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

Multiple Myeloma Clinical Trial

— GMMG-HD6  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02495922
• Other study ID #: GMMG HD6
• Status: Completed
• Phase: Phase 3
• Start date: June 2015
• Est. completion date: June 24, 2021

Study information

• Verified date: September 2021
• Source: University of Heidelberg Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 564
• Est. completion date: June 24, 2021
• Est. primary completion date: June 24, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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)
• 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)
• 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
• 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).

Locations

Country	Name	City	State
Germany	Studienzentrum Aschaffenburg	Aschaffenburg
Germany	MVZ Onkologie gGmbH der Klinikum Mittelbaden gGmbH	Baden-Baden
Germany	Charité Campus Benjamin Franklin, III. Med. Abt. (Hämatologie/Onkologie)	Berlin
Germany	HELIOS Klinikum, Klinik für Hämatologie, Onkologie und Immunologie	Berlin
Germany	Onkologisches MVZ Berlin Tegel	Berlin
Germany	Klinikum Bielefeld, Klinik für Hämatologie, Onkologie und Palliativmedizin	Bielefeld
Germany	Studiengesellschaft Onkologie Bielefeld GbR	Bielefeld
Germany	Hämatologisch-onkologische Schwerpunktpraxis	Bochum
Germany	Medizinische Universitätsklinik, Knappschaftskrankenhaus	Bochum
Germany	Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik III, Schwerpunkt Onkologie, Hämatologie und Rheumatologie	Bonn
Germany	ZAHO, Zentrum für ambulante Hämatologie und Onkologie	Bonn
Germany	Schwerpunktpraxis für Onkologie/Hämatologie	Bottrop
Germany	Klinikum Chemnitz GmbH, Innere Medizin III	Chemnitz
Germany	Klinikum Darmstadt, Med. Klinik V, Hämatologie/Onkologie	Darmstadt
Germany	Onkologisches Studienzentrum Darmstadt	Darmstadt
Germany	HELIOS St. Johannes Klinik, Akademisches Krankenhaus der Heinrich-Heine-Universität Düsseldorf	Duisburg
Germany	MVZ Düsseldorf GmbH	Dusseldorf
Germany	Sana Kliniken Düsseldorf GmbH	Düsseldorf
Germany	Universitätsklinikum Düsseldorf, Klinik für Hämatologie,Onkologie und Klin. Immunologie	Düsseldorf
Germany	Universitätsklinik Erlangen	Erlangen
Germany	St.-Antonius-Hospital Klinik f. Hämatologie und Onkologie	Eschweiler
Germany	Ev. Krankenhaus Essen-Werden gGmbH, Zentrum für Innere Medizin, Klinik für Hämatologie, Onkologie und Stammzelltransplantation	Essen
Germany	Universitätsklinikum Essen, Klinik für Hämatologie	Essen
Germany	Centrum für Hämatologie und Onkologie Bethanien	Frankfurt am Main
Germany	Universitätsklinikum Frankfurt, Goethe-Universität Medizinische Klinik II	Frankfurt am Main
Germany	Agaplesion Markus Krankenhaus	Frankfurt/Main
Germany	Praxis und Tagesklinik Friedrichshafen	Friedrichshafen
Germany	Gemeinschaftspraxis Schmitt/Eulenbuch	Gerlingen
Germany	Justus-Liebig-Universität, Medizinische Klinik IV	Gießen
Germany	Kath. Krankenhaus Hagen gGmbH, Abt. Hämatologie/Onkologie	Hagen
Germany	Asklepios Klinik Hamburg Altona, II. Med. Klinik	Hamburg
Germany	Universitätsklinikum Hamburg-Eppendorf, II - Med. Klinik und Poliklinik	Hamburg
Germany	Evangelisches Krankhaus Hamm gGmbH	Hamm
Germany	Onkologische Schwerpunktpraxis	Heidelberg
Germany	University Hospital Heidelberg, Med. Klinik V	Heidelberg
Germany	Onkologische Schwerpunktpraxis	Heilbronn
Germany	SLK Kliniken Heilbronn, Med. Klinik III	Heilbronn
Germany	Universitätsklinikum des Saarlandes, Innere Medizin I	Homburg
Germany	Westpfalz-Klinikum GmbH	Kaiserslautern
Germany	Onkologische Schwerpunktpraxis Karlsruhe	Karlsruhe
Germany	Onkologische Gemeinschaftspraxis Kassel	Kassel
Germany	Praxisklinik für Hämatologie und Onkologie	Koblenz
Germany	Universitätsklinikum Köln, Klinik I - Innere Medizin	Köln
Germany	Onkologisches Zentrum, Gemeinschaftspraxis f. Hämatologie u. Onkologie im Caritas KH	Lebach
Germany	Klinikum Lippe GmbH, Hämatologie-Onkologie	Lemgo
Germany	Schwerpunktpraxis für Hämatologie und Onkologie	Ludwigsburg
Germany	Med. Klinik A, Klinikum der Stadt Ludwigshafen am Rhein gGmbH	Ludwigshafen am Rhein
Germany	Internistische Schwerpunktpraxis für Hämatologie und Onkologie	Mainz
Germany	Universitätsmedizin der Johannes Gutenberg-Universität Mainz, III. Med. Klinik	Mainz
Germany	III. Medizinische Klinik Hämatologie und Internistische Onkologie	Mannheim
Germany	Mannheimer Onkologie Praxis	Mannheim
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	Internistisch, Onkologische Gemeinschaftspraxis Dres. Balló	Offenbach
Germany	Onkologische Praxis Oldenburg	Oldenburg
Germany	Krankenhaus Barmherzige Brüder, Klinik für Onkologie und Hämatologie	Regensburg
Germany	Klinikum am Steinenberg, Ermstalklinik, Medizinische Klinik I	Reutlingen
Germany	Diakonie-Klinikum Schwäbisch Hall gGmbH, Innere Medizin III	Schwäbisch Hall
Germany	ZAHO-Zentrum für ambulante Hämatologie und Onkologie, Standort Siegburg	Siegburg
Germany	Diakonie Klinikum Jung-Stilling-Krankenhaus, Medizinische Klinik	Siegen
Germany	Onkologische Schwerpunktpraxis für Onkologie und Gastroenterologie	Singen
Germany	Onkologische Schwerpunktpraxis Speyer	Speyer
Germany	Klinikum Mutterhaus der Borromäerinnen gGmbH	Trier
Germany	University Hospital Tübingen, Med. Klinik und Poliklinik, Abt. II	Tübingen
Germany	Schwarzwald-Baar Klinikum, Klinik für Innere Medizin II	Villingen-Schwenningen
Germany	Rems-Murr-Klinikum gGmbH Winnenden	Winnenden

Sponsors (1)

Lead Sponsor	Collaborator
University of Heidelberg Medical Center

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	complete response rates after induction	response evaluation	approx. after 3 months (after induction therapy)
Secondary	complete response rates after consolidation	response evaluation	approx. after 9 months (after consolidation therapy)
Secondary	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)
Secondary	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.
Secondary	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
Secondary	duration of response, censored at end of the trial	response evaluation	assessed up to 80 months
Secondary	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
Secondary	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