A Phase III Trial on the Effect of Elotuzumab in VRD Induction /Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Myeloma (GMMG-HD6)

A Randomized Phase III Trial on the Effect of Elotuzumab in VRD Induction /Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Myeloma

Trial in patients with newly diagnosed myeloma to evaluate the effect of elotuzumab in induction and consolidation therapy with bortezomib/lenalidomide/dexamethasone and in lenalidomide maintenance treatment

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone; Drug: elotuzumab

Detailed Description

Prospective, multicentre, randomised, parallel group, open, phase III clinical trial, for patients with confirmed diagnosis of untreated multiple myeloma requiring systemic therapy .

Investigational Medicinal Products:Elotuzumab, lenalidomide

Patients are randomized in one of 4 study arms (A1, A2, B1, B2). Patients randomized in arm A1 or A2 will receive 4 cycles VRD (Bortezomib (Velcade®), Lenalidomide (Revlimid®), Dexamethasone). Patients in arm B1 or B2 will additionally receive the monoclonal antibody Elotuzumab in the 4 cycles VRD. After induction therapy patients undergo intensifying therapy according to GMMG standard (usually mobilization therapy followed by stem cell collection and autologous stem cell transplantation). After intensification a consolidation therapy will be performed with two cycles VRD (A1 und B1) or VRD+ Elotuzumab (A2 und B2), followed by Lenalidomide maintenance therapy with (arm A2 and B2) or without (arm A1 and B1) additional Elotuzumab. Maintenance therapy will be performed for 2 years.

Primary objective is the determination of the best of four treatment strategies regarding progression-free survival (PFS), defined as time from randomisation to progression or death from any cause whichever occurs first.

The duration of the trial for each patients is expected to be 36-39 months (induction and intensification treatment: 7-10 months, 3 months rest between intensification and start of consolidation, consolidation 2 months, maintenance phase 24 months).

