title: Rationale and design of the German-Speaking Myeloma Multicenter Group (GMMG) trial ReLApsE
title: a randomized, open, multicenter phase III trial of lenalidomide/dexamethasone versus lenalidomide/dexamethasone plus subsequent autologous stem cell transplantation and lenalidomide maintenance in patients with relapsed multiple myeloma
titleType: Subtitle
Creators: name: Baertsch, Marc-Andrea
name: Schlenzka, Jana
name: Mai, Elias K.
name: Merz, Maximilian
name: Hillengass, Jens
name: Raab, Marc S.
name: Hose, Dirk
name: Wuchter, Patrick
name: Ho, Anthony D.
name: Jauch, Anna
name: Hielscher, Thomas
name: Kunz, Christina
name: Luntz, Steffen
name: Klein, Stefan
name: Schmidt-Wolf, Ingo G. H.
name: Goerner, Martin
name: Schmidt-Hieber, Martin
name: Reimer, Peter
name: Graeven, Ullrich
name: Fenk, Roland
name: Salwender, Hans
name: Scheid, Christof
name: Nogai, Axel
name: Haenel, Mathias
name: Lindemann, Hans W.
name: Martin, Hans
name: Noppeney, Richard
name: Weisel, Katja
name: Goldschmidt, Hartmut
Publisher: name: Charité - Universitätsmedizin Berlin
Year: 2016
Subjects: subject: Multiple myeloma
subject: Relapse
subject: Second-line treatment
subject: Lenalidomide
subject: Autologous stem cell transplantation
subject: High-dose chemotherapy
subject: 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit

description: Background Despite novel therapeutic agents, most multiple myeloma (MM) patients eventually relapse. Two large phase III trials have shown significantly improved response rates (RR) of lenalidomide/dexamethasone compared with placebo/dexamethasone in relapsed MM (RMM) patients. These results have led to the approval of lenalidomide for RMM patients and lenalidomide/dexamethasone has since become a widely accepted second-line treatment. Furthermore, in RMM patients consolidation with high-dose chemotherapy plus autologous stem cell transplantation has been shown to significantly increase progression free survival (PFS) as compared to cyclophosphamide in a phase III trial. The randomized prospective ReLApsE trial is designed to evaluate PFS after lenalidomide/dexamethasone induction, high-dose chemotherapy consolidation plus autologous stem cell transplantation and lenalidomide maintenance compared with the well-established lenalidomide/dexamethasone regimen in RMM patients. Methods/Design ReLApsE is a randomized, open, multicenter phase III trial in a planned study population of 282 RMM patients. All patients receive three lenalidomide/dexamethasone cycles and - in absence of available stem cells from earlier harvesting - undergo peripheral blood stem cell mobilization and harvesting. Subsequently, patients in arm A continue on consecutive lenalidomide/dexamethasone cycles, patients in arm B undergo high dose chemotherapy plus autologous stem cell transplantation followed by lenalidomide maintenance until discontinuation criteria are met. Therapeutic response is evaluated after the 3rd (arm A + B) and the 5th lenalidomide/dexamethasone cycle (arm A) or 2 months after autologous stem cell transplantation (arm B) and every 3 months thereafter (arm A + B). After finishing the study treatment, patients are followed up for survival and subsequent myeloma therapies. The expected trial duration is 6.25 years from first patient in to last patient out. The primary endpoint is PFS, secondary endpoints include overall survival (OS), RR, time to best response and the influence of early versus late salvage high dose chemotherapy plus autologous stem cell transplantation on OS. Discussion This phase III trial is designed to evaluate whether high dose chemotherapy plus autologous stem cell transplantation and lenalidomide maintenance after lenalidomide/dexamethasone induction improves PFS compared with the well-established continued lenalidomide/dexamethasone regimen in RMM patients. Trial registration: ISRCTN16345835 (date of registration 2010-08-24).