Clinical trial NCT05804032: Lenalidomide, Bortezomib and Dexamethasone Induction Therapy with Either Intravenous or Subcutaneous Isatuximab in Patients with Newly Diagnosed Multiple Myeloma
Official title: A Randomized Phase III Non-inferiority Trial Assessing Lenalidomide, Bortezomib and Dexamethasone Induction Therapy with Either Intravenous or Subcutaneous Isatuximab in Transplant-eligible Patients with Newly Diagnosed Multiple Myeloma.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Neoplasms
Paraproteinemias
Lymphoproliferative Disorders
Immunoproliferative Disorders
Lenalidomide
Bortezomib
Dexamethasone
Isatuximab
Monoclonal antibodies
Lead sponsor: University of Heidelberg Medical Center
Sponsor class: OTHER
Collaborators: name: Deutsche Studiengruppe Multiples Myelom (DSMM)
name: KKS Netzwerk
name: Sanofi
First posted: 2023-04-07
Enrollment: 514
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

For further details on inclusion/exclusion criteria please refer to the study protocol.

Primary outcomes:
measure: Demonstration of non-inferiority of subcutaneous (SC) isatuximab compared to intravenous (IV) isatuximab, both in combination with RVd.
timeFrame: 18 weeks after start of study treatment
Secondary outcomes:
measure: Quality of life compared between Arm A and B.
timeFrame: 18 weeks after start of study treatment
measure: Non-inferiority of rates of MRD negativity in Arm B compared to Arm A
timeFrame: 18 weeks after start of study treatment
measure: Rates of MRD negativity by NGS and NGF (sensitivity 10^-5, from BMA) independent of standard IMWG response after first HDM/ASCT
timeFrame: 18 weeks (timepoint "after induction") or 35 weeks (timepoint "after first HDM/ASCT") after start of study treatment
measure: Rates of best overall response to treatment (BOR)
timeFrame: Depending on the timepoint of best response out of all response assessments, up to 10 months from randomization
measure: Progression-free survival (PFS)
timeFrame: Until EOS (28 months after start of study)
Other outcomes:
Locations:
city: Krems
country: Austria
facility: Universitätsklinikum Krems
city: Linz
country: Austria
facility: Ordensklinikum Linz
city: Rankweil
country: Austria
facility: Landeskrankenhaus Feldkirch-Rankweil
city: Salzburg
country: Austria
facility: Universitätsklinikum der Paracelsus, 3. Med. Abteilung/Onkologie Ambulanz
city: St. Pölten
country: Austria
facility: Universitätsklinikum St. Pölten - Lilienfeld
city: Steyr
country: Austria
facility: Phyrn-Eisenwurzen Klinikum Steyr
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen
city: Wien
country: Austria
facility: Klinik Ottakring
city: Aachen
country: Germany
facility: Uniklinik RWTH Aachen, Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation
city: Augsburg
country: Germany
facility: Klinikum Augsburg, II. Medizinische Klinik Hämatologie/Onkologie
city: Bad Saarow
country: Germany
facility: Helios Klinikum Bad Saarow, Klinik für Hämatologie, Onkologie und Palliativmedizin
city: Bayreuth
country: Germany
facility: MedZentrum Klinikum Bayreuth GmbH
city: Berlin
country: Germany
facility: Charité, III. Medizinische Abteilung (Hämatologie/Onkologie)
city: Berlin
country: Germany
facility: Vivantes Klinikum Neukölln, Klinik für Hämatologie und Onkologie
city: Berlin
country: Germany
facility: Klinik für Hämatologie und Stammzelltransplantation, Helios Klinikum Berlin-Buch
city: Berlin
country: Germany
facility: Vivantes Klinikum Spandau
city: Bielefeld
country: Germany
facility: Bielefeld Praxis, Studiengesellschaft Onkologie
city: Bielefeld
country: Germany
facility: Evangelisches Klinikum Bethel
city: Bonn
country: Germany
facility: Johanniter-Krankenhaus Bonn
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Medizinische Klinik III
city: Braunschweig
country: Germany
facility: Städtisches Klinikum Braunschweig
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Cottbus
country: Germany
facility: Carl-Thiem-Klinikum Cottbus gGmbH, 2. Medizinische Klinik
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt, Medizinische Klinik V Hämatologie/Onkologie
city: Dessau
country: Germany
facility: Städtisches Klinikum Dessau
city: Dortmund
country: Germany
facility: St.-Johannes-Hospital
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik I
city: Duisburg
country: Germany
facility: Helios St. Johannes Klinik Duisburg, Medizinische Klinik 2
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf, Klinik für Hämatologie, Onkologie und Klinische Immunologie
city: Düsseldorf
country: Germany
facility: Marien Hospital Düsseldorf GmbH, Klinik für Onkologie, Hämatalogie und Palliativmedizin
city: Eschweiler
country: Germany
facility: St. Antonius-Hospital Eschweiler, Klinik für Hämatologie / Onkologie
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Essen
country: Germany
