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

NCT ID: NCT06216158

Last Updated: 2026-02-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

411 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-05

Study Completion Date

2029-06-30

Brief Summary

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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?

Detailed Description

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Prospective, multicentre, randomised, parallel group, open, phase III clinical trial for a maintenance therapy, for patients who underwent an induction therapy and autologous stem cell transplantation (ASCT) in the GMMG-HD8/DSMM XIX trial or a similar quadruplet induction/consolidation therapy regimen followed by at least one ASCT.

Investigational Medicinal Product: Iberdomid (oral), isatuximab (subcutaneous administration via a wearable injector system).

Randomisation will be performed centrally by GMMG/DSMM offices after verification of the eligibility of the patient. At the time of study inclusion, randomization will be performed into arm A (iberdomide) or arm B (iberdomide + isatuximab). Randomization will be stratified by centrally assessed MRD negativity status (yes vs. no vs. unknown); assessed by NGF from BMA; sensitivity of 10\^-5; independent of standard IMWG response) and number of HDM/ASCT (single vs. tandem).

Patients randomized in arm A will receive 39 cycles of the drug iberdomide, a Cereblon E3 Ubiquitin Ligase Modulating Drug (CELMoD®) that shares structural similarities to the immunomodulatory compounds (IMiDs) such as thalidomide and lenalidomide. Each cycle will last for 29 days. Patients in arm B will receive the same the 39 cycles of iberdomide plus monoclonal anti-CD38 antibody isatuximab subcutaneously. In both arms, patients will receive 20 mg dexamethasone in cycle 1, on the same days as the isatuximab administration in Arm B. End of study will be after 36 months of the maintenance therapy.

There is one primary objective:

\- Demonstration of superiority of iberdomide plus isatuximab compared to iberdomide with respect to bone marrow minimal residual disease (MRD) negativity rates (sensitivity 2x10\^-6 via next-generation flow cytometry \[NGF\]) after two years of maintenance therapy.

There is one key secondary objective:

\- PFS, defined as time from randomization to disease progression or death from any cause, whichever occurs first.

Further secondary objectives are:

* Rates of sustained MRD negativity (at sensitivity levels of 10-5 and 2x10\^-6 via NGF from BMA) after 1, 2 and 3 years of maintenance therapy.
* Conversion from MRD positive to negative (at sensitivity levels of 10\^-5 and 2x10\^-6 via NGF from BMA).
* Rates of best overall response to treatment (BOR).
* Rates of partial response (PR), very good partial response (VGPR), complete response (CR) and stringent complete response (sCR).
* Time-to-next-treatment (TTNT).
* PFS on subsequent line of therapy.
* Overall survival (OS).
* Improvement of IMWG response categories (PR, VGPR, CR, sCR).
* Proportions of patients in both treatment arms maintaining BOR and CR from baseline.
* Assessment of quality-of-life (QoL) via the EORTC-QLQC30, EORTC-QLQMY20, and EQ-5D-5L questionnaires.

Conditions

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Multiple Myeloma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm A: Iberdomide

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

Group Type ACTIVE_COMPARATOR

Iberdomide

Intervention Type DRUG

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

Dexamethasone

Intervention Type DRUG

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

Arm B: Iberdomide plus isatuximab

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

Group Type EXPERIMENTAL

Iberdomide

Intervention Type DRUG

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

Isatuximab

Intervention Type DRUG

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

Dexamethasone

Intervention Type DRUG

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

Interventions

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Iberdomide

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

Intervention Type DRUG

Isatuximab

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

Intervention Type DRUG

Dexamethasone

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

Intervention Type DRUG

Other Intervention Names

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Sarclisa

Eligibility Criteria

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Inclusion Criteria

* Prior inclusion and treatment within the GMMG-HD8 / DSMM XIX trial OR
* 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)
* At least Partial Response (PR) according to IMWG criteria at inclusion in the trial
* Age of at least 18 years at trial inclusion
* WHO performance status of 0, 1, or 2
* 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
* Ability of patient to understand character and individual consequences of the clinical trial
* Written informed consent (must be available before enrolment in the trial)

