Iberdomide vs. Iberdomide Plus Isatuximab Maintenance Therapy Post ASCT in Newly Diagnosed Multiple Myeloma

NCT06216158 | Recruiting Phase 3 DMC

• 1 other identifier: GMMG-HD9/DSMM XVIII
• Study Type: interventional
• Target: 411
• Locations: 2 countries
• Sites: 69

Brief Summary

The goal of this clinical trial is to compare a maintenance therapy consisting of iberdomide and isatuximab with an iberdomide-only regimen. The trial is the subsequent maintenance therapy to GMMG-HD8/DSMM XIX trial for patients with newly-diagnosed multiple myeloma. Patients with newly-diagnosed multiple myeloma who underwent a similar quadruplet induction/consolidation therapy regimen followed by at least one ASCT can also be recruited. The main question it aims to answer is: • Will the addition of isatuximab lead to decreased amounts of measurable myeloma cells in the bone marrow after two years?

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Demonstration of superiority of iberdomide plus isatuximab compared to iberdomide with respect to bone marrow minimal residual disease (MRD).

  The primary objective of this trial is to compare the two-year MRD negativity rate (sensitivity 2x10\^-6 via next-generation flow cytometry \[NGF\]; from bone marrow aspirate) when treated with iberdomide plus isatuximab, with the MRD negativity after treatment with iberdomide only.

  24 months after start of maintenance therapy

Secondary Outcomes (1)

• Progression-free survival (PFS) from date of randomization.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Study Arms (2)

Arm A: Iberdomide

ACTIVE COMPARATOR

36 months of oral iberdomide administration; In cycle 1, dexamethasone is added as pre-medication

Drug: Iberdomide; Drug: Dexamethasone

Arm B: Iberdomide plus isatuximab

EXPERIMENTAL

36 months of oral iberdomide plus subcutaneous isatuximab administration; In cycle 1, dexamethasone is added as pre-medication

Drug: Iberdomide; Drug: Isatuximab; Drug: Dexamethasone

Interventions

Iberdomide DRUG

Iberdomide p.o. (0.75 mg, day 1-21 of each 29-days cycle)

Arm A: Iberdomide; Arm B: Iberdomide plus isatuximab

Isatuximab DRUG

Isatuximab s.c. (1400 mg, cycle 1: day 1, 8, 15, 22; cycles 2-3: day 1 and 15; from C4: day 1)

Also known as: Sarclisa

Arm B: Iberdomide plus isatuximab

Dexamethasone DRUG

Dexamethasone p.o. or i.v. (20 mg, cycle 1 only: day 1, 8, 15, 22)

Arm A: Iberdomide; Arm B: Iberdomide plus isatuximab

Eligibility Criteria

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

You may qualify if:

• Received a quadruplet induction/consolidation therapy that consists of a proteasome inhibitor (PI) and immunomodulatory drug (IMiD) \[e.g., bortezomib, thalidomide and dexamethasone, or bortezomib, lenalidomide and dexamethasone\] with an anti-CD38 monoclonal antibody (isatuximab or daratumumab)
• Post HDM/ASCT consolidation containing similar substances as induction therapy is permitted
• Induction and consolidation therapy should make up a total of at least 4 up to 6 cycles, with a maximum of 2 consolidation cycles post HDM/ASCT AND
• Received at least one cycle high dose melphalan therapy (HDM) and autologous stem cell transplantation (ASCT)
• WHO performance status of 0, 1, or 2
• For all men and women of childbearing potential: patients must be willing and capable to use adequate contraception during the complete therapy
• Ability of patient to understand character and individual consequences of the clinical trial
• Written informed consent (must be available before enrolment in the trial)

You may not qualify if:

