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

NCT02495922 | Completed Phase 3 DMC

• 1 other identifier: GMMG HD6
• Study Type: interventional
• Target: 564
• Locations: 1 country
• Sites: 68

Brief Summary

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

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• overall survival

  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

  approx. after 3 months (after induction therapy)

• complete response rates after consolidation

  approx. after 9 months (after consolidation therapy)

• Progression Free Survival after end of trial

  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 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.

Study Arms (4)

A1

ACTIVE COMPARATOR

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; Drug: Bortezomib; Drug: Dexamethasone

A2

EXPERIMENTAL

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: elotuzumab; Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone

B1

EXPERIMENTAL

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: elotuzumab; Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone

B2

EXPERIMENTAL

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: elotuzumab; Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone

Interventions

elotuzumab DRUG

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)

A2; B1; B2

Lenalidomide DRUG

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)

Also known as: Revlimid

A1; A2; B1; B2

Bortezomib DRUG

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

Also known as: Velcade

A1; A2; B1; B2

Dexamethasone DRUG

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).

A1; A2; B1; B2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Heidelberg Medical Center: lead

Study Sites (68)

Studienzentrum Aschaffenburg

Aschaffenburg, 63739, Germany

Location

MVZ Onkologie gGmbH der Klinikum Mittelbaden gGmbH

Baden-Baden, 76532, Germany

Location

HELIOS Klinikum, Klinik für Hämatologie, Onkologie und Immunologie

Berlin, 13125, Germany

Location

Onkologisches MVZ Berlin Tegel

Berlin, 13507, Germany

Location

Charité Campus Benjamin Franklin, III. Med. Abt. (Hämatologie/Onkologie)

Berlin, D-12200, Germany

Location

Klinikum Bielefeld, Klinik für Hämatologie, Onkologie und Palliativmedizin

Bielefeld, D-33604, Germany

Location

Studiengesellschaft Onkologie Bielefeld GbR

Bielefeld, D-33604, Germany

Location

Hämatologisch-onkologische Schwerpunktpraxis

Bochum, 44787, Germany

Location

Medizinische Universitätsklinik, Knappschaftskrankenhaus

Bochum, D-44892, Germany

Location

Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik III, Schwerpunkt Onkologie, Hämatologie und Rheumatologie

Bonn, 53105, Germany

Location

ZAHO, Zentrum für ambulante Hämatologie und Onkologie

Bonn, 53113, Germany

Location

Schwerpunktpraxis für Onkologie/Hämatologie

Bottrop, 46236, Germany

Location

Klinikum Chemnitz GmbH, Innere Medizin III

Chemnitz, D-09116, Germany

Location

Universitätsklinikum Köln, Klinik I - Innere Medizin

Cologne, D-50937, Germany

Location

Onkologisches Studienzentrum Darmstadt

Darmstadt, 64283, Germany

Location

Klinikum Darmstadt, Med. Klinik V, Hämatologie/Onkologie

Darmstadt, D-64283, Germany

Location

HELIOS St. Johannes Klinik, Akademisches Krankenhaus der Heinrich-Heine-Universität Düsseldorf

Duisburg, 47166, Germany

Location

MVZ Düsseldorf GmbH

Düsseldorf, 40235, Germany

Location

Sana Kliniken Düsseldorf GmbH

Düsseldorf, 40593, Germany

Location

Universitätsklinikum Düsseldorf, Klinik für Hämatologie,Onkologie und Klin. Immunologie

Düsseldorf, D-40225, Germany

Location

Universitätsklinik Erlangen

Erlangen, 91054, Germany

Location

St.-Antonius-Hospital Klinik f. Hämatologie und Onkologie

Eschweiler, 52249, Germany

Location

Universitätsklinikum Essen, Klinik für Hämatologie

Essen, D-45147, Germany

Location

Ev. Krankenhaus Essen-Werden gGmbH, Zentrum für Innere Medizin, Klinik für Hämatologie, Onkologie und Stammzelltransplantation

