] [ Designated as safety issue: Yes ]
    Proportion of participants who experienced infections post-transplant. Participants were checked for any type of opportunistic infection at all study visits post-transplantation (up to 4 years post-transplantation)

  • Proportion of Participants With Wound Complications [ Time Frame: Start of study to end of study ] [ Designated as safety issue: Yes ]
  • Proportion of Participants With Malignancies [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ] [ Designated as safety issue: Yes ]
  • Proportion of Participants With a Sirolimus Associated Adverse Event [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ] [ Designated as safety issue: Yes ]
  • Proportion of Participants With Chronic Allograft Nephropathy [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ] [ Designated as safety issue: Yes ]
  • Proportion of Participants With Delayed Graft Function [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ] [ Designated as safety issue: Yes ]
  • Proportion of Participants With Post-transplant Diabetes Mellitus [ Time Frame: Participants followed from transplantation until completion of study (up to four years post-transplantation) ] [ Designated as safety issue: Yes ]

Enrollment: 5
Study Start Date: December 2006
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Belatacept
Immunosuppressive protocol consisting of belatacept, glucocorticoids, antithymocyte globulin (ATG), and sirolimus.
Drug: Belatacept
10 mg/kg given intravenously (IV) on transplant (day 1), day 5, and at weeks 2, 4, 8 and 12, then 5 mg/kg IV every 4 weeks
Other Names:
  • LEA29Y
  • Nulojix
Drug: Sirolimus
4 mg/day (oral tablet) at transplant (day 1), then dose adjusted to maintain serum trough level of 8-12 ng/mL for at least 1 year
Other Names:
  • Rapamycin
  • Rapamune
Drug: Anti-thymocyte globulin
1.5 mg/kg given IV daily on days 1 through 4. Subjects are premedicated with glucocorticoids, acetaminophen 650 mg by mouth, and diphenhydramine 25- 50 mg by mouth prior to each dose.
Other Names:
  • ATG
  • anti-thymocyte immunoglobulin
  • Thymoglobulin®
Drug: methylprednisolone
500 mg given IV at transplant (day 1), then given 250 mg IV on day 2 and given 0.5 mg/kg IV or prednisone 0.5 mg/kg given by mouth on days 3 and 4
Other Names:
  • Medrol
  • glucocorticoid

Detailed Description:

Drugs that suppress the immune system have contributed to increased success of transplantation; however, to prevent organ rejection, transplant recipients need to take immunosuppressive drugs for the rest of their lives. These drugs make patients more susceptible to infection and certain kinds of cancer. Belatacept is an experimental medication that specifically targets immune reactions against transplanted organs and has been shown to be effective in preventing kidney transplant rejection in previous clinical trials. Both thymoglobulin, an antibody, and sirolimus, an anti-rejection drug, prevent rejection by lowering the response of the immune system to the transplanted organ. This study will evaluate whether belatacept, along with thymoglobulin and sirolimus, is safe in kidney transplant patients. The study will also evaluate this regimen's potential to allow tapering and eventual discontinuation of all immunosuppressive drugs.

This study will last up to 4 years. At the time of transplant, participants will begin an immunosuppressive treatment regimen consisting of thymoglobulin, sirolimus, and belatacept. Participants will receive infusions of thymoglobulin on days 1 through 4, and a combination of oral sirolimus (daily) and belatacept infusions at day 5, then weeks 2, 4, 8, and monthly for at least 2 years. Dose reduction of belatacept will occur at 12 weeks post-transplant. At Year 2, eligible participants may choose to begin drug withdrawal or continue study therapy through the end of the study. Study visits will occur weekly for the first two months, then monthly. These visits will include belatacept treatment, general medical assessments, blood and urine collection, and other assessments to determine overall health of the recipient's immune system and kidney transplant and to better understand the way the immune system works in the acceptance or rejection of organ transplants.

*** IMPORTANT NOTICE: *** The National Institute of Allergy and Infectious Diseases and the Immune Tolerance Network do not recommend the discontinuation of immunosuppressive therapy for recipients of cell, organ, or tissue transplants outside of physician-directed, controlled clinical studies. Discontinuation of prescribed immunosuppressive therapy can result in serious health consequences and should only be performed in certain rare circumstances, upon the recommendation and with the guidance of your health care provider.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Receiving first renal (e.g., kidney) transplant
  • Transplant is from a non-HLA-identical living donor
  • Willing to use acceptable forms of contraception

Exclusion Criteria:

  • Positive for anti-human globulin (AHG) or T-cell cross-match with the donor
  • Receiving multiple-organ transplant
  • History of cancer within the 5 years prior to study entry. Patients who have certain nonmelanoma skin cancers are not excluded
  • Human immunodeficiency virus (HIV) infected
  • Hepatitis B (HBV) or C (HCV) virus infected
  • Other active infections
  • Active tuberculosis (TB) infection within the 3 years prior to study entry
  • Pregnancy or breastfeeding
  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: NCT00346151

Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
Sponsors and Collaborators
Immune Tolerance Network (ITN)
Investigators
Principal Investigator: Flavio Vincenti, MD University of California, San Francisco
Principal Investigator: Christian Larsen, MD Emory University
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00346151     History of Changes
Other Study ID Numbers: DAIT ITN023ST
Study First Received: June 27, 2006
Results First Received: June 8, 2011
Last Updated: December 30, 2014
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 transplantation
kidney transplantation
renal allograft recipient
anti-rejection drugs
immunosuppression protocol
immunosuppression withdrawal

Additional relevant MeSH terms:
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on March 03, 2015