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Belatacept in Renal Transplantation With Intermediate Risk Maryland Aggregate Pathology Index (MAPI) Scores

Primary Purpose

End-Stage Renal Disease

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Belatacept
Sponsored by
University of Maryland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for End-Stage Renal Disease focused on measuring Kidney Transplantation, Biopsy, Belatacept

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female renal recipients 18-70 years of age undergoing primary kidney transplantation.
  • Recipients of deceased donor (including expanded criteria donor organs and deceased donor organs after cardiac death) with MAPI score ≥ 8.
  • Cold ischemic time less than 40 hours at time of reperfusion.
  • Negative serum pregnancy test for female patients.
  • Patients who can understand the purposes and risks of the study, provide informed consent, and can comply with the treatment and follow-up requirements.

Exclusion Criteria:

  • Cold ischemic time (CIT) > 40 hours
  • Patients who are sensitized with current PRA>40%, ABO incompatible transplants, or T, or B cell crossmatch positive transplant.
  • Patients without antibody to EBV
  • Patients receiving multiple organ transplants.
  • Patients unable to take oral medication at time of randomization
  • Patient with a history of malignancy of any organ system, treated or untreated, within the past 2 years whether or not there is evidence of local recurrence or metastases, with the exception of carcinoma in situ
  • Patients who tested positive for HIV, Hepatitis C or Hepatitis B surface antigen.
  • Recipients of organs from donors who test positive for HIV, Hepatitis C or Hepatitis B surface antigen
  • Patients with a clinically significant systemic infection within 30 days prior to transplant
  • Patients who have cardiac failure at time of screening or any other severe cardiac disease as determined by the investigator
  • Patients with abnormal laboratory findings of clinical significance within 2 weeks of randomization which would interfere with the objectives of the study.
  • Females, pregnant or lactating, or are of childbearing potential unwilling to use an effective means of contraception or are planning to become pregnant.
  • Patient with active tuberculosis infection

Sites / Locations

  • University of Maryland

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Belatacept therapy

Arm Description

20 Patients receiving belatacept based immunosuppressive protocol for 12 months post-transplantation.

Outcomes

Primary Outcome Measures

Renal Function
To evaluate renal function in Belatacept treated recipients of intermediate risk MAPI score allografts in terms of estimated glomerular filtration rate (eGFR, calculated using the MDRD formula) assessed at 12 months. The 12 month eGFR will be compared to existing cohorts of calcineurin inhibitor treated patients with MAPI scores above 8.

Secondary Outcome Measures

Rejection rate
Secondary objectives include the biopsy proven rejection rates at 12 months and comparison to existing cohorts of calcineurin inhibitor treated patients.
Graft survival
Secondary objectives include renal allograft survival at 12 months.
MAPI biopsy score
Secondary objectives include the MAPI score at 3 and 12 months. The MAPI score change compared to baseline in the study group will be important in comparison to existing cohorts of calcineurin inhibitor treated patients, to determine whether calcineurin free-regimens are associated with both functional and histologic differences as compared to calcineurin based therapies.
Patient survival
Secondary objectives include patient survival at 12 months.

Full Information

First Posted
December 14, 2011
Last Updated
June 13, 2018
Sponsor
University of Maryland
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT01496417
Brief Title
Belatacept in Renal Transplantation With Intermediate Risk Maryland Aggregate Pathology Index (MAPI) Scores
Official Title
A 12 Month, Single-center, Non-randomized, Open-label Study of Outcomes of Intermediate Risk Maryland Aggregate Pathology Index (MAPI) Scores in de Novo Renal Transplant Recipients
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
February 28, 2017 (Actual)
Study Completion Date
March 1, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Maryland
Collaborators
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This will be a pilot study to investigate the use of belatacept (BMS) therapy in kidney transplant patients who have a MAPI score of greater than or equal to 8. The MAPI (Maryland Aggregate Pathology Index) score is a preimplantation donor scoring system which has five histopathological parameters that impact long-term kidney outcomes. Many kidney transplant recipients use calcineurin inhibitors (CNIs) as one of their anti-rejection medi cations. Kidney function may be affected by anti-rejection medications known as calcineurin inhibitors (CNIs). Sometimes CNIs can lead to toxicities and eventually loss of the kidney or episodes of chronic allograft nephropathy (CAN). Avoiding CNI immunosuppression and using belatacept therapy (BMS) instead, may be associated with improved kidney transplant outcomes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End-Stage Renal Disease
Keywords
Kidney Transplantation, Biopsy, Belatacept

