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Elotuzumab in Combination With Carfilzomib, Lenalidomide and Dexamethasone (E-KRd) Versus KRd in MM
Sponsor: Wuerzburg University Hospital
Summary
Of the next-generation compounds, the monoclonal antibodies (moAbs) have recently attracted a lot of interest in MM. The anti-SLAMF7 directed moAb elotuzumab has completed phase III trials in MM patients. One phase III trial in MM patients with one to three prior lines of therapy compared elotuzumab-Rd with standard Rd. The triple combination was shown to significantly prolong PFS in this patient cohort with a greater proportion of patients in at least very good partial response (VGPR) when compared to subjects on Rd. Notably, the rate of infusion-related reactions with this specific moAb was very low, with an overall rate of 10% in premedicated patients and only 1% of Grade 3 severity. Grades 4/5 infusion-related reactions were absent and only 1% of patients on elotuzumab discontinued for infusion-related reactions. Of particular interest is the observation in this trial, that response and PFS were independent of cytogenetic high-risk features, i.e., deletion of chromosome 17p and translocation t(4;14). This effect distinguishes elotuzumab from most, if not all, other drug-based approaches. The investigators assume that incorporating the moAb into the KRd triple induction regimen should result in an even higher rate of deep (negative for MRD in conjunction with at least very good partial response \[VGPR\] as defined by the International Myeloma Working Group \[IMWG\]) with these responses occurring independently of cytogenetic risk. Due to potential interference of elotuzumab with serum immune fixation, the investigators chose VGPR rather than complete response (CR) to exclude false-positive immunofixation results. Furthermore the investigators hypothesize that combining elotuzumab with lenalidomide should prolong PFS further.
Official title: Elotuzumab in Combination With Carfilzomib, Lenalidomide and Dexamethasone (E-KRd) Versus KRd Prior to and Following Auto-SCT in Newly Diagnosed Multipe Myeloma and Subsequent Maintenance With Elotuzumab and Lenalidomide Versus Single-Agent Lenalidomide- A Phase III Study by DSMM
Key Details
Gender
All
Age Range
18 Years - 70 Years
Study Type
INTERVENTIONAL
Enrollment
576
Start Date
2018-08-28
Completion Date
2029-08
Last Updated
2023-05-06
Healthy Volunteers
No
Conditions
Interventions
Elotuzumab
i.v. infusion. Induction 6 cycles: 10mg/kg BW D1,8,15,22 of cycle 1 and 2, D1,15 of cycles 3-6. Consolidation 4 cycles: 10mg/kg BW D1,15 of cycle 1-4. Maintenance 28-day cycles: 20mg/kg BW D1 of each 28-day cycle.
Carfilzomib
i.v. infusion. Induction 6 cycles: 20 mg/m² on D1 and 2 of cycle 1, 36 mg/m² on D8, 9, 15, 16 of cycle 1, 36 mg/m² on D1,2,8,9,15,16 of cycle 2-6; Consolidation 4 cycles: 36 mg/m² on days 1, 2, 8, 9, 15, 16 of cycles 1-4.
Lenalidomide
hard capsule for oral use. Induction 6 cycles: 25mg D1-21 of cycle 1-6. Consolidation 4 cycles: 15mg D1-21 of cycle 1, 25mg D1-21 ov cycle 2-4. Maintenance 28-day cycles: 10mg D1-28 of cycle 1,2,3, 15mg D1-28 of cycle 4 and all subsequent cycles.
Dexamethasone
orally and i.v. IN ARM A:Induction 6 cycles: 28mg p.o. and 8mg i.v. D1,8,15,22 of cycles 1-2 and D1,15 of cycles 3-6, 40mg p.o. D8,22 of cycle 3-6. Consolidation 4 cycles: 28mg p.o. and 8mg i.v. D1,15 of cycle 1-4 and 20mg p.o. D8,22 of cycle 1-4. IN ARM B: Induction 6 cycles: 40mg p.o. D1,8,15,22 of cycles 1-6. Consolidation 4 cycles: 20mg p.o. D1,8,15, 22 of cycle 1-4 .
