BrEPEM-LH-22017 for Older Patients With Untreated Hodgkin Lymphoma (HL)

Summary

The purpose of the phase Ib of the study is to identify the maximum tolerated dose (MTD) of Brentuximab Vedotin (BV) in combination with EPEM and to assess the toxicity of the combination of BV with EPEM. In the phase II efficacy will be evaluated.Besides, progression-free survival (PFS), event-free survival (EFS), overall survival (OS), the duration of response, the overall response rate (ORR) based on best response will be evaluated

Timeline

Start

2018-08-08

Primary completion

2023-10-30

Completion

2024-10-30

Publications

• Background Evens AM, Sweetenham JW, Horning SJ. Hodgkin lymphoma in older patients: an uncommon disease in need of study. Oncology (Williston Park). 2008 Nov 15;22(12):1369-79.
• Background Proctor SJ, Wilkinson J, Sieniawski M. Hodgkin lymphoma in the elderly: a clinical review of treatment and outcome, past, present and future. Crit Rev Oncol Hematol. 2009 Sep;71(3):222-32. doi: 10.1016/j.critrevonc.2008.12.007.
• Background Evens AM, Helenowski I, Ramsdale E, Nabhan C, Karmali R, Hanson B, Parsons B, Smith S, Larsen A, McKoy JM, Jovanovic B, Gregory S, Gordon LI, Smith SM. A retrospective multicenter analysis of elderly Hodgkin lymphoma: outcomes and prognostic factors in the modern era. Blood. 2012 Jan 19;119(3):692-5. doi: 10.1182/blood-2011-09-378414. Epub 2011 Nov 23.
• Background Engert A, Ballova V, Haverkamp H, Pfistner B, Josting A, Duhmke E, Muller-Hermelink K, Diehl V; German Hodgkin's Study Group. Hodgkin's lymphoma in elderly patients: a comprehensive retrospective analysis from the German Hodgkin's Study Group. J Clin Oncol. 2005 Aug 1;23(22):5052-60. doi: 10.1200/JCO.2005.11.080. Epub 2005 Jun 13.
• Background Ballova V, Ruffer JU, Haverkamp H, Pfistner B, Muller-Hermelink HK, Duhmke E, Worst P, Wilhelmy M, Naumann R, Hentrich M, Eich HT, Josting A, Loffler M, Diehl V, Engert A. A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly). Ann Oncol. 2005 Jan;16(1):124-31. doi: 10.1093/annonc/mdi023.
• Background Halbsguth TV, Boll B, Borchmann P, Diehl V. The unique characteristics and management of patients over 60 years of age with classic Hodgkin lymphoma. Curr Hematol Malig Rep. 2011 Sep;6(3):164-71. doi: 10.1007/s11899-011-0089-7.
• Background Proctor SJ, Rueffer JU, Angus B, Breuer K, Flechtner H, Jarrett R, Levis A, Taylor P, Tirelli U. Hodgkin's disease in the elderly: current status and future directions. Ann Oncol. 2002;13 Suppl 1:133-7. doi: 10.1093/annonc/13.s1.133.
• Background Halbsguth TV, Nogova L, Mueller H, Sieniawski M, Eichenauer DA, Schober T, Nisters-Backes H, Borchmann P, Diehl V, Engert A, Josting A. Phase 2 study of BACOPP (bleomycin, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) in older patients with Hodgkin lymphoma: a report from the German Hodgkin Study Group (GHSG). Blood. 2010 Sep 23;116(12):2026-32. doi: 10.1182/blood-2009-11-253211. Epub 2010 Jun 15.
• Background Boll B, Bredenfeld H, Gorgen H, Halbsguth T, Eich HT, Soekler M, Markova J, Keller U, Graeven U, Kremers S, Geissler M, Trenn G, Fuchs M, von Tresckow B, Eichenauer DA, Borchmann P, Engert A. Phase 2 study of PVAG (prednisone, vinblastine, doxorubicin, gemcitabine) in elderly patients with early unfavorable or advanced stage Hodgkin lymphoma. Blood. 2011 Dec 8;118(24):6292-8. doi: 10.1182/blood-2011-07-368167. Epub 2011 Sep 13.
• Background Levis A, Anselmo AP, Ambrosetti A, Adamo F, Bertini M, Cavalieri E, Gavarotti P, Genua A, Liberati M, Pavone V, Pietrasanta D, Ricetti MM, Scalabrini DR, Salvi F, Vitolo U, Angelucci E, Boccadoro M, Gallo E, Mandelli F; Intergruppo Italiano Linfomi (IIL). VEPEMB in elderly Hodgkin's lymphoma patients. Results from an Intergruppo Italiano Linfomi (IIL) study. Ann Oncol. 2004 Jan;15(1):123-8. doi: 10.1093/annonc/mdh012.
• Background Proctor SJ, Wilkinson J, Jones G, Watson GC, Lucraft HH, Mainou-Fowler T, Culligan D, Galloway MJ, Wood KM, McNally RJ, James PW, Goodlad JR. Evaluation of treatment outcome in 175 patients with Hodgkin lymphoma aged 60 years or over: the SHIELD study. Blood. 2012 Jun 21;119(25):6005-15. doi: 10.1182/blood-2011-12-396556. Epub 2012 May 10.
• Background Francisco JA, Cerveny CG, Meyer DL, Mixan BJ, Klussman K, Chace DF, Rejniak SX, Gordon KA, DeBlanc R, Toki BE, Law CL, Doronina SO, Siegall CB, Senter PD, Wahl AF. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003 Aug 15;102(4):1458-65. doi: 10.1182/blood-2003-01-0039. Epub 2003 Apr 24.
• Background Okeley NM, Miyamoto JB, Zhang X, Sanderson RJ, Benjamin DR, Sievers EL, Senter PD, Alley SC. Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. Clin Cancer Res. 2010 Feb 1;16(3):888-97. doi: 10.1158/1078-0432.CCR-09-2069. Epub 2010 Jan 19.
• Background Cerveny CG, Law CL, McCormick RS, Lenox JS, Hamblett KJ, Westendorf LE, Yamane AK, Petroziello JM, Francisco JA, Wahl AF. Signaling via the anti-CD30 mAb SGN-30 sensitizes Hodgkin's disease cells to conventional chemotherapeutics. Leukemia. 2005 Sep;19(9):1648-55. doi: 10.1038/sj.leu.2403884.
• Background Wahl AF, Klussman K, Thompson JD, Chen JH, Francisco LV, Risdon G, Chace DF, Siegall CB, Francisco JA. The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin's disease. Cancer Res. 2002 Jul 1;62(13):3736-42.
• Background Younes A, Bartlett NL, Leonard JP, Kennedy DA, Lynch CM, Sievers EL, Forero-Torres A. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010 Nov 4;363(19):1812-21. doi: 10.1056/NEJMoa1002965.
• Background Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, Forero-Torres A, Moskowitz CH, Connors JM, Engert A, Larsen EK, Kennedy DA, Sievers EL, Chen R. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol. 2012 Jun 20;30(18):2183-9. doi: 10.1200/JCO.2011.38.0410. Epub 2012 Mar 26.
• Background Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989 Mar;10(1):1-10. doi: 10.1016/0197-2456(89)90015-9.

Drugs

Indications