• Subjects with gastrointestinal disease that may significantly alter the absorption of iberdomide
• Patient has known hypersensitivity (or contraindication) to any of the components of study therapy that are not amenable to premedication with steroids or H1 blockers and that would prohibit further treatment with these agents (e.g. known intolerance or hypersensitivity to infused proteins products, sucrose, histidine, and polysorbate 80 as well as intolerance to arginine and Poloxamer 188)
• Patients with a history of serious allergic reaction to another immunomodulatory agent (thalidomide, lenalidomide, or pomalidomide)", as angioedema and severe dermatologic reactions, including Grade 4 rash and exfoliative or bullous rash
• Patients currently being treated with strong inhibitors or inducers of CYP3A4/5
• Systemic AL amyloidosis (except for localized AL amyloidosis limited to the skin or the bone marrow), plasma cell leukemia or polyneuropathy, organomegaly, endocrinopathy, monoclonal-protein and skin abnormalities or Waldenström macroglobulinemia.
• Severe cardiac dysfunction (NYHA classification III-IV)
• Significant hepatic dysfunction (ASAT and/or ALAT ≥ 3 times normal level and/or serum bilirubin ≥ 1.5 times normal level if not due to hereditary abnormalities as Gilbert's disease), unless related to MM or HDM/ASCT.
• Patients with active or uncontrolled hepatitis B or C or detectable liver disease due to hepatitis B or C. In case of history of hepatitis B or C, it must be clarified whether it has been overcome and negative circulating HBV-DNA or HCV-RNA must be provided. Positive hepatitis B status may only be acceptable in absence of circulating HBV-DNA or signs of chronic or acute infection and if an adequate prophylaxis is being implemented during the course of the study. Prophylaxis for patients with history of hepatitis B or C should be set on a patient individual basis.
• HIV positivity
• Patients with active, uncontrolled infections
• Patients with severe renal insufficiency (Creatinine Clearance \< 30ml/min) 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 (NCI CTCAE, version 5.0)
• Patients with acute diffuse infiltrative pulmonary and/or pericardial disease
• Autoimmune haemolytic anaemia with positive indirect Coombs test or immune thrombocytopenia
• Platelet count \< 75 x 109/l

Sponsors & Collaborators

• Sanofi: collaborator
• University of Heidelberg Medical Center: lead
• KKS Netzwerk: collaborator
• Wuerzburg University Hospital: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (69)

Universitätsklinikum Krems an der Donau

Krems, 3500, Austria

RECRUITING

Ordensklinikum Linz Elisabethinen

Linz, 4020, Austria

RECRUITING

Landeskrankenhaus Salzburg, Universitätsklinik für Innere Medizin III

Salzburg, 5020, Austria

RECRUITING

Klinik Ottakring Wien

Vienna, 1160, Austria

RECRUITING

Klinikum Wels-Grieskirchen GmbH

Wels, 4600, Austria

RECRUITING

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

Aachen, 52074, Germany

RECRUITING

Universitätsklinikum

Augsburg, 86156, Germany

RECRUITING

Helios Klinikum Bad Saarow

Bad Saarow, 15526, Germany

RECRUITING

Charité, III. Medizinische Abteilung

Berlin, 12200, Germany

RECRUITING

Vivantes Klinikum Neukölln, Klinik für Hämatologie und Onkologie

Berlin, 12351, Germany

RECRUITING

Helios Klinikum Berlin-Buch

Berlin, 13125, Germany

RECRUITING

Onkologische Schwerpunktpraxis Bielefeld

Bielefeld, 33604, Germany

RECRUITING

Evangelisches Klinikum Bethel

Bielefeld, 33611, Germany

RECRUITING

Johanniter Krankenhaus

Bonn, 53113, Germany

RECRUITING

Universitätsklinikum Bonn

Bonn, 53127, Germany

RECRUITING

Städtisches Klinikum

Braunschweig, 38114, Germany

RECRUITING

Klinikum Chemnitz

Chemnitz, 09116, Germany

RECRUITING

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

Cottbus, 03048, Germany

RECRUITING

Klinikum Darmstadt GmbH, Medizinische Klinik V

Darmstadt, 64283, Germany

RECRUITING

Städtisches Klinikum

Dessau, 06847, Germany

RECRUITING

St. Johannes Hospital Dortmund

Dortmund, 44137, Germany

NOT YET RECRUITING

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, 01307, Germany

RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

RECRUITING

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

Düsseldorf, 40479, Germany

RECRUITING

St. Antonius-Hospital

Eschweiler, 52249, Germany

RECRUITING

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

Essen, 45239, Germany

RECRUITING

Malteser Krankenhaus

Flensburg, 24939, Germany

RECRUITING

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

RECRUITING

Centrum für Hämatologie und Onkologie Bethanien

Frankfurt am Main, 60389, Germany

RECRUITING

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

RECRUITING

Universitätsmedizin Greifswald

Greifswald, 17475, Germany

RECRUITING

Katholisches Krankenhaus Hagen

Hagen, 58097, Germany

RECRUITING

Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie

Hamburg, 20246, Germany

RECRUITING

Asklepios Klinik Altona

Hamburg, 22763, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, 30625, Germany