• Study Type: Interventional
• Enrollment (Actual): 564
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Aschaffenburg, Germany, 63739
    • Studienzentrum Aschaffenburg
  • Baden-Baden, Germany, 76532
    • MVZ Onkologie gGmbH der Klinikum Mittelbaden gGmbH
  • Berlin, Germany, 13125
    • HELIOS Klinikum, Klinik für Hämatologie, Onkologie und Immunologie
  • Berlin, Germany, 13507
    • Onkologisches MVZ Berlin Tegel
  • Berlin, Germany, D-12200
    • Charité Campus Benjamin Franklin, III. Med. Abt. (Hämatologie/Onkologie)
  • Bielefeld, Germany, D-33604
    • Klinikum Bielefeld, Klinik für Hämatologie, Onkologie und Palliativmedizin
  • Bielefeld, Germany, D-33604
    • Studiengesellschaft Onkologie Bielefeld GbR
  • Bochum, Germany, 44787
    • Hämatologisch-Onkologische Schwerpunktpraxis
  • Bochum, Germany, D-44892
    • Medizinische Universitätsklinik, Knappschaftskrankenhaus
  • Bonn, Germany, 53105
    • Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik III, Schwerpunkt Onkologie, Hämatologie und Rheumatologie
  • Bonn, Germany, 53113
    • ZAHO, Zentrum für ambulante Hämatologie und Onkologie
  • Bottrop, Germany, 46236
    • Schwerpunktpraxis für Onkologie/Hämatologie
  • Chemnitz, Germany, D-09116
    • Klinikum Chemnitz GmbH, Innere Medizin III
  • Darmstadt, Germany, 64283
    • Onkologisches Studienzentrum Darmstadt
  • Darmstadt, Germany, D-64283
    • Klinikum Darmstadt, Med. Klinik V, Hämatologie/Onkologie
  • Duisburg, Germany, 47166
    • HELIOS St. Johannes Klinik, Akademisches Krankenhaus der Heinrich-Heine-Universität Düsseldorf
  • Dusseldorf, Germany, 40235
    • MVZ Düsseldorf GmbH
  • Düsseldorf, Germany, D-40225
    • Universitätsklinikum Düsseldorf, Klinik für Hämatologie,Onkologie und Klin. Immunologie
  • Düsseldorf, Germany, 40593
    • Sana Kliniken Düsseldorf GmbH
  • Erlangen, Germany, 91054
    • Universitätsklinik Erlangen
  • Eschweiler, Germany, 52249
    • St.-Antonius-Hospital Klinik f. Hämatologie und Onkologie
  • Essen, Germany, D-45147
    • Universitatsklinikum Essen, Klinik fur Hamatologie
  • Essen, Germany, D-45239
    • Ev. Krankenhaus Essen-Werden gGmbH, Zentrum für Innere Medizin, Klinik für Hämatologie, Onkologie und Stammzelltransplantation
  • Frankfurt am Main, Germany, 60389
    • Centrum für Hämatologie und Onkologie Bethanien
  • Frankfurt am Main, Germany, 60590
    • Universitätsklinikum Frankfurt, Goethe-Universität Medizinische Klinik II
  • Frankfurt/Main, Germany, 60431
    • Agaplesion Markus Krankenhaus
  • Friedrichshafen, Germany, 88045
    • Praxis und Tagesklinik Friedrichshafen
  • Gerlingen, Germany, 70839
    • Gemeinschaftspraxis Schmitt/Eulenbuch
  • Gießen, Germany, 35385
    • Justus-Liebig-Universität, Medizinische Klinik IV
  • Hagen, Germany, D-58095
    • Kath. Krankenhaus Hagen gGmbH, Abt. Hämatologie/Onkologie
  • Hamburg, Germany, D-22763
    • Asklepios Klinik Hamburg Altona, II. Med. Klinik
  • Hamburg, Germany, D-20246
    • Universitätsklinikum Hamburg-Eppendorf, II - Med. Klinik und Poliklinik
  • Hamm, Germany, 59063
    • Evangelisches Krankhaus Hamm gGmbH
  • Heidelberg, Germany, 69115
    • Onkologische Schwerpunktpraxis
  • Heidelberg, Germany, D-69120
    • University Hospital Heidelberg, Med. Klinik V
  • Heilbronn, Germany, 74072
    • Onkologische Schwerpunktpraxis
  • Heilbronn, Germany, D-74078
    • SLK Kliniken Heilbronn, Med. Klinik III
  • Homburg, Germany, 66421
    • Universitätsklinikum des Saarlandes, Innere Medizin I
  • Kaiserslautern, Germany, 67655
    • Westpfalz-Klinikum GmbH
  • Karlsruhe, Germany, 76135
    • Onkologische Schwerpunktpraxis Karlsruhe
  • Kassel, Germany, 34119
    • Onkologische Gemeinschaftspraxis Kassel
  • Koblenz, Germany, D-56068
    • Praxisklinik für Hämatologie und Onkologie
  • Köln, Germany, D-50937
    • Universitätsklinikum Köln, Klinik I - Innere Medizin
  • Lebach, Germany, 66822
    • Onkologisches Zentrum, Gemeinschaftspraxis f. Hämatologie u. Onkologie im Caritas KH
  • Lemgo, Germany, D-32657
    • Klinikum Lippe GmbH, Hämatologie-Onkologie
  • Ludwigsburg, Germany, 71636
    • Schwerpunktpraxis für Hämatologie und Onkologie
  • Ludwigshafen am Rhein, Germany, 67063
    • Med. Klinik A, Klinikum der Stadt Ludwigshafen am Rhein gGmbH
  • Mainz, Germany, D-55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz, III. Med. Klinik
  • Mainz, Germany, 55122
    • Internistische Schwerpunktpraxis für Hämatologie und Onkologie
  • Mannheim, Germany, 68167
    • III. Medizinische Klinik Hämatologie und Internistische Onkologie
  • Mannheim, Germany, D-68161
    • Mannheimer Onkologie Praxis
  • Marburg, Germany, 35032
    • Philipps-Universität Marburg, Hämatologie/Onkologie/Immunologie
  • Minden, Germany, 32429
    • Mühlenkreiskliniken (AöR) Johannes Wesling Klinikum Minden, Hämatologie/Onkologie, Hämostaseologie und Palliativmedizin
  • Mönchengladbach, Germany, D-41063
    • Krankenhaus Maria Hilf GmbH, Franziskuskrankenhaus, Med. Klinik I
  • Oberhausen, Germany, 46145
    • Praxis für Hämatologie und Internistische Onkologie
  • Offenbach, Germany, 63065
    • Internistisch, Onkologische Gemeinschaftspraxis Dres. Balló
  • Oldenburg, Germany, 26121
    • Onkologische Praxis Oldenburg
  • Regensburg, Germany, 93049
    • Krankenhaus Barmherzige Brüder, Klinik für Onkologie und Hämatologie
  • Reutlingen, Germany, 72764
    • Klinikum am Steinenberg, Ermstalklinik, Medizinische Klinik I
  • Schwäbisch Hall, Germany, 74523
    • Diakonie-Klinikum Schwäbisch Hall gGmbH, Innere Medizin III
  • Siegburg, Germany, D-53721
    • ZAHO-Zentrum für ambulante Hämatologie und Onkologie, Standort Siegburg
  • Siegen, Germany, 57074
    • Diakonie Klinikum Jung-Stilling-Krankenhaus, Medizinische Klinik
  • Singen, Germany, 78224
    • Onkologische Schwerpunktpraxis für Onkologie und Gastroenterologie
  • Speyer, Germany, D-67346
    • Onkologische Schwerpunktpraxis Speyer
  • Trier, Germany, 54290
    • Klinikum Mutterhaus der Borromäerinnen gGmbH
  • Tübingen, Germany, D-72076
    • University Hospital Tübingen, Med. Klinik und Poliklinik, Abt. II
  • Villingen-Schwenningen, Germany, 78052
    • Schwarzwald-Baar Klinikum, Klinik für Innere Medizin II
  • Winnenden, Germany, 71364
    • Rems-Murr-Klinikum gGmbH Winnenden

