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.
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
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 3(rd) (arm A + B) and the 5(th) 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.


CONCLUSIONS
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.


BACKGROUND
ISRCTN16345835 (date of registration 2010-08-24).
Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Marc-Andrea
MA
Baertsch
Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Jana
J
Schlenzka
Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Elias K
EK
Mai
Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Maximilian
M
Merz
Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Jens
J
Hillengaß
Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Marc S
MS
Raab
Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Dirk
D
Hose
Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Patrick
P
Wuchter
Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Anthony D
AD
Ho
Institute for Human Genetics, University of Heidelberg, Heidelberg, Germany.
Anna
A
Jauch
Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
Thomas
T
Hielscher
Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
Christina
C
Kunz
Coordination Centre for Clinical Trials (KKS), University Hospital Heidelberg, Heidelberg, Germany.
Steffen
S
Luntz
Hematology and Oncology, University Hospital Mannheim, Mannheim, Germany.
Stefan
S
Klein
Center for Integrated Oncology, Med. Klinik und Poliklinik III, University Hospital Bonn, Bonn, Germany.
Ingo G H
IG
Schmidt-Wolf
Hematology, Oncology and Palliative Care, Community Hospital Bielefeld, Bielefeld, Germany.
Martin
M
Goerner
Hematology and Oncology, Helios-Hospital Berlin Buch, Berlin, Germany.
Martin
M
Schmidt-Hieber
Hematology, Oncology and Stem Cell Transplantation, Evangelisches Krankenhaus Essen-Werden gGmbH, Essen, Germany.
Peter
P
Reimer
Hematology, Oncology and Gastroenterology, Maria-Hilf-Krankenhaus, Mönchengladbach, Germany.
Ullrich
U
Graeven
Hematology, Oncology and Clinical Immunology, University of Duesseldorf, Duesseldorf, Germany.
Roland
R
Fenk
Hematology, Oncology and Palliative Care, Asklepios Klinik Altona, Hamburg, Germany.
Hans
H
Salwender
Department I of Internal Medicine, University of Cologne, Cologne, Germany.
Christof
C
Scheid
Internal Medicine III, Charité Campus Benjamin Franklin, Berlin, Germany.
Axel
A
Nogai
Hematology, Oncology and Stem Cell Transplantation, Klinikum Chemnitz GmbH, Chemnitz, Germany.
Mathias
M
Haenel
Hematology and Oncology, Kath. Krankenhaus Hagen gem. GmbH - St.-Marien-Hospital, Hagen, Germany.
Hans W
HW
Lindemann
Hematology and Oncology, Goethe University, Frankfurt, Germany.
Hans
H
Martin
Hematology, University Hospital Essen, Essen, Germany.
Richard
R
Noppeney
Hematology, Oncology and Immunology, University of Tuebingen, Tuebingen, Germany.
Katja
K
Weisel
Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany. Hartmut.Goldschmidt@med.uni-heidelberg.de.|National Center for Tumor Diseases, Heidelberg University Hospital, Heidelberg, Germany. Hartmut.Goldschmidt@med.uni-heidelberg.de.
Hartmut
H
Goldschmidt
D000328:Adult; D000368:Aged; D003907:Dexamethasone / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D012008:Recurrence; D016879:Salvage Therapy; D033581:Stem Cell Transplantation; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014182:Transplantation, Autologous
D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide
Autologous stem cell transplantation; High-dose chemotherapy; Lenalidomide; Multiple myeloma; Relapse; Second-line treatment