Open Label Extension Study of Brentuximab Vedotin in Early dcSSc

Summary

The purpose of this study is to assess safety and efficacy of Brentuximab vedotin, a CD30-directed antibody-drug conjugate, in patients with active diffuse cutaneous systemic sclerosis (dcSSc) who relapsed after discontinuation of Brentuximab vedotin.

Timeline

Start

2024-02-14

Primary completion

2026-02-14

Completion

2026-07-01

Publications

• Background Komocsi A, Vorobcsuk A, Faludi R, Pinter T, Lenkey Z, Kolto G, Czirjak L. The impact of cardiopulmonary manifestations on the mortality of SSc: a systematic review and meta-analysis of observational studies. Rheumatology (Oxford). 2012 Jun;51(6):1027-36. doi: 10.1093/rheumatology/ker357. Epub 2012 Jan 5.
• Background Young A, Khanna D. Systemic sclerosis: a systematic review on therapeutic management from 2011 to 2014. Curr Opin Rheumatol. 2015 May;27(3):241-8. doi: 10.1097/BOR.0000000000000172.
• Background Shah AA, Casciola-Rosen L, Rosen A. Review: cancer-induced autoimmunity in the rheumatic diseases. Arthritis Rheumatol. 2015 Feb;67(2):317-26. doi: 10.1002/art.38928. No abstract available.
• Background Andras C, Ponyi A, Constantin T, Csiki Z, Szekanecz E, Szodoray P, Danko K. Dermatomyositis and polymyositis associated with malignancy: a 21-year retrospective study. J Rheumatol. 2008 Mar;35(3):438-44. Epub 2008 Jan 15.
• Background Hasegawa M, Sato S, Sakai H, Ohashi T, Takehara K. Systemic sclerosis revealing T-cell lymphoma. Dermatology. 1999;198(1):75-8. doi: 10.1159/000018070.
• Background Juarez M, Marshall R, Denton C, Evely R. Paraneoplastic scleroderma secondary to hairy cell leukaemia successfully treated with cladribine. Rheumatology (Oxford). 2008 Nov;47(11):1734-5. doi: 10.1093/rheumatology/ken367. Epub 2008 Sep 23. No abstract available.
• Background Khanna D, Berrocal VJ, Giannini EH, Seibold JR, Merkel PA, Mayes MD, Baron M, Clements PJ, Steen V, Assassi S, Schiopu E, Phillips K, Simms RW, Allanore Y, Denton CP, Distler O, Johnson SR, Matucci-Cerinic M, Pope JE, Proudman SM, Siegel J, Wong WK, Wells AU, Furst DE. The American College of Rheumatology Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis. Arthritis Rheumatol. 2016 Feb;68(2):299-311. doi: 10.1002/art.39501.
• Background Valentini G, Silman AJ, Veale D. Assessment of disease activity. Clin Exp Rheumatol. 2003;21(3 Suppl 29):S39-41.
• Background Medsger TA Jr, Bombardieri S, Czirjak L, Scorza R, Della Rossa A, Bencivelli W. Assessment of disease severity and prognosis. Clin Exp Rheumatol. 2003;21(3 Suppl 29):S42-6.
• Background Oflazoglu E, Simpson EL, Takiguchi R, Grewal IS, Hanifin JM, Gerber HP. CD30 expression on CD1a+ and CD8+ cells in atopic dermatitis and correlation with disease severity. Eur J Dermatol. 2008 Jan-Feb;18(1):41-9. doi: 10.1684/ejd.2008.0309. Epub 2007 Dec 18.
• Background Clements P, Lachenbruch P, Siebold J, White B, Weiner S, Martin R, Weinstein A, Weisman M, Mayes M, Collier D, et al. Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis. J Rheumatol. 1995 Jul;22(7):1281-5.
• Background Clements PJ, Lachenbruch PA, Seibold JR, Zee B, Steen VD, Brennan P, Silman AJ, Allegar N, Varga J, Massa M, et al. Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies. J Rheumatol. 1993 Nov;20(11):1892-6.