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients meeting all of the following criteria will be considered for admission to the trial:
• Confirmed diagnosis of untreated multiple myeloma requiring systemic therapy (diagnostic criteria (IMWG updated criteria (2014) )

• Measurable disease, defined as any quantifiable monoclonal protein value, defined by at least one of the following three measurements:

  • Serum M-protein ≥ 10g/l (for IgA ≥ 5g/l)
  • Urine light-chain (M-protein) of ≥ 200 mg/24 hours
  • Serum FLC assay: involved FLC level ≥ 10 mg/dl provided sFLC ratio is abnormal
• Age 18 - 70 years inclusive
• WHO performance status 0-3 (WHO=3 is allowed only if caused by MM and not by co-morbid conditions)
• Negative pregnancy test at inclusion (women of childbearing potential)
• For all men and women of childbearing potential: patients must be willing and capable to use adequate contraception during the complete therapy. Patients must agree on the requirements regarding the lenalidomide pregnancy prevention programme described in chapter 6.

• All patients must

  • agree to abstain from donating blood while taking lenalidomide and for 28 days following discontinuation of lenalidomide therapy
  • agree not to share study drug lenalidomide with another person and to return all unused study drug to the investigator or pharmacist
• Ability of patient to understand character and individual consequences of the clinical trial
• Written informed consent (must be available before enrollment in the trial)

Exclusion Criteria:

