A Phase III Trial on the Effect of Elotuzumab in VRD Induction /Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Myeloma
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT02495922
- Lead Sponsor
- University of Heidelberg Medical Center
- 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
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 564
-
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)
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A1 Lenalidomide 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). A1 Dexamethasone 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). A1 Bortezomib 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). A2 elotuzumab 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). A2 Lenalidomide 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). A2 Bortezomib 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). A2 Dexamethasone 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). B1 elotuzumab 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). B1 Lenalidomide 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). B1 Bortezomib 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). B1 Dexamethasone 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). B2 elotuzumab 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). B2 Lenalidomide 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). B2 Bortezomib 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). B2 Dexamethasone 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).
- Primary Outcome Measures
Name Time Method the best of four treatment strategies regarding Progression Free Survival (PFS) 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) response evaluation
- Secondary Outcome Measures
Name Time Method complete response rates after consolidation approx. after 9 months (after consolidation therapy) response evaluation
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) response evaluation
time to progression, censored at end of the trial From date of randomization until the date of first documented progression, assessed up to 80 months Response evaluation
complete response rates after induction approx. after 3 months (after induction therapy) response evaluation
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. response evaluation
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) survival status
duration of response, censored at end of the trial assessed up to 80 months response evaluation
toxicity during induction treatment, consolidation and maintenance treatment with respect to adverse Events of CTCAE grade 3 or higher 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 toxicity according CTCAE Version 4.0
Quality of Life assessment assessed at baseline, after ca. 3 months, 7 months, 9 months, subsequently every 6 months, up to 36 months Questionnaires EORTC-QLQC30 and EORTC-QLQMY20
Trial Locations
- Locations (67)
Schwarzwald-Baar Klinikum, Klinik für Innere Medizin II
🇩🇪Villingen-Schwenningen, Germany
Rems-Murr-Klinikum gGmbH Winnenden
🇩🇪Winnenden, Germany
Studienzentrum Aschaffenburg
🇩🇪Aschaffenburg, Germany
HELIOS Klinikum, Klinik für Hämatologie, Onkologie und Immunologie
🇩🇪Berlin, Germany
Ev. Krankenhaus Essen-Werden gGmbH, Zentrum für Innere Medizin, Klinik für Hämatologie, Onkologie und Stammzelltransplantation
🇩🇪Essen, Germany
Justus-Liebig-Universität, Medizinische Klinik IV
🇩🇪Gießen, Germany
Schwerpunktpraxis für Hämatologie und Onkologie
🇩🇪Ludwigsburg, Germany
St.-Antonius-Hospital Klinik f. Hämatologie und Onkologie
🇩🇪Eschweiler, Germany
Kath. Krankenhaus Hagen gGmbH, Abt. Hämatologie/Onkologie
🇩🇪Hagen, Germany
SLK Kliniken Heilbronn, Med. Klinik III
🇩🇪Heilbronn, Germany
Westpfalz-Klinikum GmbH
🇩🇪Kaiserslautern, Germany
Onkologische Schwerpunktpraxis Karlsruhe
🇩🇪Karlsruhe, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, III. Med. Klinik
🇩🇪Mainz, Germany
Onkologisches MVZ Berlin Tegel
🇩🇪Berlin, Germany
Charité Campus Benjamin Franklin, III. Med. Abt. (Hämatologie/Onkologie)
🇩🇪Berlin, Germany
Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik III, Schwerpunkt Onkologie, Hämatologie und Rheumatologie
🇩🇪Bonn, Germany
Universitätsklinikum Köln, Klinik I - Innere Medizin
🇩🇪Köln, Germany
Onkologisches Studienzentrum Darmstadt
🇩🇪Darmstadt, Germany
Praxis und Tagesklinik Friedrichshafen
🇩🇪Friedrichshafen, Germany
Gemeinschaftspraxis Schmitt/Eulenbuch
🇩🇪Gerlingen, Germany
Universitätsklinikum Hamburg-Eppendorf, II - Med. Klinik und Poliklinik
🇩🇪Hamburg, Germany
Asklepios Klinik Hamburg Altona, II. Med. Klinik
🇩🇪Hamburg, Germany
University Hospital Heidelberg, Med. Klinik V
🇩🇪Heidelberg, Germany
III. Medizinische Klinik Hämatologie und Internistische Onkologie
🇩🇪Mannheim, Germany
Onkologische Schwerpunktpraxis Speyer
🇩🇪Speyer, Germany
Klinikum Darmstadt, Med. Klinik V, Hämatologie/Onkologie
🇩🇪Darmstadt, Germany
ZAHO, Zentrum für ambulante Hämatologie und Onkologie
🇩🇪Bonn, Germany
Universitätsklinikum Essen, Klinik für Hämatologie
🇩🇪Essen, Germany
Klinikum Bielefeld, Klinik für Hämatologie, Onkologie und Palliativmedizin
🇩🇪Bielefeld, Germany
MVZ Onkologie gGmbH der Klinikum Mittelbaden gGmbH
🇩🇪Baden-Baden, Germany
Studiengesellschaft Onkologie Bielefeld GbR
🇩🇪Bielefeld, Germany
Hämatologisch-onkologische Schwerpunktpraxis
🇩🇪Bochum, Germany
Medizinische Universitätsklinik, Knappschaftskrankenhaus
🇩🇪Bochum, Germany
Schwerpunktpraxis für Onkologie/Hämatologie
🇩🇪Bottrop, Germany
Klinikum Chemnitz GmbH, Innere Medizin III
🇩🇪Chemnitz, Germany
Sana Kliniken Düsseldorf GmbH
🇩🇪Düsseldorf, Germany
HELIOS St. Johannes Klinik, Akademisches Krankenhaus der Heinrich-Heine-Universität Düsseldorf
🇩🇪Duisburg, Germany
Universitätsklinik Erlangen
🇩🇪Erlangen, Germany
MVZ Düsseldorf GmbH
🇩🇪Dusseldorf, Germany
Universitätsklinikum Düsseldorf, Klinik für Hämatologie,Onkologie und Klin. Immunologie
🇩🇪Düsseldorf, Germany
Centrum für Hämatologie und Onkologie Bethanien
🇩🇪Frankfurt am Main, Germany
Agaplesion Markus Krankenhaus
🇩🇪Frankfurt/Main, Germany
Universitätsklinikum Frankfurt, Goethe-Universität Medizinische Klinik II
🇩🇪Frankfurt am Main, Germany
Evangelisches Krankhaus Hamm gGmbH
🇩🇪Hamm, Germany
Onkologische Schwerpunktpraxis
🇩🇪Heilbronn, Germany
Universitätsklinikum des Saarlandes, Innere Medizin I
🇩🇪Homburg, Germany
Onkologische Gemeinschaftspraxis Kassel
🇩🇪Kassel, Germany
Praxisklinik für Hämatologie und Onkologie
🇩🇪Koblenz, Germany
Onkologisches Zentrum, Gemeinschaftspraxis f. Hämatologie u. Onkologie im Caritas KH
🇩🇪Lebach, Germany
Klinikum Lippe GmbH, Hämatologie-Onkologie
🇩🇪Lemgo, Germany
Internistische Schwerpunktpraxis für Hämatologie und Onkologie
🇩🇪Mainz, Germany
Mannheimer Onkologie Praxis
🇩🇪Mannheim, Germany
Med. Klinik A, Klinikum der Stadt Ludwigshafen am Rhein gGmbH
🇩🇪Ludwigshafen am Rhein, Germany
Philipps-Universität Marburg, Hämatologie/Onkologie/Immunologie
🇩🇪Marburg, Germany
Mühlenkreiskliniken (AöR) Johannes Wesling Klinikum Minden, Hämatologie/Onkologie, Hämostaseologie und Palliativmedizin
🇩🇪Minden, Germany
Krankenhaus Maria Hilf GmbH, Franziskuskrankenhaus, Med. Klinik I
🇩🇪Mönchengladbach, Germany
Praxis für Hämatologie und internistische Onkologie
🇩🇪Oberhausen, Germany
Krankenhaus Barmherzige Brüder, Klinik für Onkologie und Hämatologie
🇩🇪Regensburg, Germany
Klinikum am Steinenberg, Ermstalklinik, Medizinische Klinik I
🇩🇪Reutlingen, Germany
Internistisch, Onkologische Gemeinschaftspraxis Dres. Balló
🇩🇪Offenbach, Germany
Onkologische Praxis Oldenburg
🇩🇪Oldenburg, Germany
ZAHO-Zentrum für ambulante Hämatologie und Onkologie, Standort Siegburg
🇩🇪Siegburg, Germany
Diakonie-Klinikum Schwäbisch Hall gGmbH, Innere Medizin III
🇩🇪Schwäbisch Hall, Germany
Onkologische Schwerpunktpraxis für Onkologie und Gastroenterologie
🇩🇪Singen, Germany
Diakonie Klinikum Jung-Stilling-Krankenhaus, Medizinische Klinik
🇩🇪Siegen, Germany
Klinikum Mutterhaus der Borromäerinnen gGmbH
🇩🇪Trier, Germany
University Hospital Tübingen, Med. Klinik und Poliklinik, Abt. II
🇩🇪Tübingen, Germany