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

NCT05804032 | Completed Phase 3 DMC

• 1 other identifier: GMMG-HD8/DSMM XIX
• Study Type: interventional
• Target: 514
• Locations: 2 countries
• Sites: 91

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.

Conditions

Multiple Myeloma

Keywords

Neoplasms; Paraproteinemias; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lenalidomide; Bortezomib; Dexamethasone; Isatuximab; Monoclonal antibodies

Outcome Measures

Primary Outcomes (1)

• Demonstration of non-inferiority of subcutaneous (SC) isatuximab compared to intravenous (IV) isatuximab, both in combination with RVd.

  Rates of VGPR or better (according to standard IMWG response criteria), defined as proportion of patients with at least VGPR after induction therapy (according to standard International Myeloma Working Group (IMWG) response criteria).

  18 weeks after start of study treatment

Secondary Outcomes (5)

• Quality of life compared between Arm A and B.

  18 weeks after start of study treatment

• Non-inferiority of rates of MRD negativity in Arm B compared to Arm A

  18 weeks after start of study treatment

• Rates of MRD negativity by NGS and NGF (sensitivity 10^-5, from BMA) independent of standard IMWG response after first HDM/ASCT

  18 weeks (timepoint "after induction") or 35 weeks (timepoint "after first HDM/ASCT") after start of study treatment

• Rates of best overall response to treatment (BOR)

  Depending on the timepoint of best response out of all response assessments, up to 10 months from randomization

• Progression-free survival (PFS)

  Until EOS (28 months after start of study)

Study Arms (2)

Arm A - Intravenous isatuximab

ACTIVE COMPARATOR

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

Drug: Isatuximab; Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone

Arm B - Subcutaneous isatuximab

EXPERIMENTAL

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

Drug: Isatuximab; Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Isatuximab 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.

Also known as: Sarclisa

Arm A - Intravenous isatuximab

Lenalidomide DRUG

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

Arm A - Intravenous isatuximab; Arm B - Subcutaneous isatuximab

Bortezomib DRUG

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

Also known as: Velcade

Arm A - Intravenous isatuximab; Arm B - Subcutaneous isatuximab

Dexamethasone 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 A - Intravenous isatuximab; Arm B - Subcutaneous isatuximab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Heidelberg Medical Center: lead
• Deutsche Studiengruppe Multiples Myelom (DSMM): collaborator
• KKS Netzwerk: collaborator
• Sanofi: collaborator

Study Sites (91)

Universitätsklinikum Krems

Krems, 3500, Austria

Location

Ordensklinikum Linz

Linz, 4020, Austria

Location

Landeskrankenhaus Feldkirch-Rankweil

Rankweil, 6830, Austria

Location

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

Salzburg, 5020, Austria

Location

Universitätsklinikum St. Pölten - Lilienfeld

Sankt Pölten, 3100, Austria

Location

Phyrn-Eisenwurzen Klinikum Steyr

Steyr, 4400, Austria

Location

Klinik Ottakring

Vienna, 1160, Austria

Location

Klinikum Wels-Grieskirchen

Wels, 4600, Austria

Location

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

Aachen, 52074, Germany

Location

Asklepios Kliniken Hamburg GmbH

Altona, 20099, Germany

Location

Klinikum Augsburg, II. Medizinische Klinik Hämatologie/Onkologie

Augsburg, 86156, Germany

Location

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

Bad Saarow, 15526, Germany

Location

MedZentrum Klinikum Bayreuth GmbH

Bayreuth, 95445, Germany

Location

Charité, III. Medizinische Abteilung (Hämatologie/Onkologie)

Berlin, 12200, Germany

Location

Vivantes Klinikum Neukölln, Klinik für Hämatologie und Onkologie

Berlin, 12351, Germany

Location

Klinik für Hämatologie und Stammzelltransplantation, Helios Klinikum Berlin-Buch

Berlin, 13125, Germany

Location

Vivantes Klinikum Spandau

Berlin, 13585, Germany

Location

Bielefeld Praxis, Studiengesellschaft Onkologie

Bielefeld, 33604, Germany

Location

Evangelisches Klinikum Bethel

Bielefeld, 33611, Germany

Location

Johanniter-Krankenhaus Bonn

Bonn, 53113, Germany

Location

Universitätsklinikum Bonn, Medizinische Klinik III

Bonn, 53127, Germany

Location

Städtisches Klinikum Braunschweig

Braunschweig, 38114, Germany

Location

Klinikum Bremen-Mitte

Bremen, 28205, Germany

Location

Klinikum Chemnitz gGmbH

Chemnitz, 09116, Germany

Location

Universitätsklinikum Köln

Cologne, 50937, Germany

Location

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

Cottbus, 03048, Germany

Location

Klinikum Darmstadt, Medizinische Klinik V Hämatologie/Onkologie

Darmstadt, 64283, Germany

Location

Städtisches Klinikum Dessau

Dessau, 06847, Germany

Location

St.-Johannes-Hospital

Dortmund, 44137, Germany

Location

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

Dresden, 01307, Germany

Location

Helios St. Johannes Klinik Duisburg, Medizinische Klinik 2

Duisburg, 47166, Germany

Location

Universitätsklinikum Düsseldorf, Klinik für Hämatologie, Onkologie und Klinische Immunologie

Düsseldorf, 40225, Germany

Location

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

Düsseldorf, 40479, Germany

Location

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

Eschweiler, 52249, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

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

Essen, 45239, Germany

Location

Malteser Krankenhaus, St. Franziskus Hospital, Hämatologie/Onkologie

Flensburg, 24939, Germany

Location

Centrum für Hämatologie und Onkologie Bethanien

Frankfurt am Main, 60389, Germany

Location

Universitätsklinikum Frankfurt, Medizinische Klinik 2, Hämatologie/Onkologie

Frankfurt am Main, 60590, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79110, Germany

Location

Gießen UK

Giessen, 35385, Germany

Location

Universitätsklinikum Göttingen

Göttingen, 37075, Germany

Location

Universitätsmedizin Greifswald, Klinik und Poliklinik für Innere Medizin C

Greifswald, 17475, Germany

Location

Katholisches Krankenhaus Hagen gGmbH, Klinik für Hämatologie und Onkologie

Hagen, 58097, Germany

Location

Universitätsklinikum Halle

Halle, 06120, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Onkologische Schwerpunktpraxis Heidelberg

Heidelberg, 69115, Germany

Location

Universitätsklinikum Heidelberg, Medizinische Klinik V

Heidelberg, 69120, Germany

Location

SLK Kliniken Heilbronn, Medizinische Klinik III

Heilbronn, 74078, Germany

Location

Universitätsklinikum des Saarlandes, Klinik für Innere Medizin 1

Homburg, 66421, Germany

Location

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

Jena, 07740, Germany

Location

Westpfalz-Klinikum

Kaiserslautern, 67655, Germany

Location

Städtisches Klinikum Karlsruhe

Karlsruhe, 76133, Germany

Location

Klinikverbund Allgäu, Klinikum Kempten, Hämatologie / Onkologie

Kempten, 87439, Germany

Location

Universitätsklinikum Schleswig-Holstein, Campus Kiel

Kiel, 24105, Germany

Location

Gemeinschaftsklinikum Mittelrhein

Koblenz, 56073, Germany

Location

Gemeinschaftspraxis für Hämatologie und Onkologie

Lebach, 66822, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Klinikum der Stadt Ludwigshafen

Ludwigshafen, 67063, Germany

Location

Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Lübeck, 23538, Germany

Location

Universitätsklinikum Magdeburg

Magdeburg, 39120, Germany

Location

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

Mainz, 55131, Germany

Location

Mannheimer Onkologie Praxis

Mannheim, 68161, Germany

Location

Universitätsklinikum Mannheim, III. Medizinische Klinik

Mannheim, 68167, Germany

Location

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

Marburg, 35037, Germany

Location

Klinikum Hochsauerland

Meschede, 59870, Germany

Location

Kliniken Maria Hilf GmbH, Medizinische Klinik I

Mönchengladbach, 41063, Germany

Location

Kliniken Ostalb - Standort Stauferklinikum, Hämatologie und Onkologie

Mutlangen, 73557, Germany

Location

Rotkreuzklinikum

München, 80634, Germany

Location

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

München, 81675, Germany

Location

Universitätsklinikum Münster, 1. Medizinische Klinik A

Münster, 48149, Germany

Location

Klinikum Nürnberg

Nuremberg, 90419, Germany

Location

Klinik Oldenburg

Oldenburg, 26133, Germany

Location

Klinikum Osnabrück

Osnabrück, 49076, Germany

Location

Brüderkrankenhaus St. Josef

Paderborn, 33098, Germany

Location

Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie

Regensburg, 93049, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

CaritasKlinikum Saarbrücken St. Theresia

Saarbrücken, 66113, Germany

Location

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

Schwäbisch Hall, 74523, Germany

Location

Zentrum für ambulante Hämatologie und Onkologie (ZAHO)

Siegburg, 53721, Germany

Location

Onkologische Schwerpunktpraxis Speyer

Speyer, 67346, Germany

Location

Klinikum der Landeshauptstadt Stuttgart - Katharinenhospital

Stuttgart, 70174, Germany

Location

Diakonie-Klinikum Stuttgart

Stuttgart, 70176, Germany

Location

Robert-Bosch-Krankenhaus

Stuttgart, 70376, Germany

Location

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

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Schwarzwald-Baar Klinikum

Villingen-Schwenningen, 78052, Germany

Location

Helios Dr. Horst Schmidt Kliniken Wiesbaden GmbH

Wiesbaden, 65199, Germany

Location

Helios Universitätsklinikum Wuppertal

Wuppertal, 42283, Germany

Location

University of Würzburg, Med. Klinik und Poliklinik II

Würzburg, 97080, Germany

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms; Paraproteinemias; Lymphoproliferative Disorders; Immunoproliferative Disorders

Interventions

isatuximab; Lenalidomide; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

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

  GMMG study group

  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: Principal Investigator

Study Record Dates

• First Submitted: March 21, 2023
• First Posted: April 7, 2023
• Study Start: April 14, 2023
• Primary Completion: January 30, 2026
• Study Completion: January 30, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (83); AU (8)