• Patients presenting with any of the following criteria will not be included in the trial:
• Patient has known hypersensitivity to any drugs given in the protocol, notably bortezomib, lenalidomide, dexamethasone and elotuzumab or to any of the constituent compounds (incl. boron and mannitol).
• Systemic AL amyloidosis (except for AL amyloidosis of the skin or the bone marrow)
• Previous chemotherapy or radiotherapy during the past 5 years except local radiotherapy in case of local myeloma progression.
• Severe cardiac dysfunction (NYHA classification III-IV)
• Significant hepatic dysfunction (serum bilirubin ≥ 1,8mg/dl and/or ASAT and/or ALAT ≥ 2.5 times normal level), unless related to myeloma.
• Patients with renal insufficiency requiring hemodialysis
• HIV positivity
• Patients with active or history of hepatitis B or C
• Patients with active, uncontrolled infections
• Patients with peripheral neuropathy or neuropathic pain, CTC grade 2 or higher (as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0)
• Patients with a history of active malignancy during the past 5 years with the exception of basal cell carcinoma of the skin or stage 0 cervical carcinoma treated with curative intent
• Patients with acute diffuse infiltrative pulmonary and/or pericardial disease
• Autoimmune hemolytic anemia with positive Coombs test or immune thrombocytopenia
• Platelet count < 75 x 109/l, or, dependent on bone marrow infiltration by plasma cells, platelet count < 30 x 109/l (patients with platelet count < 75 x 109/l, but > 30 x 109/l may be eligible if percentage of plasma cells in bone marrow is ≥ 50%), (transfusion support within 14 days before the test is not allowed)
• Haemoglobin ≤ 8.0 g/dl, unless related to myeloma
• Absolute neutrophil count (ANC) < 1.0 x 10^9/l (the use of colony stimulating factors within 14 days before the test is not allowed), unless related to myeloma
• Pregnancy and lactation
• Participation in other clinical trials. This does not include long-term follow-up periods without active drug treatment of previous studies during the last 6 months.