Essen, D-45239, Germany

Location

Centrum für Hämatologie und Onkologie Bethanien

Frankfurt am Main, 60389, Germany

Location

Agaplesion Markus Krankenhaus

Frankfurt am Main, 60431, Germany

Location

Universitätsklinikum Frankfurt, Goethe-Universität Medizinische Klinik II

Frankfurt am Main, 60590, Germany

Location

Praxis und Tagesklinik Friedrichshafen

Friedrichshafen, 88045, Germany

Location

Gemeinschaftspraxis Schmitt/Eulenbuch

Gerlingen, 70839, Germany

Location

Justus-Liebig-Universität, Medizinische Klinik IV

Giessen, 35385, Germany

Location

Kath. Krankenhaus Hagen gGmbH, Abt. Hämatologie/Onkologie

Hagen, D-58095, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, II - Med. Klinik und Poliklinik

Hamburg, D-20246, Germany

Location

Asklepios Klinik Hamburg Altona, II. Med. Klinik

Hamburg, D-22763, Germany

Location

Evangelisches Krankhaus Hamm gGmbH

Hamm, 59063, Germany

Location

Onkologische Schwerpunktpraxis

Heidelberg, 69115, Germany

Location

University Hospital Heidelberg, Med. Klinik V

Heidelberg, D-69120, Germany

Location

Onkologische Schwerpunktpraxis

Heilbronn, 74072, Germany

Location

SLK Kliniken Heilbronn, Med. Klinik III

Heilbronn, D-74078, Germany

Location

Universitätsklinikum des Saarlandes, Innere Medizin I

Homburg, 66421, Germany

Location

Westpfalz-Klinikum GmbH

Kaiserslautern, 67655, Germany

Location

Onkologische Schwerpunktpraxis Karlsruhe

Karlsruhe, 76135, Germany

Location

Onkologische Gemeinschaftspraxis Kassel

Kassel, 34119, Germany

Location

Praxisklinik für Hämatologie und Onkologie

Koblenz, D-56068, Germany

Location

Onkologisches Zentrum, Gemeinschaftspraxis f. Hämatologie u. Onkologie im Caritas KH

Lebach, 66822, Germany

Location

Klinikum Lippe GmbH, Hämatologie-Onkologie

Lemgo, D-32657, Germany

Location

Schwerpunktpraxis für Hämatologie und Onkologie

Ludwigsburg, 71636, Germany

Location

Med. Klinik A, Klinikum der Stadt Ludwigshafen am Rhein gGmbH

Ludwigshafen am Rhein, 67063, Germany

Location

Internistische Schwerpunktpraxis für Hämatologie und Onkologie

Mainz, 55122, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, III. Med. Klinik

Mainz, D-55131, Germany

Location

III. Medizinische Klinik Hämatologie und Internistische Onkologie

Mannheim, 68167, Germany

Location

Mannheimer Onkologie Praxis

Mannheim, D-68161, Germany

Location

Philipps-Universität Marburg, Hämatologie/Onkologie/Immunologie

Marburg, 35032, Germany

Location

Mühlenkreiskliniken (AöR) Johannes Wesling Klinikum Minden, Hämatologie/Onkologie, Hämostaseologie und Palliativmedizin