facility: KEM I Evang. Kliniken Essen-Mitte gGmbH, Evangelisches Krankenhaus Essen-Werden gGmbH, Klinik für Hämatologie, Onkologie und Stammzelltransplantation
city: Flensburg
country: Germany
facility: Malteser Krankenhaus, St. Franziskus Hospital, Hämatologie/Onkologie
city: Frankfurt am Main
country: Germany
facility: Centrum für Hämatologie und Onkologie Bethanien
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt, Medizinische Klinik 2, Hämatologie/Onkologie
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Gießen
country: Germany
facility: Gießen UK
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald, Klinik und Poliklinik für Innere Medizin C
city: Göttingen
country: Germany
facility: Universitätsklinikum Göttingen
city: Hagen
country: Germany
facility: Katholisches Krankenhaus Hagen gGmbH, Klinik für Hämatologie und Onkologie
city: Halle
country: Germany
facility: Universitätsklinikum Halle
city: Hamburg-Altona
country: Germany
facility: Asklepios Kliniken Hamburg GmbH
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Onkologische Schwerpunktpraxis Heidelberg
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg, Medizinische Klinik V
city: Heilbronn
country: Germany
facility: SLK Kliniken Heilbronn, Medizinische Klinik III
city: Homburg
country: Germany
facility: Universitätsklinikum des Saarlandes, Klinik für Innere Medizin 1
city: Jena
country: Germany
facility: Klinikum der Friedrich-Schiller-Universität Jena, Klinik für Innere Medizin II, Abteilung Hämatologie und internistische Onkologie
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum
city: Karlsruhe
country: Germany
facility: Städtisches Klinikum Karlsruhe
city: Kempten
country: Germany
facility: Klinikverbund Allgäu, Klinikum Kempten, Hämatologie / Onkologie
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Kiel
city: Koblenz
country: Germany
facility: Gemeinschaftsklinikum Mittelrhein
city: Köln
country: Germany
facility: Universitätsklinikum Köln
city: Lebach
country: Germany
facility: Gemeinschaftspraxis für Hämatologie und Onkologie
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Ludwigshafen
country: Germany
facility: Klinikum der Stadt Ludwigshafen
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Lübeck
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz, III. Medizinische Klinik und Poliklinik
city: Mannheim
country: Germany
facility: Mannheimer Onkologie Praxis
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim, III. Medizinische Klinik
city: Marburg
country: Germany
facility: Philipps-Universität Marburg, Abteilung Hämatologie, Onkologie und Immunologie am Universitätsklinikum Gießen und Marburg GmbH
city: Meschede
country: Germany
facility: Klinikum Hochsauerland
city: Mutlangen
country: Germany
facility: Kliniken Ostalb - Standort Stauferklinikum, Hämatologie und Onkologie
city: Mönchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH, Medizinische Klinik I
city: München
country: Germany
facility: Rotkreuzklinikum
city: München
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München, Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie
city: Münster
country: Germany
facility: Universitätsklinikum Münster, 1. Medizinische Klinik A
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg
city: Oldenburg
country: Germany
facility: Klinik Oldenburg
city: Osnabrück
country: Germany
facility: Klinikum Osnabrück
city: Paderborn
country: Germany
facility: Brüderkrankenhaus St. Josef
city: Regensburg
country: Germany
facility: Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
city: Saarbrücken
country: Germany
facility: CaritasKlinikum Saarbrücken St. Theresia
city: Schwäbisch Hall
country: Germany
facility: Diakonie-Klinikum Schwäbisch Hall gGmbH, Innere Medizin III (Tumorerkrankungen, Palliativmedizin)
city: Siegburg
country: Germany
facility: Zentrum für ambulante Hämatologie und Onkologie (ZAHO)
city: Speyer
country: Germany
facility: Onkologische Schwerpunktpraxis Speyer
city: Stuttgart
country: Germany
facility: Klinikum der Landeshauptstadt Stuttgart - Katharinenhospital
city: Stuttgart
country: Germany
facility: Diakonie-Klinikum Stuttgart
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
city: Tübingen
country: Germany
facility: Universität Tübingen, Medizinische Universitätsklinik, Innere Medizin II: Onkologie, Hämatologie, Klinische Immunologie und Rheumatologie
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Villingen-Schwenningen
country: Germany
facility: Schwarzwald-Baar Klinikum
city: Wiesbaden
country: Germany
facility: Helios Dr. Horst Schmidt Kliniken Wiesbaden GmbH
city: Wuppertal
country: Germany
facility: Helios Universitätsklinikum Wuppertal
city: Würzburg
country: Germany
facility: University of Würzburg, Med. Klinik und Poliklinik II
Study officials:
affiliation: GMMG study group
name: Hartmut Goldschmidt, Prof.
role: PRINCIPAL_INVESTIGATOR
References: