Lenalidomide, Bortezomib and Dexamethasone Induction Therapy with Either Intravenous or Subcutaneous Isatuximab in Patients with Newly Diagnosed Multiple Myeloma

NCT ID: NCT05804032

Last Updated: 2025-03-07

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 514 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-14
• Study Completion Date: 2026-07-24

Brief Summary

The trial aims to demonstrate the non-inferiority of subcutaneous to intravenous isatuximab administration in transplant-eligible patients with newly diagnosed multiple myeloma.

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 Product: Isatuximab, subcutaneous administration via a wearable injector system.

Randomization: Patients are randomized in one of 2 study arms (A or B) before induction therapy. Patients randomized in arm A will receive 3 cycles of the monoclonal antibody isatuximab intravenously, combined with RVd regimen (Lenalidomide, Bortezomib, Dexamethasone). Each cycle will last for 42 days. Patients in arm B will receive 3 cycles RVd plus isatuximab subcutaneously. After induction therapy, patients will receive standard intensification (usually cyclophosphamide-based mobilization therapy, stem cell collection and high-dose melphalan followed by autologous stem cell transplantation (HDM/ASCT)). End of study will be after the first HDM/ASCT.

There is one primary objective:

Demonstration of non-inferiority of subcutaneous (SC) isatuximab compared to intravenous (IV) isatuximab, both in combination with RVd, with respect to rates of VGPR or better after induction therapy (according to standard International Myeloma Working Group (IMWG) response criteria).

Key secondary objectives are:

1. Comparison of patient-reported outcomes (PRO) regarding route of administration of isatuximab (SC vs. IV) on induction therapy as assessed by modified CTSQ (modified 9-item questionnaire).

2. Non-inferiority of rates of MRD negativity (assessed by NGS from BMA; sensitivity 10^-5) independent of standard IMWG response after induction therapy.

The duration of the trial for each patients is expected to be approximately 10 months (induction and intensification treatment).

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A - Intravenous isatuximab

Patients in arm A are treated with 3 cycles RVd + i.v. isatuximab, followed by a standard intensification and autologous stem cell transplantation.

Group Type: ACTIVE_COMPARATOR

Isatuximab

Intervention Type: DRUG

IV isatuximab will be administered weekly in the first cycle (Cycle 1) on days 1, 8, 15, 22, 29, and biweekly on the 2 subsequent cycles at days 1, 15 and 29, at the dose of 10 mg/kg.

Lenalidomide

Intervention Type: DRUG

Both arms: 25 mg per os on day 1-14 and d22-35 in induction cycle 1-3

Bortezomib

Intervention Type: DRUG

Both arms: 1.3 mg/m\^2 subcutaneous on day 1, 4, 8, 11, 22, 25, 29 32 in 3 induction cycles

Dexamethasone

Intervention Type: DRUG

20 mg per os on day 1-2, 4-5, 8-9, 11-12, 15; and 22-23, 25-26, 29-30, 32-33 in induction cycles 1-3.

Arm B - Subcutaneous isatuximab

Patients in arm B are treated with 3 cycles RVd + s.c. isatuximab, followed by a standard intensification and autologous stem cell transplantation.

Group Type: EXPERIMENTAL

Isatuximab

Intervention Type: DRUG

SC isatuximab will be administered on days 1, 8, 15, 22, 29 of cycle 1, and on days 1, 15 and 29 of cycles 2-3, at the dose of 1400 mg

Lenalidomide

Intervention Type: DRUG

Both arms: 25 mg per os on day 1-14 and d22-35 in induction cycle 1-3

Bortezomib

Intervention Type: DRUG

Both arms: 1.3 mg/m\^2 subcutaneous on day 1, 4, 8, 11, 22, 25, 29 32 in 3 induction cycles

Dexamethasone

Intervention Type: DRUG

20 mg per os on day 1-2, 4-5, 8-9, 11-12, 15; and 22-23, 25-26, 29-30, 32-33 in induction cycles 1-3.

Interventions

Isatuximab

IV isatuximab will be administered weekly in the first cycle (Cycle 1) on days 1, 8, 15, 22, 29, and biweekly on the 2 subsequent cycles at days 1, 15 and 29, at the dose of 10 mg/kg.

Intervention Type: DRUG

Isatuximab

SC isatuximab will be administered on days 1, 8, 15, 22, 29 of cycle 1, and on days 1, 15 and 29 of cycles 2-3, at the dose of 1400 mg

Intervention Type: DRUG

Lenalidomide

Both arms: 25 mg per os on day 1-14 and d22-35 in induction cycle 1-3

Intervention Type: DRUG

Bortezomib

Both arms: 1.3 mg/m\^2 subcutaneous on day 1, 4, 8, 11, 22, 25, 29 32 in 3 induction cycles

Intervention Type: DRUG

Dexamethasone

20 mg per os on day 1-2, 4-5, 8-9, 11-12, 15; and 22-23, 25-26, 29-30, 32-33 in induction cycles 1-3.

