Clinical trial NCT01496417: 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
Overall status: COMPLETED
Phase: NA
Conditions: End-Stage Renal Disease
Keywords: Kidney Transplantation
Biopsy
Belatacept
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2011-12-21
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Renal Function
timeFrame: 12 months
Secondary outcomes:
measure: Rejection rate
timeFrame: 12 months
measure: Graft survival
timeFrame: 12 months
measure: MAPI biopsy score
timeFrame: 12 months
measure: Patient survival
timeFrame: 12 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
Study officials:
affiliation: University of Maryland, Baltimore
name: Rolf N Barth, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.