Rationale and design of the German-Speaking Myeloma Multicenter Group (GMMG) trial ReLApsE: 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

BMC Cancer

Study Protocol

Ingo G. H. Schmidt-Wolf¹  Steffen Luntz²  Christof Scheid³  Christina Kunz⁴  Thomas Hielscher⁴  Hans Martin⁵  Martin Schmidt-Hieber⁶  Hans W. Lindemann⁷  Stefan Klein⁸  Roland Fenk⁹  Ullrich Graeven^1,10  Katja Weisel^1,11  Hans Salwender^1,12  Martin Goerner^1,13  Patrick Wuchter^1,14  Marc-Andrea Baertsch^1,14  Elias K. Mai^1,14  Dirk Hose^1,14  Maximilian Merz^1,14  Marc S. Raab^1,14  Jana Schlenzka^1,14  Jens Hillengaß^1,14  Anthony D. Ho^1,14  Hartmut Goldschmidt^1,15  Peter Reimer^1,16  Mathias Haenel^1,17  Richard Noppeney^1,18  Anna Jauch^1,19  Axel Nogai^2,20 

[1] Center for Integrated Oncology, Med. Klinik und Poliklinik III, University Hospital Bonn, Bonn, Germany;Coordination Centre for Clinical Trials (KKS), University Hospital Heidelberg, Heidelberg, Germany;Department I of Internal Medicine, University of Cologne, Cologne, Germany;Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany;Hematology and Oncology, Goethe University, Frankfurt, Germany;Hematology and Oncology, Helios-Hospital Berlin Buch, Berlin, Germany;Hematology and Oncology, Kath. Krankenhaus Hagen gem. GmbH - St.-Marien-Hospital, Hagen, Germany;Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany;Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Duesseldorf, Germany;Hematology, Oncology and Gastroenterology, Maria-Hilf-Krankenhaus, Mönchengladbach, Germany;Hematology, Oncology and Immunology, University of Tuebingen, Tuebingen, Germany;Hematology, Oncology and Palliative Care, Asklepios Klinik Altona, Hamburg, Germany;Hematology, Oncology and Palliative Care, Community Hospital Bielefeld, Bielefeld, Germany;Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany;Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany;National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany;Hematology, Oncology and Stem Cell Transplantation, Evangelisches Krankenhaus Essen-Werden gGmbH, Essen, Germany;Hematology, Oncology and Stem Cell Transplantation, Klinikum Chemnitz GmbH, Chemnitz, Germany;Hematology, University Hospital Essen, Essen, Germany;Institute for Human Genetics, University of Heidelberg, Heidelberg, Germany;Internal Medicine III, Charité Campus Benjamin Franklin, Berlin, Germany;

关键词: Multiple myeloma;    Relapse;    Second-line treatment;    Lenalidomide;    Autologous stem cell transplantation;    High-dose chemotherapy;   

DOI  :  10.1186/s12885-016-2321-2

 received in 2015-09-10, accepted in 2016-04-15,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundDespite 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/DesignReLApsE 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.DiscussionThis 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).

【 授权许可】

CC BY   
© Baertsch et al. 2016