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Belatacept therapy
Arm Type
Experimental
Arm Description
20 Patients receiving belatacept based immunosuppressive protocol for 12 months post-transplantation.
Intervention Type
Drug
Intervention Name(s)
Belatacept
Other Intervention Name(s)
Nulojix
Intervention Description
Belatacept infusion intravenous at 10 mg/kg on post-operative days 1, 5, and weeks 2, 4, 8, 12; 5mg/kg intravenous dose at weeks 16, 20, 24, 28, 32, 36, 40, 44, and 48.
Primary Outcome Measure Information:
Title
Renal Function
Description
To evaluate renal function in Belatacept treated recipients of intermediate risk MAPI score allografts in terms of estimated glomerular filtration rate (eGFR, calculated using the MDRD formula) assessed at 12 months. The 12 month eGFR will be compared to existing cohorts of calcineurin inhibitor treated patients with MAPI scores above 8.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Rejection rate
Description
Secondary objectives include the biopsy proven rejection rates at 12 months and comparison to existing cohorts of calcineurin inhibitor treated patients.
Time Frame
12 months
Title
Graft survival
Description
Secondary objectives include renal allograft survival at 12 months.
Time Frame
12 months
Title
MAPI biopsy score
Description
Secondary objectives include the MAPI score at 3 and 12 months. The MAPI score change compared to baseline in the study group will be important in comparison to existing cohorts of calcineurin inhibitor treated patients, to determine whether calcineurin free-regimens are associated with both functional and histologic differences as compared to calcineurin based therapies.
Time Frame
12 months
Title
Patient survival
Description
Secondary objectives include patient survival at 12 months.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female renal recipients 18-70 years of age undergoing primary kidney transplantation. Recipients of deceased donor (including expanded criteria donor organs and deceased donor organs after cardiac death) with MAPI score ≥ 8. Cold ischemic time less than 40 hours at time of reperfusion. Negative serum pregnancy test for female patients. Patients who can understand the purposes and risks of the study, provide informed consent, and can comply with the treatment and follow-up requirements. Exclusion Criteria: Cold ischemic time (CIT) > 40 hours Patients who are sensitized with current PRA>40%, ABO incompatible transplants, or T, or B cell crossmatch positive transplant. Patients without antibody to EBV Patients receiving multiple organ transplants. Patients unable to take oral medication at time of randomization Patient with a history of malignancy of any organ system, treated or untreated, within the past 2 years whether or not there is evidence of local recurrence or metastases, with the exception of carcinoma in situ Patients who tested positive for HIV, Hepatitis C or Hepatitis B surface antigen. Recipients of organs from donors who test positive for HIV, Hepatitis C or Hepatitis B surface antigen Patients with a clinically significant systemic infection within 30 days prior to transplant Patients who have cardiac failure at time of screening or any other severe cardiac disease as determined by the investigator Patients with abnormal laboratory findings of clinical significance within 2 weeks of randomization which would interfere with the objectives of the study. Females, pregnant or lactating, or are of childbearing potential unwilling to use an effective means of contraception or are planning to become pregnant. Patient with active tuberculosis infection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rolf N Barth, MD
Organizational Affiliation
University of Maryland, Baltimore
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20634298
Citation
Vincenti F, Blancho G, Durrbach A, Friend P, Grinyo J, Halloran PF, Klempnauer J, Lang P, Larsen CP, Muhlbacher F, Nashan B, Soulillou JP, Vanrenterghem Y, Wekerle T, Agarwal M, Gujrathi S, Shen J, Shi R, Townsend R, Charpentier B. Five-year safety and efficacy of belatacept in renal transplantation. J Am Soc Nephrol. 2010 Sep;21(9):1587-96. doi: 10.1681/ASN.2009111109. Epub 2010 Jul 15.
Results Reference
background
PubMed Identifier
16120857
Citation
Vincenti F, Larsen C, Durrbach A, Wekerle T, Nashan B, Blancho G, Lang P, Grinyo J, Halloran PF, Solez K, Hagerty D, Levy E, Zhou W, Natarajan K, Charpentier B; Belatacept Study Group. Costimulation blockade with belatacept in renal transplantation. N Engl J Med. 2005 Aug 25;353(8):770-81. doi: 10.1056/NEJMoa050085.
Results Reference
background
PubMed Identifier
20415897
Citation
Vincenti F, Charpentier B, Vanrenterghem Y, Rostaing L, Bresnahan B, Darji P, Massari P, Mondragon-Ramirez GA, Agarwal M, Di Russo G, Lin CS, Garg P, Larsen CP. A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant. 2010 Mar;10(3):535-46. doi: 10.1111/j.1600-6143.2009.03005.x.
Results Reference
background
PubMed Identifier
21076381
Citation
Larsen CP, Grinyo J, Medina-Pestana J, Vanrenterghem Y, Vincenti F, Breshahan B, Campistol JM, Florman S, Rial Mdel C, Kamar N, Block A, Di Russo G, Lin CS, Garg P, Charpentier B. Belatacept-based regimens versus a cyclosporine A-based regimen in kidney transplant recipients: 2-year results from the BENEFIT and BENEFIT-EXT studies. Transplantation. 2010 Dec 27;90(12):1528-35. doi: 10.1097/TP.0b013e3181ff87cd.
Results Reference
background
PubMed Identifier
30866104
Citation
Sparkes T, Ravichandran B, Opara O, Ugarte R, Drachenberg CB, Philosophe B, Bromberg JS, Barth RN. Alemtuzumab induction and belatacept maintenance in marginal pathology renal allografts. Clin Transplant. 2019 Jun;33(6):e13531. doi: 10.1111/ctr.13531. Epub 2019 Apr 11.
Results Reference
derived
Links:
URL
http://umm.edu/transplant
Description
University of Maryland Division of Transplantation

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Belatacept in Renal Transplantation With Intermediate Risk Maryland Aggregate Pathology Index (MAPI) Scores

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