1 / 27

Setting up clinical trials in WM

EWMnetwork London 16.8.2014. Setting up clinical trials in WM. Prof. Dr. C . Buske. Waldenström Macroglobulinemia (WM) Our Challenges. A rare disease with all implications! No lobby No major ‘economic’ interest of pharmaceutical companies

bertha
Download Presentation

Setting up clinical trials in WM

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. EWMnetwork London 16.8.2014 Setting upclinicaltrials in WM Prof. Dr. C. Buske

  2. WaldenströmMacroglobulinemia (WM)Our Challenges • A rare disease with all implications! • No lobby • No major ‘economic’ interest of pharmaceutical companies • No deep knowledge about this disease in the community of physicians • No major interest to participate in clinical trials for physicians • Scattered activity in academia • Poor coordination of clinical trial activity • Nearly no major phase III trials performed until today Jan G. Waldenström, MD Waldenström J Acta Medica Scandinaviva 1944

  3. WaldenströmMacroglobulinemia (WM)How can we overcome all this? • Working together • Forming networks • Speaking with one voice • Coordinating forces and resources • Patients on one side • We as physicians on the other side Jan G. Waldenström, MD Waldenström J Acta Medica Scandinaviva 1944

  4. Where to go now in Europe

  5. Foundation of a New Consortium European Consortium for Waldenström’sMacroglobulinemia (ECWM)

  6. Members - ECWM + Austrian Study Group (U. Jäger) + Czech Lymphoma Study Group (R. Hajek) + Polish Study Group (T. Robak) + Swiss Study Group (SAKK) + Association ALLG (Australian Study Group)

  7. Pathology Panel - ECWM

  8. http://www.ecwm.eu/

  9. Our Goals: -- settingupclinicaltrials -- settingup national registrieswiththeultimategoalof a pan-European registry -- settingupbiosamplingwith a European biobankfor WM -- fosteringtranslationalresearch („frombenchtobedside“) -- beingrepresented in all majortreatmentguidelines  Making thediseasemore ‚public‘

  10. Our Goals: Togetherwithourpatientsandpatientnetworks!

  11. ECWM Meeting 8th International Workshop on WM London August 14th, 2014 Agenda: nECWM-1 trial (C. Buske) nECWM-R1 trial (M. Dimopoulos) nPlanned phase II trials -- Rituximab/Idelalisib (P. Morel, V. Leblond)       -- Rituximab/Abt-199 (C. Buske)       -- Rituximab/Oprozomib/Dexamethasone (S. Rassam)       -- Ixazomib/Rituximab/Dexamethasone (M. Kersten) nNational Registries       -- Sweden (E. Kimby/L. Brandefors)       -- Czech Rep (R. Hajek)       -- Germany (C. Buske) -- European WM Patient Record Study (C. Buske, M. Dimopoulos) nHorizon 2020 (R. Garcia Sanz, R. Owen, C. Buske) nMiscellaneous (all)

  12. Clinical Trial Activity – ECWM - 1

  13. Study Flow Registration Randomisation Standard Arm 6 x DRC Experimental Arm 6 x B - DRC SD, PD Follow-upforsurvival SD, PD Follow-upforsurvival Follow – up Forresponseuntilprogression For OS untildeath

  14. Clinical Trial Activity – ECWM - 1

  15. Clinical Trial Activity – ECWM - 1

  16. Clinical Trial Activity – ECWM – 1 Rituxi.v.ands.c. will be providedby Roche

  17. Bruton’sTyrosine Kinase (BTK):A Critical Kinasefor Lymphoma Cell Survival and Proliferation • Bruton’styrosine kinase (BTK) is an essential element of the BCR signaling pathway • Inhibitors of BTK block BCR signaling and induce apoptosis • PCI-32765 (ibrutinib) forms bond with cysteine-481 in BTK • Highly potent BTK inhibition at IC50 = 0.5 nM • High degree of B-cell specificity • Orally administered once daily dosing 3

  18. A randomized phase III study of Ibrutinib p.o. versus extended Rituximab i.v. therapy in patients with previously treated WM ECWM-R1 European Waldenström's Macroglobulinemia Consortium ECWM-R1 Version 1.1

  19. Study design • European/Australian phase III trial, multicenter, open label, and randomized • Study population: Previously treated patients with WM who have received 1 to 3 prior lines of therapy EWMC-R1 Version 1.1

  20. Objectives • Primary study objective is Progression Free Survival (PFS) • Secondary study objectives • Response rate (CR, VGPR, PR, MR) and (ORR) • Toxicity • best response • time to best response • time to first response • time to treatment failure • remission duration • cause specific survival & overall survival EWMC-R1 Version 1.1

  21. Clinical Trial Activity – ECWM - R1 Filing for EMA planned!

  22. ECWM-R1 / Relapse Rituximb 375 mg/m2 IV weekly for 4 consecutive weeks – week 1-4 and week 13-16 plus Placebo 1 : 1 R Rituximab plus oral Ibrutinib 420 mg qD continuously until evidence of progressive disease plus Ibrutinib Crossover: Patients who are randomized in the rituximab arm and demonstrate progressive disease, will be allowed to receive ibrutinib

  23. Guidelines

  24. Treatment Algorithms – WMNational LevelDGHO

  25. Treatment Algorithms - WM ESMO Guidelines Buske et al., 2014

  26. Manythanks

More Related