Belatacept Pilot Study in Lung Transplantation Immunosuppression in Lung Transplantation

Summary

This is a pilot randomized controlled trial examining the feasibility of conducting a large scale randomized controlled trial of belatacept-based immunosuppression in lung transplantation. This pilot study will enroll 40 lung transplant recipients and randomize them to belatacept-based immunosuppression or standard of care. The primary endpoint of the study is the development of donor-specific HLA antibodies after transplantation. All study participants will be followed for a minimum of 12 months after transplantation.

Timeline

Start

2019-12-17

Primary completion

2022-08-31

Completion

2022-08-31

Publications

• Background Yusen RD, Edwards LB, Kucheryavaya AY, Benden C, Dipchand AI, Goldfarb SB, Levvey BJ, Lund LH, Meiser B, Rossano JW, Stehlik J. The Registry of the International Society for Heart and Lung Transplantation: Thirty-second Official Adult Lung and Heart-Lung Transplantation Report--2015; Focus Theme: Early Graft Failure. J Heart Lung Transplant. 2015 Oct;34(10):1264-77. doi: 10.1016/j.healun.2015.08.014. Epub 2015 Sep 3. No abstract available.
• Background Estenne M, Maurer JR, Boehler A, Egan JJ, Frost A, Hertz M, Mallory GB, Snell GI, Yousem S. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant. 2002 Mar;21(3):297-310. doi: 10.1016/s1053-2498(02)00398-4. No abstract available.
• Background Verleden GM, Raghu G, Meyer KC, Glanville AR, Corris P. A new classification system for chronic lung allograft dysfunction. J Heart Lung Transplant. 2014 Feb;33(2):127-33. doi: 10.1016/j.healun.2013.10.022. Epub 2013 Oct 24.
• Background Meyer KC, Raghu G, Verleden GM, Corris PA, Aurora P, Wilson KC, Brozek J, Glanville AR; ISHLT/ATS/ERS BOS Task Force Committee; ISHLT/ATS/ERS BOS Task Force Committee. An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome. Eur Respir J. 2014 Dec;44(6):1479-503. doi: 10.1183/09031936.00107514. Epub 2014 Oct 30.
• Background Lama VN, Murray S, Lonigro RJ, Toews GB, Chang A, Lau C, Flint A, Chan KM, Martinez FJ. Course of FEV(1) after onset of bronchiolitis obliterans syndrome in lung transplant recipients. Am J Respir Crit Care Med. 2007 Jun 1;175(11):1192-8. doi: 10.1164/rccm.200609-1344OC. Epub 2007 Mar 8.
• Background Finlen Copeland CA, Snyder LD, Zaas DW, Turbyfill WJ, Davis WA, Palmer SM. Survival after bronchiolitis obliterans syndrome among bilateral lung transplant recipients. Am J Respir Crit Care Med. 2010 Sep 15;182(6):784-9. doi: 10.1164/rccm.201002-0211OC. Epub 2010 May 27.
• Background Singer JP, Singer LG. Quality of life in lung transplantation. Semin Respir Crit Care Med. 2013 Jun;34(3):421-30. doi: 10.1055/s-0033-1348470. Epub 2013 Jul 2.
• Background Daud SA, Yusen RD, Meyers BF, Chakinala MM, Walter MJ, Aloush AA, Patterson GA, Trulock EP, Hachem RR. Impact of immediate primary lung allograft dysfunction on bronchiolitis obliterans syndrome. Am J Respir Crit Care Med. 2007 Mar 1;175(5):507-13. doi: 10.1164/rccm.200608-1079OC. Epub 2006 Dec 7.
• Background Glanville AR, Aboyoun CL, Havryk A, Plit M, Rainer S, Malouf MA. Severity of lymphocytic bronchiolitis predicts long-term outcome after lung transplantation. Am J Respir Crit Care Med. 2008 May 1;177(9):1033-40. doi: 10.1164/rccm.200706-951OC. Epub 2008 Feb 8.
• Background Hachem RR, Khalifah AP, Chakinala MM, Yusen RD, Aloush AA, Mohanakumar T, Patterson GA, Trulock EP, Walter MJ. The significance of a single episode of minimal acute rejection after lung transplantation. Transplantation. 2005 Nov 27;80(10):1406-13. doi: 10.1097/01.tp.0000181161.60638.fa.
• Background Le Pavec J, Suberbielle C, Lamrani L, Feuillet S, Savale L, Dorfmuller P, Stephan F, Mussot S, Mercier O, Fadel E. De-novo donor-specific anti-HLA antibodies 30 days after lung transplantation are associated with a worse outcome. J Heart Lung Transplant. 2016 Sep;35(9):1067-77. doi: 10.1016/j.healun.2016.05.020. Epub 2016 May 31.