No patients will be allowed to enrol in this trial more than once.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A1; Induction therapy with 4 cycles VRD (Velcade, Revlimid, Dexamethasone), 21 days per cycle, intensification (mobilization and autologous stem cell transplantation), consolidation therapy with 2 cycles VRD (Velcade, Revlimid, Dexamethasone), 21 days per cycle. Maintenance therapy: 26 cycles (28 days) with lenalidomide (Dexamethasone on day 1 and 15 in cycles 1-6 and on day 1 in cycles 7 to 26).	Drug: Lenalidomide; 25 mg per os on day 1-14 in induction cycle 1-4, 25 mg p.o. on day 1-14 in consolidation cycle 1 and 2, 10 mg p.o. on day 1-28 in maintenance cycle 1-3, 15 mg p.o. on day 1-28 in maintenance cycle 4-26 (all arms); Other Names: Revlimid; Drug: Bortezomib; all arms: 1,3 mg/m^2 subcutaneous on day 1, 4, 8 and 11 in 4 induction cycles, 1,3 mg/m^2 subcutaneous on day 1, 8 and 15 in 2 cycles of consolidation; Other Names: Velcade; Drug: Dexamethasone; 20 mg per os on day 1,2 and 4,5 and 8,9 and 11,12 and 15 in induction cycles 1 and 2. 20 mg per os on day 1,2 and 4,5 and 8,9 and 11,12 in induction cycles 3 and 4 (Arms A1 and A2). 8 mg per os and 12 mg i.v. on day 1, 8 and 15 and 20 mg per os on days 2,4,5, 9, 11 and 12 in induction cycles 1 and 2. 8 mg per os and 12 mg i.v. on day 1, and 11, 20 mg per os on days 2,4,5,8, 9, and 12 in induction cycles 3 and 4 (Arms B1 and B2). 20 mg per os on days 1,2, 8,9, 15 and 16 in both cycles of consolidation (Arms A1 and B1). 8 mg per os and 12 mg i.v. on days 1, 8 and 15 and 20 mg per os on days 2, 9 and 16 in both consolidation cycles (Arms A2 and B2). 12 mg per os on day 1 and 15 in maintenance cycles 1-6, 12 mg per os on day 1 of maintenance cycles 7 and following (Arms A1 and B1). 4 mg per os and 8 mg i.v. on day 1 and 15 in maintenance cycles 1-6, 4 mg per os and 8 mg i.v. on day 1 of maintenance cycles 7 and following (Arms A2 and B2).
Experimental: A2; Induction therapy with 4 cycles VRD (Velcade, Revlimid, Dexamethasone) 21 days per cycle, intensification (mobilization and autologous stem cell transplantation), consolidation therapy with 2 cycles VRD (Velcade, Revlimid, Dexamethasone) + elotuzumab, 21 days per cycle. Maintenance therapy: 26 cycles (28 days) with lenalidomide + elotuzumab (Dexamethasone on day 1 and 15 in cycles 1-6 and on day 1 in cycles 7 to 26).	Drug: Lenalidomide; 25 mg per os on day 1-14 in induction cycle 1-4, 25 mg p.o. on day 1-14 in consolidation cycle 1 and 2, 10 mg p.o. on day 1-28 in maintenance cycle 1-3, 15 mg p.o. on day 1-28 in maintenance cycle 4-26 (all arms); Other Names: Revlimid; Drug: Bortezomib; all arms: 1,3 mg/m^2 subcutaneous on day 1, 4, 8 and 11 in 4 induction cycles, 1,3 mg/m^2 subcutaneous on day 1, 8 and 15 in 2 cycles of consolidation; Other Names: Velcade; Drug: Dexamethasone; 20 mg per os on day 1,2 and 4,5 and 8,9 and 11,12 and 15 in induction cycles 1 and 2. 20 mg per os on day 1,2 and 4,5 and 8,9 and 11,12 in induction cycles 3 and 4 (Arms A1 and A2). 8 mg per os and 12 mg i.v. on day 1, 8 and 15 and 20 mg per os on days 2,4,5, 9, 11 and 12 in induction cycles 1 and 2. 8 mg per os and 12 mg i.v. on day 1, and 11, 20 mg per os on days 2,4,5,8, 9, and 12 in induction cycles 3 and 4 (Arms B1 and B2). 20 mg per os on days 1,2, 8,9, 15 and 16 in both cycles of consolidation (Arms A1 and B1). 8 mg per os and 12 mg i.v. on days 1, 8 and 15 and 20 mg per os on days 2, 9 and 16 in both consolidation cycles (Arms A2 and B2). 12 mg per os on day 1 and 15 in maintenance cycles 1-6, 12 mg per os on day 1 of maintenance cycles 7 and following (Arms A1 and B1). 4 mg per os and 8 mg i.v. on day 1 and 15 in maintenance cycles 1-6, 4 mg per os and 8 mg i.v. on day 1 of maintenance cycles 7 and following (Arms A2 and B2).; Drug: elotuzumab; 10 mg/kg in the vein( i.v) on day 1,8 and 15 in induction cycle 1 and 2, on day 1 and 11 in induction cycle 3 and 4 (Arm B1 and B2). 10 mg/kg i.v. on day 1,8 and 15 in consolidation cycle 1 and 2 (Arm A2 and B2), 10 mg/kg i.v. on day 1 and15 in maintenance cycle 1-6, 10 mg/kg i.v. on day 1 in maintenance cycle 7-26 (Arm A2 and B2)
Experimental: B1; Induction therapy with 4 cycles VRD (Velcade, Revlimid, Dexamethasone) + elotuzumab , 21 days per cycle, intensification (mobilization and autologous stem cell transplantation), consolidation therapy with 2 cycles VRD (Velcade, Revlimid, Dexamethasone) 21 days per cycle. Maintenance therapy: 26 cycles (28 days) with lenalidomide (Dexamethasone on day 1 and 15 in cycles 1-6 and on day 1 in cycles 7 to 26).	Drug: Lenalidomide; 25 mg per os on day 1-14 in induction cycle 1-4, 25 mg p.o. on day 1-14 in consolidation cycle 1 and 2, 10 mg p.o. on day 1-28 in maintenance cycle 1-3, 15 mg p.o. on day 1-28 in maintenance cycle 4-26 (all arms); Other Names: Revlimid; Drug: Bortezomib; all arms: 1,3 mg/m^2 subcutaneous on day 1, 4, 8 and 11 in 4 induction cycles, 1,3 mg/m^2 subcutaneous on day 1, 8 and 15 in 2 cycles of consolidation; Other Names: Velcade; Drug: Dexamethasone; 20 mg per os on day 1,2 and 4,5 and 8,9 and 11,12 and 15 in induction cycles 1 and 2. 20 mg per os on day 1,2 and 4,5 and 8,9 and 11,12 in induction cycles 3 and 4 (Arms A1 and A2). 8 mg per os and 12 mg i.v. on day 1, 8 and 15 and 20 mg per os on days 2,4,5, 9, 11 and 12 in induction cycles 1 and 2. 