Intervention Type: DRUG

Other Intervention Names

Sarclisa; Sarclisa; Velcade

Eligibility Criteria

Inclusion Criteria

• Confirmed diagnosis of untreated MM requiring systemic therapy (diagnostic criteria according to IMWG)
• Patient is eligible for high-dose melphalan (200 mg/m^2 melphalan) and autologous stem cell transplantation
• Measurable MM disease according to IMWG criteria, defined as any quantifiable monoclonal protein value, defined by at least one of the following three measurements: serum M-protein ≥ 10 g/L; urine light-chain (M-protein) of ≥ 200 mg/24 hours; involved FLC level ≥ 10 mg/dL provided sFLC ratio is abnormal
• Age 18-70 years at trial inclusion

Exclusion Criteria

• Patient has known hypersensitivity (or contraindication) to any of the components of study therapy
• Systemic amyloid light-chain amyloidosis (except for localized AL amyloidosis limited to the skin or the bone marrow)
• Plasma cell leukemia
• Previous chemotherapy or radiotherapy during the past 5 years except local radiotherapy in case of local MM progression
• Severe cardiac dysfunction (NYHA classification III-IV)
• Patients with active or uncontrolled hepatitis B or C or detectable liver disease due to hepatitis B or C
• HIV positivity
• Patients with active, uncontrolled infections
• Patients with severe renal insufficiency or requiring hemodialysis
• Patients with peripheral neuropathy or neuropathic pain, grade 2 or higher (as defined by the NCI Common Terminology Criteria for Adverse Events)
• Patients with a history of any active malignancy during the past 5 years with the exception of following malignancies after curative therapy: basal cell carcinoma of the skin, squamous cell skin carcinoma, stage 0 cervical carcinoma or any in situ malignancy
• Platelet count < 75 x 10^9/L
• Haemoglobin ≤ 8.0 g/dL, unless related to MM
• 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)
• Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L)
• Pregnancy and lactation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Deutsche Studiengruppe Multiples Myelom (DSMM)

UNKNOWN

Sponsor Role: collaborator

KKS Netzwerk

NETWORK

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: collaborator

University of Heidelberg Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Hartmut Goldschmidt

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hartmut Goldschmidt, Prof.

Role: PRINCIPAL_INVESTIGATOR

GMMG study group

Locations

Universitätsklinikum Krems

Krems, , Austria

Ordensklinikum Linz

Linz, , Austria

Landeskrankenhaus Feldkirch-Rankweil

Rankweil, , Austria

Universitätsklinikum der Paracelsus, 3. Med. Abteilung/Onkologie Ambulanz

Salzburg, , Austria

Universitätsklinikum St. Pölten - Lilienfeld

Sankt Pölten, , Austria

Phyrn-Eisenwurzen Klinikum Steyr

Steyr, , Austria

Klinik Ottakring

Vienna, , Austria

Klinikum Wels-Grieskirchen

Wels, , Austria

Uniklinik RWTH Aachen, Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation

Aachen, , Germany

Asklepios Kliniken Hamburg GmbH

Altona, , Germany

Klinikum Augsburg, II. Medizinische Klinik Hämatologie/Onkologie

Augsburg, , Germany

Helios Klinikum Bad Saarow, Klinik für Hämatologie, Onkologie und Palliativmedizin

Bad Saarow, , Germany

MedZentrum Klinikum Bayreuth GmbH

Bayreuth, , Germany

Charité, III. Medizinische Abteilung (Hämatologie/Onkologie)

Berlin, , Germany

Vivantes Klinikum Neukölln, Klinik für Hämatologie und Onkologie

Berlin, , Germany

Klinik für Hämatologie und Stammzelltransplantation, Helios Klinikum Berlin-Buch

Berlin, , Germany

Vivantes Klinikum Spandau

Berlin, , Germany

Bielefeld Praxis, Studiengesellschaft Onkologie

Bielefeld, , Germany

Evangelisches Klinikum Bethel

Bielefeld, , Germany

Johanniter-Krankenhaus Bonn

Bonn, , Germany

Universitätsklinikum Bonn, Medizinische Klinik III

Bonn, , Germany

Städtisches Klinikum Braunschweig

Braunschweig, , Germany

Klinikum Bremen-Mitte

Bremen, , Germany

Klinikum Chemnitz gGmbH

Chemnitz, , Germany

Universitätsklinikum Köln

Cologne, , Germany

Carl-Thiem-Klinikum Cottbus gGmbH, 2. Medizinische Klinik

Cottbus, , Germany

Klinikum Darmstadt, Medizinische Klinik V Hämatologie/Onkologie

Darmstadt, , Germany

Städtisches Klinikum Dessau

Dessau, , Germany

St.-Johannes-Hospital

Dortmund, , Germany

Universitätsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik I

Dresden, , Germany

Helios St. Johannes Klinik Duisburg, Medizinische Klinik 2

Duisburg, , Germany

Universitätsklinikum Düsseldorf, Klinik für Hämatologie, Onkologie und Klinische Immunologie

Düsseldorf, , Germany

Marien Hospital Düsseldorf GmbH, Klinik für Onkologie, Hämatalogie und Palliativmedizin

Düsseldorf, , Germany

St. Antonius-Hospital Eschweiler, Klinik für Hämatologie / Onkologie

Eschweiler, , Germany

Universitätsklinikum Essen

Essen, , Germany

KEM I Evang. Kliniken Essen-Mitte gGmbH, Evangelisches Krankenhaus Essen-Werden gGmbH, Klinik für Hämatologie, Onkologie und Stammzelltransplantation

Essen, , Germany

Malteser Krankenhaus, St. Franziskus Hospital, Hämatologie/Onkologie

Flensburg, , Germany

Centrum für Hämatologie und Onkologie Bethanien

Frankfurt am Main, , Germany

Universitätsklinikum Frankfurt, Medizinische Klinik 2, Hämatologie/Onkologie

Frankfurt am Main, , Germany

Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

Gießen UK

Giessen, , Germany

Universitätsklinikum Göttingen

Göttingen, , Germany

Universitätsmedizin Greifswald, Klinik und Poliklinik für Innere Medizin C

Greifswald, , Germany

Katholisches Krankenhaus Hagen gGmbH, Klinik für Hämatologie und Onkologie

Hagen, , Germany

Universitätsklinikum Halle

Halle, , Germany

Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie

Hamburg, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Onkologische Schwerpunktpraxis Heidelberg

Heidelberg, , Germany

Universitätsklinikum Heidelberg, Medizinische Klinik V

Heidelberg, , Germany

SLK Kliniken Heilbronn, Medizinische Klinik III

Heilbronn, , Germany

Universitätsklinikum des Saarlandes, Klinik für Innere Medizin 1

Homburg, , Germany

Klinikum der Friedrich-Schiller-Universität Jena, Klinik für Innere Medizin II, Abteilung Hämatologie und internistische Onkologie

Jena, , Germany

Westpfalz-Klinikum

Kaiserslautern, , Germany

Städtisches Klinikum Karlsruhe

Karlsruhe, , Germany

Klinikverbund Allgäu, Klinikum Kempten, Hämatologie / Onkologie

Kempten, , Germany

Universitätsklinikum Schleswig-Holstein, Campus Kiel

Kiel, , Germany

Gemeinschaftsklinikum Mittelrhein

Koblenz, , Germany

Gemeinschaftspraxis für Hämatologie und Onkologie

Lebach, , Germany

Universitätsklinikum Leipzig

Leipzig, , Germany

Klinikum der Stadt Ludwigshafen

Ludwigshafen, , Germany

Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Lübeck, , Germany

Universitätsklinikum Magdeburg

Magdeburg, , Germany

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, III. Medizinische Klinik und Poliklinik

Mainz, , Germany

Mannheimer Onkologie Praxis

Mannheim, , Germany

Universitätsklinikum Mannheim, III. Medizinische Klinik

Mannheim, , Germany

Philipps-Universität Marburg, Abteilung Hämatologie, Onkologie und Immunologie am Universitätsklinikum Gießen und Marburg GmbH

Marburg, , Germany

Klinikum Hochsauerland

Meschede, , Germany

Kliniken Maria Hilf GmbH, Medizinische Klinik I

Mönchengladbach, , Germany

Kliniken Ostalb - Standort Stauferklinikum, Hämatologie und Onkologie

Mutlangen, , Germany

Rotkreuzklinikum

München, , Germany

Klinikum rechts der Isar der Technischen Universität München, Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie

München, , Germany

Universitätsklinikum Münster, 1. Medizinische Klinik A

Münster, , Germany

Klinikum Nürnberg

Nuremberg, , Germany

Klinik Oldenburg

Oldenburg, , Germany

Klinikum Osnabrück

Osnabrück, , Germany

Brüderkrankenhaus St. Josef

Paderborn, , Germany

Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie

Regensburg, , Germany

Universitätsklinikum Regensburg

Regensburg, , Germany

CaritasKlinikum Saarbrücken St. Theresia

Saarbrücken, , Germany

Diakonie-Klinikum Schwäbisch Hall gGmbH, Innere Medizin III (Tumorerkrankungen, Palliativmedizin)

Schwäbisch Hall, , Germany

Zentrum für ambulante Hämatologie und Onkologie (ZAHO)

Siegburg, , Germany

Onkologische Schwerpunktpraxis Speyer

Speyer, , Germany

Klinikum der Landeshauptstadt Stuttgart - Katharinenhospital

Stuttgart, , Germany

Diakonie-Klinikum Stuttgart

Stuttgart, , Germany

Robert-Bosch-Krankenhaus

Stuttgart, , Germany

Universität Tübingen, Medizinische Universitätsklinik, Innere Medizin II: Onkologie, Hämatologie, Klinische Immunologie und Rheumatologie

Tübingen, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Schwarzwald-Baar Klinikum

Villingen-Schwenningen, , Germany

Helios Dr. Horst Schmidt Kliniken Wiesbaden GmbH

Wiesbaden, , Germany

Helios Universitätsklinikum Wuppertal

Wuppertal, , Germany

University of Würzburg, Med. Klinik und Poliklinik II

Würzburg, , Germany

Countries

Austria; Germany

Other Identifiers

GMMG-HD8/DSMM XIX

Identifier Type: -

Identifier Source: org_study_id