Minden, 32429, Germany

Location

Krankenhaus Maria Hilf GmbH, Franziskuskrankenhaus, Med. Klinik I

Mönchengladbach, D-41063, Germany

Location

Praxis für Hämatologie und internistische Onkologie

Oberhausen, 46145, Germany

Location

Internistisch, Onkologische Gemeinschaftspraxis Dres. Balló

Offenbach, 63065, Germany

Location

Onkologische Praxis Oldenburg

Oldenburg, 26121, Germany

Location

Krankenhaus Barmherzige Brüder, Klinik für Onkologie und Hämatologie

Regensburg, 93049, Germany

Location

Klinikum am Steinenberg, Ermstalklinik, Medizinische Klinik I

Reutlingen, 72764, Germany

Location

Diakonie-Klinikum Schwäbisch Hall gGmbH, Innere Medizin III

Schwäbisch Hall, 74523, Germany

Location

ZAHO-Zentrum für ambulante Hämatologie und Onkologie, Standort Siegburg

Siegburg, D-53721, Germany

Location

Diakonie Klinikum Jung-Stilling-Krankenhaus, Medizinische Klinik

Siegen, 57074, Germany

Location

Onkologische Schwerpunktpraxis für Onkologie und Gastroenterologie

Singen, 78224, Germany

Location

Onkologische Schwerpunktpraxis Speyer

Speyer, D-67346, Germany

Location

Klinikum Mutterhaus der Borromäerinnen gGmbH

Trier, 54290, Germany

Location

University Hospital Tübingen, Med. Klinik und Poliklinik, Abt. II

Tübingen, D-72076, Germany

Location

Schwarzwald-Baar Klinikum, Klinik für Innere Medizin II

Villingen-Schwenningen, 78052, Germany

Location

Rems-Murr-Klinikum gGmbH Winnenden

Winnenden, 71364, Germany

Location

Related Publications (4)

• Mai EK, Goldschmid H, Miah K, Bertsch U, Besemer B, Hanel M, Krzykalla J, Fenk R, Schlenzka J, Munder M, Durig J, Blau IW, Huhn S, Hose D, Jauch A, Kunz C, Mann C, Weinhold N, Scheid C, Schroers R, von Metzler I, Schieferdecker A, Thomalla J, Reimer P, Mahlberg R, Graeven U, Kremers S, Martens UM, Kunz C, Hensel M, Benner A, Seidel-Glatzer A, Weisel KC, Raab MS, Salwender HJ; German-speaking Myeloma Multicenter Group (GMMG) HD6 investigators. Elotuzumab, lenalidomide, bortezomib, dexamethasone, and autologous haematopoietic stem-cell transplantation for newly diagnosed multiple myeloma (GMMG-HD6): results from a randomised, phase 3 trial. Lancet Haematol. 2024 Feb;11(2):e101-e113. doi: 10.1016/S2352-3026(23)00366-6.

  PMID: 38302221 DERIVED

• Maura F, Rajanna AR, Ziccheddu B, Poos AM, Derkach A, Maclachlan K, Durante M, Diamond B, Papadimitriou M, Davies F, Boyle EM, Walker B, Hultcrantz M, Silva A, Hampton O, Teer JK, Siegel EM, Bolli N, Jackson GH, Kaiser M, Pawlyn C, Cook G, Kazandjian D, Stein C, Chesi M, Bergsagel L, Mai EK, Goldschmidt H, Weisel KC, Fenk R, Raab MS, Van Rhee F, Usmani S, Shain KH, Weinhold N, Morgan G, Landgren O. Genomic Classification and Individualized Prognosis in Multiple Myeloma. J Clin Oncol. 2024 Apr 10;42(11):1229-1240. doi: 10.1200/JCO.23.01277. Epub 2024 Jan 9.

  PMID: 38194610 DERIVED

• Kauer J, Freundt EP, Schmitt A, Weinhold N, Mai EK, Muller-Tidow C, Goldschmidt H, Raab MS, Kriegsmann K, Sauer S. Stem cell collection after lenalidomide, bortezomib and dexamethasone plus elotuzumab or isatuximab in newly diagnosed multiple myeloma patients: a single centre experience from the GMMG-HD6 and -HD7 trials. BMC Cancer. 2023 Nov 21;23(1):1132. doi: 10.1186/s12885-023-11507-9.

  PMID: 37990162 DERIVED

• 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.

  PMID: 31138244 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

elotuzumab; Lenalidomide; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Hartmut Goldschmidt, Prof. Dr.

  Med. Klinik V, University Hospital Heidelberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: June 24, 2015
• First Posted: July 13, 2015
• Study Start: June 1, 2015
• Primary Completion: June 24, 2021
• Study Completion: June 24, 2021
• Last Updated: September 10, 2021

Record last verified: 2021-09

Locations

DE (68)