8 mg per os and 12 mg i.v. on day 1, and 11, 20 mg per os on days 2,4,5,8, 9, and 12 in induction cycles 3 and 4 (Arms B1 and B2). 20 mg per os on days 1,2, 8,9, 15 and 16 in both cycles of consolidation (Arms A1 and B1). 8 mg per os and 12 mg i.v. on days 1, 8 and 15 and 20 mg per os on days 2, 9 and 16 in both consolidation cycles (Arms A2 and B2). 12 mg per os on day 1 and 15 in maintenance cycles 1-6, 12 mg per os on day 1 of maintenance cycles 7 and following (Arms A1 and B1). 4 mg per os and 8 mg i.v. on day 1 and 15 in maintenance cycles 1-6, 4 mg per os and 8 mg i.v. on day 1 of maintenance cycles 7 and following (Arms A2 and B2).; Drug: elotuzumab; 10 mg/kg in the vein( i.v) on day 1,8 and 15 in induction cycle 1 and 2, on day 1 and 11 in induction cycle 3 and 4 (Arm B1 and B2). 10 mg/kg i.v. on day 1,8 and 15 in consolidation cycle 1 and 2 (Arm A2 and B2), 10 mg/kg i.v. on day 1 and15 in maintenance cycle 1-6, 10 mg/kg i.v. on day 1 in maintenance cycle 7-26 (Arm A2 and B2)
Experimental: B2; Induction therapy with 4 cycles VRD (Velcade, Revlimid, Dexamethasone) + elotuzumab, 21 days per cycle, intensification (mobilization and autologous stem cell transplantation), consolidation therapy with 2 cycles VRD (Velcade, Revlimid, Dexamethasone) + elotuzumab, 21 days per cycle. Maintenance therapy: 26 cycles (28 days) with lenalidomide + elotuzumab (Dexamethasone on day 1 and 15 in cycles 1-6 and on day 1 in cycles 7 to 26).	Drug: Lenalidomide; 25 mg per os on day 1-14 in induction cycle 1-4, 25 mg p.o. on day 1-14 in consolidation cycle 1 and 2, 10 mg p.o. on day 1-28 in maintenance cycle 1-3, 15 mg p.o. on day 1-28 in maintenance cycle 4-26 (all arms); Other Names: Revlimid; Drug: Bortezomib; all arms: 1,3 mg/m^2 subcutaneous on day 1, 4, 8 and 11 in 4 induction cycles, 1,3 mg/m^2 subcutaneous on day 1, 8 and 15 in 2 cycles of consolidation; Other Names: Velcade; Drug: Dexamethasone; 20 mg per os on day 1,2 and 4,5 and 8,9 and 11,12 and 15 in induction cycles 1 and 2. 20 mg per os on day 1,2 and 4,5 and 8,9 and 11,12 in induction cycles 3 and 4 (Arms A1 and A2). 8 mg per os and 12 mg i.v. on day 1, 8 and 15 and 20 mg per os on days 2,4,5, 9, 11 and 12 in induction cycles 1 and 2. 8 mg per os and 12 mg i.v. on day 1, and 11, 20 mg per os on days 2,4,5,8, 9, and 12 in induction cycles 3 and 4 (Arms B1 and B2). 20 mg per os on days 1,2, 8,9, 15 and 16 in both cycles of consolidation (Arms A1 and B1). 8 mg per os and 12 mg i.v. on days 1, 8 and 15 and 20 mg per os on days 2, 9 and 16 in both consolidation cycles (Arms A2 and B2). 12 mg per os on day 1 and 15 in maintenance cycles 1-6, 12 mg per os on day 1 of maintenance cycles 7 and following (Arms A1 and B1). 4 mg per os and 8 mg i.v. on day 1 and 15 in maintenance cycles 1-6, 4 mg per os and 8 mg i.v. on day 1 of maintenance cycles 7 and following (Arms A2 and B2).; Drug: elotuzumab; 10 mg/kg in the vein( i.v) on day 1,8 and 15 in induction cycle 1 and 2, on day 1 and 11 in induction cycle 3 and 4 (Arm B1 and B2). 10 mg/kg i.v. on day 1,8 and 15 in consolidation cycle 1 and 2 (Arm A2 and B2), 10 mg/kg i.v. on day 1 and15 in maintenance cycle 1-6, 10 mg/kg i.v. on day 1 in maintenance cycle 7-26 (Arm A2 and B2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the best of four treatment strategies regarding Progression Free Survival (PFS)	response evaluation	time from randomization to progression or death from any cause whichever comes first, censored after two years of maintenance therapy (i.e. approx. after 36 months after randomisation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	survival status	time from randomisation to time of death from any cause. Patients still being alive at the time of the analysis will be censored at the date last known to be alive. (assessed up to 80 months)
complete response rates after induction	response evaluation	approx. after 3 months (after induction therapy)
complete response rates after consolidation	response evaluation	approx. after 9 months (after consolidation therapy)
Progression Free Survival after end of trial	response evaluation	time from randomisation to progression or death from any cause whichever comes first, censored at the end date of the trial (i.e. assessed up to 80 months)
best response to treatment during the study	response evaluation	response assessment after ca. 3 months, 4 months, 7 months, 9 months,11 months, 14 months, and subsequently every 3 months during maintenance treatment, up to 35 months after start of study treatment.
time to progression, censored at end of the trial	Response evaluation	From date of randomization until the date of first documented progression, assessed up to 80 months
duration of response, censored at end of the trial	response evaluation	assessed up to 80 months
toxicity during induction treatment, consolidation and maintenance treatment with respect to adverse Events of CTCAE grade 3 or higher	toxicity according CTCAE Version 4.0	from first administration of study drug until 40 days after last administration of study drug or any drug of the study treatment or upon start of a new subsequent chemotherapy, whichever occurs first
Quality of Life assessment	Questionnaires EORTC-QLQC30 and EORTC-QLQMY20	assessed at baseline, after ca. 3 months, 7 months, 9 months, subsequently every 6 months, up to 36 months