autologous stem cell transplant
autologous stem cell transplant
Locations (56)
Univ. Klinikum Krems
Krems, Lower Austria, Austria
Universitätklinikum St. Pölten
Sankt Pölten, Lower Austria, Austria
LKH-Universitätsklinikum Graz
Graz, Styria, Austria
Medizinische Universität Innsbruck
Innsbruck, Tyrol, Austria
Kepler Universitätsklinikum
Linz, Upper Austria, Austria
Klinikum Wels-Grieskirchen
Wels, Upper Austria, Austria
LKH Rankweil-Feldkirch
Rankweil, Vorarlberg, Austria
Landeskrankenhaus Salzburg
Salzburg, Austria
AKH Meduni Wien
Vienna, Austria
Klinik Ottakring
Vienna, Austria
Universitätsklinikum Freiburg
Freiburg im Breisgau, Baden-Wurttemberg, Germany
Kliniken Ostalb
Mutlangen, Baden-Wurttemberg, Germany
Studienzentrum Onkologie Ravensburg
Ravensburg, Baden-Wurttemberg, Germany
Diakonieklinikum Stuttgart
Stuttgart, Baden-Wurttemberg, Germany
Robert-Bosch Krankenhaus
Stuttgart, Baden-Wurttemberg, Germany
Universitätsklinikum Ulm
Ulm, Baden-Wurttemberg, Germany
Onkologie Schwarzwald-Alb
Villingen-Schwenningen, Baden-Wurttemberg, Germany
Gesundgheitszentrum St. Marien
Amberg, Bavaria, Germany
Klinikum Augsburg
Augsburg, Bavaria, Germany
Sozialstiftung Bamberg
Bamberg, Bavaria, Germany
Klinikum Bayreuth
Bayreuth, Bavaria, Germany
Klinikum Kempten-Oberallgäu
Kempten (Allgäu), Bavaria, Germany
Rotkreuzklinikum München
Munich, Bavaria, Germany
Ludwig-Maximilians-Universität München
Munich, Bavaria, Germany
Klinikum rechts der Isar der TU München
Munich, Bavaria, Germany
Klinikum Nürnberg Nord
Nuremberg, Bavaria, Germany
Uniklinikum Regensburg
Regensburg, Bavaria, Germany
Klinikum Traunstein
Traunstein, Bavaria, Germany
Universitätsklinikum Würzburg, Medizinische Klinik II
Würzburg, Bavaria, Germany
Klinikum der Johann Wolfgang Goethe-Universität Frankfurt am Main
Frankfurt am Main, Hesse, Germany
Universitätsklinikum Göttingen
Göttingen, Lower Saxony, Germany
Med. Hochschule Hannover
Hanover, Lower Saxony, Germany
Klinikum Oldenburg
Oldenburg, Lower Saxony, Germany
Universitätmedizin Greifswald
Greifswald, Mecklenburg-Pomerania, Germany
Universitätsmedizin Rostock
Rostock, Mecklenburg-Pomerania, Germany
Helios Kliniken
Schwerin, Mecklenburg-Pomerania, Germany
Evangelisches Klinikum Bethel
Bielefeld, North Rhine-Westphalia, Germany
St. Johannes Hospital
Dortmund, North Rhine-Westphalia, Germany
St. Barbara-Klinik Hamm
Hamm, North Rhine-Westphalia, Germany
Universitätsklinikum Münster
Münster, North Rhine-Westphalia, Germany
St. Marien-Krankenhaus
Siegen, North Rhine-Westphalia, Germany
Gemeinschaftsklinikum Mittelrhein
Koblenz, Rhineland-Palatinate, Germany
Universitätsklinikum Carl Gustav Carus
Dresden, Saxony, Germany
Universitätsklinikum Leipzig
Leipzig, Saxony, Germany
Universitätsklinikum Halle
Halle, Saxony-Anhalt, Germany
Universitätsklinikum Magdeburg
Magdeburg, Saxony-Anhalt, Germany
Malteser Krankenhaus
Flensburg, Schleswig-Holstein, Germany
Universitätsklinikum Schleswig-Holstein
Kiel, Schleswig-Holstein, Germany
Universitätsklinikum Schleswig-Holstein
Lübeck, Schleswig-Holstein, Germany
Zentralklinik Bad Berka
Bad Berka, Thuringia, Germany
Klinikum der Friedrich-Schiller-Universität Jena
Jena, Thuringia, Germany
Charité Universitätsmedizin Berlin
Berlin, Germany
Helios Kliniken
Berlin, Germany
Vivantes Klinikum Spandau
Berlin, Germany
Klinikum Bremen-Mitte
Bremen, Germany
Asklepios Klinik Altona
Hamburg, Germany