• Background Furst DE, Khanna D, Mattucci-Cerinic M, Silman AJ, Merkel PA, Foeldvari I; OMERACT 7 Special Interest Group. Scleroderma--developing measures of response. J Rheumatol. 2005 Dec;32(12):2477-80.
• Background Pope JE, Bellamy N. Outcome measurement in scleroderma clinical trials. Semin Arthritis Rheum. 1993 Aug;23(1):22-33. doi: 10.1016/s0049-0172(05)80024-1.
• Background van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, Matucci-Cerinic M, Naden RP, Medsger TA Jr, Carreira PE, Riemekasten G, Clements PJ, Denton CP, Distler O, Allanore Y, Furst DE, Gabrielli A, Mayes MD, van Laar JM, Seibold JR, Czirjak L, Steen VD, Inanc M, Kowal-Bielecka O, Muller-Ladner U, Valentini G, Veale DJ, Vonk MC, Walker UA, Chung L, Collier DH, Csuka ME, Fessler BJ, Guiducci S, Herrick A, Hsu VM, Jimenez S, Kahaleh B, Merkel PA, Sierakowski S, Silver RM, Simms RW, Varga J, Pope JE. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013 Nov;65(11):2737-47. doi: 10.1002/art.38098. Epub 2013 Oct 3.
• Background LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA Jr, Rowell N, Wollheim F. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988 Feb;15(2):202-5. No abstract available.
• Background Sutherland MS, Sanderson RJ, Gordon KA, Andreyka J, Cerveny CG, Yu C, Lewis TS, Meyer DL, Zabinski RF, Doronina SO, Senter PD, Law CL, Wahl AF. Lysosomal trafficking and cysteine protease metabolism confer target-specific cytotoxicity by peptide-linked anti-CD30-auristatin conjugates. J Biol Chem. 2006 Apr 14;281(15):10540-7. doi: 10.1074/jbc.M510026200. Epub 2006 Feb 16.
• Background Ong VH, Denton CP. Innovative therapies for systemic sclerosis. Curr Opin Rheumatol. 2010 May;22(3):264-72. doi: 10.1097/BOR.0b013e328337c3d6.
• Background Becker MO, Bruckner C, Scherer HU, Wassermann N, Humrich JY, Hanitsch LG, Schneider U, Kawald A, Hanke K, Burmester GR, Riemekasten G. The monoclonal anti-CD25 antibody basiliximab for the treatment of progressive systemic sclerosis: an open-label study. Ann Rheum Dis. 2011 Jul;70(7):1340-1. doi: 10.1136/ard.2010.137935. Epub 2010 Nov 10. No abstract available.
• Background Oon S, Huq M, Godfrey T, Nikpour M. Systematic review, and meta-analysis of steroid-sparing effect, of biologic agents in randomized, placebo-controlled phase 3 trials for systemic lupus erythematosus. Semin Arthritis Rheum. 2018 Oct;48(2):221-239. doi: 10.1016/j.semarthrit.2018.01.001. Epub 2018 Jan 6.
• Background Pope J, McBain D, Petrlich L, Watson S, Vanderhoek L, de Leon F, Seney S, Summers K. Imatinib in active diffuse cutaneous systemic sclerosis: Results of a six-month, randomized, double-blind, placebo-controlled, proof-of-concept pilot study at a single center. Arthritis Rheum. 2011 Nov;63(11):3547-51. doi: 10.1002/art.30549.
• Background Gordon JK, Martyanov V, Franks JM, Bernstein EJ, Szymonifka J, Magro C, Wildman HF, Wood TA, Whitfield ML, Spiera RF. Belimumab for the Treatment of Early Diffuse Systemic Sclerosis: Results of a Randomized, Double-Blind, Placebo-Controlled, Pilot Trial. Arthritis Rheumatol. 2018 Feb;70(2):308-316. doi: 10.1002/art.40358. Epub 2017 Dec 29.
• Background Nihtyanova SI, Schreiber BE, Ong VH, Rosenberg D, Moinzadeh P, Coghlan JG, Wells AU, Denton CP. Prediction of pulmonary complications and long-term survival in systemic sclerosis. Arthritis Rheumatol. 2014 Jun;66(6):1625-35. doi: 10.1002/art.38390.