Collaborators and Investigators

• Sponsor: University of Heidelberg Medical Center
• Investigators: Principal Investigator: Hartmut Goldschmidt, Prof. Dr., Med. Klinik V, University Hospital Heidelberg

Publications and helpful links

General Publications

• Salwender H, Bertsch U, Weisel K, Duerig J, Kunz C, Benner A, Blau IW, Raab MS, Hillengass J, Hose D, Huhn S, Hundemer M, Andrulis M, Jauch A, Seidel-Glaetzer A, Lindemann HW, Hensel M, Fronhoffs S, Martens U, Hansen T, Wattad M, Graeven U, Munder M, Fenk R, Haenel M, Scheid C, Goldschmidt H. Rationale and design of the German-speaking myeloma multicenter group (GMMG) trial HD6: a randomized phase III trial on the effect of elotuzumab in VRD induction/consolidation and lenalidomide maintenance in patients with newly diagnosed myeloma. BMC Cancer. 2019 May 28;19(1):504. doi: 10.1186/s12885-019-5600-x.

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): June 24, 2021
• Study Completion (Actual): June 24, 2021

Study Registration Dates

• First Submitted: June 24, 2015
• First Submitted That Met QC Criteria: July 10, 2015
• First Posted (Estimate): July 13, 2015

Study Record Updates

• Last Update Posted (Actual): September 10, 2021
• Last Update Submitted That Met QC Criteria: September 9, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Lenalidomide; Bortezomib; Elotuzumab
• Other Study ID Numbers: GMMG HD6