RECRUITING

Onkologische Schwerpunktpraxis

Heidelberg, 69115, Germany

RECRUITING

Universitätsklinikum Heidelberg, Medizinische Klinik V

Heidelberg, 69120, Germany

RECRUITING

SLK Kliniken Heilbronn, Medizinische Klinik III

Heilbronn, 74078, Germany

RECRUITING

Universitätsklinikum des Saarlandes, Klinik für Innere Medizin 1

Homburg, 66421, Germany

RECRUITING

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

Jena, 07740, Germany

RECRUITING

Westpfalz-Klinikum

Kaiserslautern, 67655, Germany

RECRUITING

Klinikverbund Allgäu, Klinikum Kempten, Hämatologie / Onkologie

Kempten, 87439, Germany

RECRUITING

Gemeinschaftsklinikum Mittelrhein Koblenz

Koblenz, 56073, Germany

RECRUITING

Oncocare, Gemeinschaftspraxis für Hämatologie und Onkologie

Lebach, 66822, Germany

NOT YET RECRUITING

Klinikum der Stadt Ludwigshafen

Ludwigshafen, 67063, Germany

RECRUITING

Universitätsklinikum Schleswig-Holstein

Lübeck, 23538, Germany

RECRUITING

Universitätsmedizin der Johannes Gutenberg-Universität

Mainz, 55131, Germany

RECRUITING

Universitätsklinikum Mannheim, III. Medizinische Klinik

Mannheim, 68167, Germany

RECRUITING

Onkologie Praxis

Mannheim, 69161, Germany

RECRUITING

Philipps-Universität Marburg Hämatologie/Onkologie

Marburg, 35043, Germany

RECRUITING

Klinikum Hochsauerland

Meschede, 59870, Germany

RECRUITING

Kliniken Maria Hilf

Mönchengladbach, 41063, Germany

RECRUITING

Kliniken Ostalb

Mutlangen, 73557, Germany

RECRUITING

Rotkreuzklinikum

München, 80634, Germany

RECRUITING

Klinikum rechts der Isar der TU München

München, 81675, Germany

RECRUITING

Klinikum Oldenburg

Oldenburg, 26133, Germany

RECRUITING

Klinikum Osnabrück GmbH

Osnabrück, 49076, Germany

RECRUITING

Brüderkrankenhaus St. Josef

Paderborn, 33098, Germany

RECRUITING

Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie

Regensburg, 93049, Germany

RECRUITING

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

RECRUITING

Diakoneo Diak Klinikum

Schwäbisch Hall, 74523, Germany

RECRUITING

ZAHO - Zentrum für ambulante Hämatologie und Onkologie

Siegburg, 53721, Germany

RECRUITING

Onkologische Schwerpunktpraxis Speyer

Speyer, 67346, Germany

RECRUITING

Klinikum der Landeshauptstadt Stuttgart - Katharinenhospital

Stuttgart, 70174, Germany

RECRUITING

Robert-Bosch-Krankenhaus

Stuttgart, 70376, Germany

RECRUITING

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

RECRUITING

Universitätsklinikum

Ulm, 89081, Germany

RECRUITING

Schwarzwald Baar Klinikum

Villingen-Schwenningen, 78052, Germany

RECRUITING

University of Würzburg, Med. Klinik und Poliklinik II

Würzburg, 97080, Germany

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

iberdomide; isatuximab; Dexamethasone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Hartmut Goldschmidt, Prof.

  University Hospital Heidelberg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hartmut Goldschmidt, Prof.

CONTACT

+49 6221 568198; s.gmmg@med.uni-heidelberg.de

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: January 9, 2024
• First Posted: January 22, 2024
• Study Start: April 5, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: February 2, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5); DE (64)