• Background van Laar JM, Farge D, Sont JK, Naraghi K, Marjanovic Z, Larghero J, Schuerwegh AJ, Marijt EW, Vonk MC, Schattenberg AV, Matucci-Cerinic M, Voskuyl AE, van de Loosdrecht AA, Daikeler T, Kotter I, Schmalzing M, Martin T, Lioure B, Weiner SM, Kreuter A, Deligny C, Durand JM, Emery P, Machold KP, Sarrot-Reynauld F, Warnatz K, Adoue DF, Constans J, Tony HP, Del Papa N, Fassas A, Himsel A, Launay D, Lo Monaco A, Philippe P, Quere I, Rich E, Westhovens R, Griffiths B, Saccardi R, van den Hoogen FH, Fibbe WE, Socie G, Gratwohl A, Tyndall A; EBMT/EULAR Scleroderma Study Group. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA. 2014 Jun 25;311(24):2490-8. doi: 10.1001/jama.2014.6368.
• Background Sullivan KM, Goldmuntz EA, Keyes-Elstein L, McSweeney PA, Pinckney A, Welch B, Mayes MD, Nash RA, Crofford LJ, Eggleston B, Castina S, Griffith LM, Goldstein JS, Wallace D, Craciunescu O, Khanna D, Folz RJ, Goldin J, St Clair EW, Seibold JR, Phillips K, Mineishi S, Simms RW, Ballen K, Wener MH, Georges GE, Heimfeld S, Hosing C, Forman S, Kafaja S, Silver RM, Griffing L, Storek J, LeClercq S, Brasington R, Csuka ME, Bredeson C, Keever-Taylor C, Domsic RT, Kahaleh MB, Medsger T, Furst DE; SCOT Study Investigators. Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma. N Engl J Med. 2018 Jan 4;378(1):35-47. doi: 10.1056/nejmoa1703327.
• Background Khanna D, Denton CP, Lin CJF, van Laar JM, Frech TM, Anderson ME, Baron M, Chung L, Fierlbeck G, Lakshminarayanan S, Allanore Y, Pope JE, Riemekasten G, Steen V, Muller-Ladner U, Spotswood H, Burke L, Siegel J, Jahreis A, Furst DE. Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate). Ann Rheum Dis. 2018 Feb;77(2):212-220. doi: 10.1136/annrheumdis-2017-211682. Epub 2017 Oct 24.
• Background Namas R, Tashkin DP, Furst DE, Wilhalme H, Tseng CH, Roth MD, Kafaja S, Volkmann E, Clements PJ, Khanna D; Participants in the Scleroderma Lung Study I and members of the Scleroderma Lung Study II Research Group. Efficacy of Mycophenolate Mofetil and Oral Cyclophosphamide on Skin Thickness: Post Hoc Analyses From Two Randomized Placebo-Controlled Trials. Arthritis Care Res (Hoboken). 2018 Mar;70(3):439-444. doi: 10.1002/acr.23282. Epub 2018 Feb 9.
• Background Gazi H, Pope JE, Clements P, Medsger TA, Martin RW, Merkel PA, Kahaleh B, Wollheim FA, Baron M, Csuka ME, Emery P, Belch JF, Hayat S, Lally EV, Korn JH, Czirjak L, Herrick A, Voskuyl AE, Bruehlmann P, Inanc M, Furst DE, Black C, Ellman MH, Moreland LW, Rothfield NF, Hsu V, Mayes M, McKown KM, Krieg T, Siebold JR. Outcome measurements in scleroderma: results from a delphi exercise. J Rheumatol. 2007 Mar;34(3):501-9. Epub 2007 Feb 1.
• Background Daoussis D, Melissaropoulos K, Sakellaropoulos G, Antonopoulos I, Markatseli TE, Simopoulou T, Georgiou P, Andonopoulos AP, Drosos AA, Sakkas L, Liossis SN. A multicenter, open-label, comparative study of B-cell depletion therapy with Rituximab for systemic sclerosis-associated interstitial lung disease. Semin Arthritis Rheum. 2017 Apr;46(5):625-631. doi: 10.1016/j.semarthrit.2016.10.003. Epub 2016 Oct 13.
• Background Ramiro S, Sepriano A, Chatzidionysiou K, Nam JL, Smolen JS, van der Heijde D, Dougados M, van Vollenhoven R, Bijlsma JW, Burmester GR, Scholte-Voshaar M, Falzon L, Landewe RBM. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2017 Jun;76(6):1101-1136. doi: 10.1136/annrheumdis-2016-210708. Epub 2017 Mar 15.

Drugs

Indications