• Background Tikkanen JM, Singer LG, Kim SJ, Li Y, Binnie M, Chaparro C, Chow CW, Martinu T, Azad S, Keshavjee S, Tinckam K. De Novo DQ Donor-Specific Antibodies Are Associated with Chronic Lung Allograft Dysfunction after Lung Transplantation. Am J Respir Crit Care Med. 2016 Sep 1;194(5):596-606. doi: 10.1164/rccm.201509-1857OC.
• Background Girnita AL, McCurry KR, Iacono AT, Duquesnoy R, Corcoran TE, Awad M, Spichty KJ, Yousem SA, Burckart G, Dauber JH, Griffith BP, Zeevi A. HLA-specific antibodies are associated with high-grade and persistent-recurrent lung allograft acute rejection. J Heart Lung Transplant. 2004 Oct;23(10):1135-41. doi: 10.1016/j.healun.2003.08.030.
• Background Girnita AL, Duquesnoy R, Yousem SA, Iacono AT, Corcoran TE, Buzoianu M, Johnson B, Spichty KJ, Dauber JH, Burckart G, Griffith BP, McCurry KR, Zeevi A. HLA-specific antibodies are risk factors for lymphocytic bronchiolitis and chronic lung allograft dysfunction. Am J Transplant. 2005 Jan;5(1):131-8. doi: 10.1111/j.1600-6143.2004.00650.x.
• Background Bharat A, Kuo E, Steward N, Aloush A, Hachem R, Trulock EP, Patterson GA, Meyers BF, Mohanakumar T. Immunological link between primary graft dysfunction and chronic lung allograft rejection. Ann Thorac Surg. 2008 Jul;86(1):189-95; discussion 196-7. doi: 10.1016/j.athoracsur.2008.03.073.
• Background Jaramillo A, Smith CR, Maruyama T, Zhang L, Patterson GA, Mohanakumar T. Anti-HLA class I antibody binding to airway epithelial cells induces production of fibrogenic growth factors and apoptotic cell death: a possible mechanism for bronchiolitis obliterans syndrome. Hum Immunol. 2003 May;64(5):521-9. doi: 10.1016/s0198-8859(03)00038-7.
• Background Maruyama T, Jaramillo A, Narayanan K, Higuchi T, Mohanakumar T. Induction of obliterative airway disease by anti-HLA class I antibodies. Am J Transplant. 2005 Sep;5(9):2126-34. doi: 10.1111/j.1600-6143.2005.00999.x.
• Background Fukami N, Ramachandran S, Saini D, Walter M, Chapman W, Patterson GA, Mohanakumar T. Antibodies to MHC class I induce autoimmunity: role in the pathogenesis of chronic rejection. J Immunol. 2009 Jan 1;182(1):309-18. doi: 10.4049/jimmunol.182.1.309.
• Background Mohan S, Palanisamy A, Tsapepas D, Tanriover B, Crew RJ, Dube G, Ratner LE, Cohen DJ, Radhakrishnan J. Donor-specific antibodies adversely affect kidney allograft outcomes. J Am Soc Nephrol. 2012 Dec;23(12):2061-71. doi: 10.1681/ASN.2012070664. Epub 2012 Nov 15.
• Background 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.
• Background 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.
• Background Vincenti F, Larsen CP, Alberu J, Bresnahan B, Garcia VD, Kothari J, Lang P, Urrea EM, Massari P, Mondragon-Ramirez G, Reyes-Acevedo R, Rice K, Rostaing L, Steinberg S, Xing J, Agarwal M, Harler MB, Charpentier B. Three-year outcomes from BENEFIT, a randomized, active-controlled, parallel-group study in adult kidney transplant recipients. Am J Transplant. 2012 Jan;12(1):210-7. doi: 10.1111/j.1600-6143.2011.03785.x. Epub 2011 Oct 12.
• Background Streitz M, Miloud T, Kapinsky M, Reed MR, Magari R, Geissler EK, Hutchinson JA, Vogt K, Schlickeiser S, Kverneland AH, Meisel C, Volk HD, Sawitzki B. Standardization of whole blood immune phenotype monitoring for clinical trials: panels and methods from the ONE study. Transplant Res. 2013 Oct 25;2(1):17. doi: 10.1186/2047-1440-2-17.
• Huang HJ, Schechtman K, Askar M, Bernadt C, Mitter B, Dore P, Goodarzi A, Yau S, Youssef JG, Witt CA, Byers DE, Vazquez-Guillamet R, Halverson L, Nava R, Puri V, Kreisel D, Gelman AE, Hachem RR. A Pilot Randomized Controlled Trial of De Novo Belatacept-based Immunosuppression After Lung Transplantation. Transplantation. 2024 Mar 1;108(3):777-786. doi: 10.1097/TP.0000000000004841. Epub 2024 Feb 20.

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