Belatacept in Kidney Transplantation of Moderately Sensitized Patients
NCT ID: NCT02130817
Last Updated: 2018-12-17
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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WITHDRAWN
PHASE4
INTERVENTIONAL
2014-09-24
2015-10-09
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Belatacept
Belatacept (nujolix):
Tacrolimus withdrawal
Standard of care(SOC) treatment:
Plasmapheresis/Intravenous Immunoglobulin G (IVIG) therapy
Thymoglobulin will be administered to a total cumulative dose of 4.5-6 mg/kg starting in the operating room.
Maintenance immunosuppression:
Myfortic: Patients will receive 720mg bid of Myfortic throughout the study, starting day 1 after surgery.
Steroids: Patients will receive Dexamethasone IV on the day of surgery (Day 0) with tapered doses through Day 4 followed by prednisone tapered to 10mg/d by day 30.
Belatacept
Belatacept will be added to the standard of care regimen and will be given at days 0,5, weeks 2, 4, 8 and 12 (10 mg/kg) and every 4 weeks (5 mg/kg) for one year.
Tacrolimus withdrawal
Tacrolimus dosing will begin on Days 1 through 5 post transplant at up to 2 mg BID to achieve target trough levels of 9-11 ng/ml. The dose will be tapered through the end of week 2 to achieve a trough level of 4 ng/ml which will be maintained for six weeks. Tacrolimus will be withdrawn at the end of eight weeks post transplant.
Plasmapheresis/Intravenous Immunoglobulin G
Enrolled patients will start with standard of practice treatment including plasmapheresis and IVIG therapy twice after transplant, on days 2 and 4 and potentially once before transplant. Plasmapheresis and albumin exchange for one volume of blood will be performed in the infusion center at the University of Wisconsin Hospital and Clinics (UWHC). Each pheresis session will be completed by IVIG infusion. While plasmapheresis will help with the removal of circulating Donor Specific Antibodies (DSA), IVIG therapy will provide immunomodulatory characteristics that include sterilizing immunity from infections, inhibiting and scavenging activated complement fragments, modifying cell-mediated immune responses, inducing regulatory T cells and importantly, inhibiting deleterious antibody production.
Thymoglobulin (ATG)
Thymoglobulin (ATG) Induction. Thymoglobulin will be administered to a total cumulative dose of 4.5-6 mg/kg via a peripheral or central vein, starting in the operating room.
Myfortic
Patients will receive 720mg bid of Myfortic throughout the study, starting day 1 after surgery.
Steroids
Patients will receive Dexamethasone IV on the day of surgery (Day 0) with tapered doses through Day 4 followed by prednisone tapered to 10mg/d by day 30.,
Interventions
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Belatacept
Belatacept will be added to the standard of care regimen and will be given at days 0,5, weeks 2, 4, 8 and 12 (10 mg/kg) and every 4 weeks (5 mg/kg) for one year.
Tacrolimus withdrawal
Tacrolimus dosing will begin on Days 1 through 5 post transplant at up to 2 mg BID to achieve target trough levels of 9-11 ng/ml. The dose will be tapered through the end of week 2 to achieve a trough level of 4 ng/ml which will be maintained for six weeks. Tacrolimus will be withdrawn at the end of eight weeks post transplant.
Plasmapheresis/Intravenous Immunoglobulin G
Enrolled patients will start with standard of practice treatment including plasmapheresis and IVIG therapy twice after transplant, on days 2 and 4 and potentially once before transplant. Plasmapheresis and albumin exchange for one volume of blood will be performed in the infusion center at the University of Wisconsin Hospital and Clinics (UWHC). Each pheresis session will be completed by IVIG infusion. While plasmapheresis will help with the removal of circulating Donor Specific Antibodies (DSA), IVIG therapy will provide immunomodulatory characteristics that include sterilizing immunity from infections, inhibiting and scavenging activated complement fragments, modifying cell-mediated immune responses, inducing regulatory T cells and importantly, inhibiting deleterious antibody production.
Thymoglobulin (ATG)
Thymoglobulin (ATG) Induction. Thymoglobulin will be administered to a total cumulative dose of 4.5-6 mg/kg via a peripheral or central vein, starting in the operating room.
Myfortic
Patients will receive 720mg bid of Myfortic throughout the study, starting day 1 after surgery.
Steroids
Patients will receive Dexamethasone IV on the day of surgery (Day 0) with tapered doses through Day 4 followed by prednisone tapered to 10mg/d by day 30.,
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Patient who is receiving an expanded criteria donor (ECD) or deceased cardiac donor (DCD) kidney
* Have immunodominant donor specific antibodies (DSA) 1,000 - 4,000 mean fluorescent intensity (MFI) by single bead Luminex bioassay
* Subjects must be capable of understanding the investigational nature and risks of the study and must sign a statement of informed consent
* Female patients of child bearing potential must have a negative urine or serum pregnancy test within the past 48 hours prior to study inclusion and be willing to use contraceptives for the duration of the study and for 8 weeks after the last dose of study drug Women of Child-Bearing Potential (WOCBP) includes
* Women who have experienced menarche and who have not undergone successful surgical sterilization or who are not post-menopausal
* Women using oral contraceptives, other hormonal contraceptives, or mechanical products such as intrauterine devices or barrier methods
* Women who are practicing abstinence
* Women who have a partner who is sterile (eg, due to vasectomy).
* Women must not be breast-feeding
* Male subjects must agree to use an acceptable method for contraception for the duration of the study
* Patient must have known positive Epstein-Barr virus (EBV) serostatus
Exclusion Criteria
* Patient is receiving an human leukocyte antigen (HLA) identical living donor transplant
* Patient who is a recipient of a multiple organ transplant
* Patient with a positive T or B cell crossmatch
* Patient with a donor specific antibody (DSA) as deemed by the local PI to be associated with significant risk of rejection
* Patient has received an ABO incompatible donor kidney
* Recipients will be receiving a dual or en bloc kidney transplant
* Donor anticipated cold ischemia is \> 30hours
* Recipient or donor is known to be seropositive for hepatitis C virus (HCV) or B virus (HBV) except for hepatitis B surface antibody positive. HCV seropositive patients with a negative HCV viral load testing may be included.
* Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV)
* Seronegative or unknown EBV serostatus
* Patient has uncontrolled concomitant infection or any other unstable medical condition that could interfere with the study objectives
* Patients with tuberculosis who have not been treated for latent infection.
* Patients at high risk for polyoma virus-associated nephropathy, which is mostly due to BK virus infection
* Patients at high risk for polyoma virus-associated nephropathy, which is mostly due to BK virus infection
* Patients with thrombocytopenia (PLT \<75,000/mm3), and/or leucopoenia (WBC \< 2,000/mm3), or anemia (hemoglobin \< 6 g/dL) prior to study inclusion.
* Patient is taking or has been taking an investigational drug in the 30 days prior to transplant
* Patient who has undergone desensitization therapy within 6 months prior to transplant
* Patient has a known hypersensitivity to belatacept, tacrolimus, mycophenolate mofetil, alemtuzumab, rabbit anti-thymocyte globulin, or glucocorticoids
* Patient is receiving chronic steroid therapy at the time of transplant
* Patients with a history of cancer (other than non-melanoma skin cell cancers cured by local resection) within the last 5 years
* Patients with \> Grade 2 peripheral neuropathy within 14 days before enrollment
* Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiography evidence of acute ischemia or active conduction system abnormalities.
* Female subject is pregnant or breast-feeding
* Serious medical or psychiatric illness likely to interfere with participation in this clinical study. Subjects who are compulsorily detained for treatment of either a psychiatric or physical illness
* Prisoners or subjects who are involuntarily incarcerated
18 Years
70 Years
ALL
No
Sponsors
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Bristol-Myers Squibb
INDUSTRY
University of Wisconsin, Madison
OTHER
Responsible Party
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Principal Investigators
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Arjang Djamali, M.D.
Role: PRINCIPAL_INVESTIGATOR
University of Wisconsin, Madison
Locations
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University of Wiscsonsin Hospital and Clinics
Madison, Wisconsin, United States
Countries
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References
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Trivedi HL, Terasaki PI, Feroz A, Everly MJ, Vanikar AV, Shankar V, Trivedi VB, Kaneku H, Idica AK, Modi PR, Khemchandani SI, Dave SD. Abrogation of anti-HLA antibodies via proteasome inhibition. Transplantation. 2009 May 27;87(10):1555-61. doi: 10.1097/TP.0b013e3181a4b91b.
Jordan SC, Pescovitz MD. Presensitization: the problem and its management. Clin J Am Soc Nephrol. 2006 May;1(3):421-32. doi: 10.2215/CJN.01651105. Epub 2006 Apr 12.
Stegall MD, Gloor J, Winters JL, Moore SB, Degoey S. A comparison of plasmapheresis versus high-dose IVIG desensitization in renal allograft recipients with high levels of donor specific alloantibody. Am J Transplant. 2006 Feb;6(2):346-51. doi: 10.1111/j.1600-6143.2005.01178.x.
Vo AA, Lukovsky M, Toyoda M, Wang J, Reinsmoen NL, Lai CH, Peng A, Villicana R, Jordan SC. Rituximab and intravenous immune globulin for desensitization during renal transplantation. N Engl J Med. 2008 Jul 17;359(3):242-51. doi: 10.1056/NEJMoa0707894.
Montgomery RA, Zachary AA. Transplanting patients with a positive donor-specific crossmatch: a single center's perspective. Pediatr Transplant. 2004 Dec;8(6):535-42. doi: 10.1111/j.1399-3046.2004.00214.x.
Magee CC, Felgueiras J, Tinckam K, Malek S, Mah H, Tullius S. Renal transplantation in patients with positive lymphocytotoxicity crossmatches: one center's experience. Transplantation. 2008 Jul 15;86(1):96-103. doi: 10.1097/TP.0b013e318176ae2c.
Thielke JJ, West-Thielke PM, Herren HL, Bareato U, Ommert T, Vidanovic V, Campbell-Lee SA, Tzvetanov IG, Sankary HN, Kaplan B, Benedetti E, Oberholzer J. Living donor kidney transplantation across positive crossmatch: the University of Illinois at Chicago experience. Transplantation. 2009 Jan 27;87(2):268-73. doi: 10.1097/TP.0b013e3181919a16.
Jordan SC, Toyoda M, Vo AA. Intravenous immunoglobulin a natural regulator of immunity and inflammation. Transplantation. 2009 Jul 15;88(1):1-6. doi: 10.1097/TP.0b013e3181a9e89a.
Investigator Brochure. Belatacept (BMS-2224818), Version 13. Bristol-Myers Squibb Research and Development Department. 15 December 2010.
U.S. Prescribing information for Nulojix® (belatacept), Revised 06/2011. Bristol-Myers Squibb.
Other Identifiers
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IM103-327
Identifier Type: OTHER
Identifier Source: secondary_id
Should be 2013-0672
Identifier Type: -
Identifier Source: org_study_id