* 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 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. A history of an early stage malignancy during the past 5 years may be acceptable, however, in this case the GMMG study office has to be consulted prior to study inclusion
* 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
* Haemoglobin ≤ 8.0 g/dl, unless related to MM
* Absolute neutrophil count (ANC) \< 1.0 x 109/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)
* Unable or unwilling to undergo thromboprophylaxis
* Pregnancy and lactation
* Participant has any concurrent severe and/or uncontrolled medical condition or psychiatric disease that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study or that confounds the ability to interpret data from the study
* Subjects, who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
* Participation in other interventional clinical trials. This does not include long-term follow-up periods without active drug treatment of previous studies during the last 6 months.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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KKS Netzwerk

NETWORK

Sponsor Role collaborator

Wuerzburg University Hospital

OTHER

Sponsor Role collaborator

Sanofi

INDUSTRY

Sponsor Role collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

University of Heidelberg Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Prof. Dr. Elias Mai

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hartmut Goldschmidt, Prof.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Heidelberg

Locations

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Universitätsklinikum Krems an der Donau

Krems, , Austria

Site Status RECRUITING

Ordensklinikum Linz Elisabethinen

Linz, , Austria

Site Status RECRUITING

Landeskrankenhaus Salzburg, Universitätsklinik für Innere Medizin III

Salzburg, , Austria

Site Status RECRUITING

Klinik Ottakring Wien

Vienna, , Austria

Site Status RECRUITING

Klinikum Wels-Grieskirchen GmbH

Wels, , Austria

Site Status RECRUITING

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

Aachen, , Germany

Site Status RECRUITING

Universitätsklinikum

Augsburg, , Germany

Site Status RECRUITING

Helios Klinikum Bad Saarow

Bad Saarow, , Germany

Site Status RECRUITING

Charité, III. Medizinische Abteilung

Berlin, , Germany

Site Status RECRUITING

Vivantes Klinikum Neukölln, Klinik für Hämatologie und Onkologie

Berlin, , Germany

Site Status RECRUITING

Helios Klinikum Berlin-Buch

Berlin, , Germany

Site Status RECRUITING

Onkologische Schwerpunktpraxis Bielefeld

Bielefeld, , Germany

Site Status RECRUITING

Evangelisches Klinikum Bethel

Bielefeld, , Germany

Site Status RECRUITING

Johanniter Krankenhaus

Bonn, , Germany

Site Status RECRUITING

Universitätsklinikum Bonn

Bonn, , Germany

Site Status RECRUITING

Städtisches Klinikum

Braunschweig, , Germany

Site Status RECRUITING

Klinikum Chemnitz

Chemnitz, , Germany

Site Status RECRUITING

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

Cottbus, , Germany

Site Status RECRUITING

Klinikum Darmstadt GmbH, Medizinische Klinik V

Darmstadt, , Germany

Site Status RECRUITING

Städtisches Klinikum

Dessau, , Germany

Site Status RECRUITING

St. Johannes Hospital Dortmund

Dortmund, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, , Germany

Site Status RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, , Germany

Site Status RECRUITING

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

Düsseldorf, , Germany

Site Status RECRUITING

St. Antonius-Hospital

Eschweiler, , Germany

Site Status RECRUITING

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

Essen, , Germany

Site Status RECRUITING

Malteser Krankenhaus

Flensburg, , Germany

Site Status RECRUITING

Universitätsklinikum Frankfurt

Frankfurt, , Germany

Site Status RECRUITING

Centrum für Hämatologie und Onkologie Bethanien

Frankfurt am Main, , Germany

Site Status RECRUITING

Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

Site Status RECRUITING

Universitätsmedizin Greifswald

Greifswald, , Germany

Site Status RECRUITING

Katholisches Krankenhaus Hagen

Hagen, , Germany

Site Status RECRUITING

Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie

Hamburg, , Germany

Site Status RECRUITING

Asklepios Klinik Altona

Hamburg, , Germany

Site Status RECRUITING

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status RECRUITING

Onkologische Schwerpunktpraxis

Heidelberg, , Germany

Site Status RECRUITING

Universitätsklinikum Heidelberg, Medizinische Klinik V

Heidelberg, , Germany

Site Status RECRUITING

SLK Kliniken Heilbronn, Medizinische Klinik III

Heilbronn, , Germany

Site Status RECRUITING

Universitätsklinikum des Saarlandes, Klinik für Innere Medizin 1

Homburg, , Germany

Site Status RECRUITING

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

Jena, , Germany

Site Status RECRUITING

Westpfalz-Klinikum

Kaiserslautern, , Germany

Site Status RECRUITING

Klinikverbund Allgäu, Klinikum Kempten, Hämatologie / Onkologie

Kempten, , Germany

Site Status RECRUITING

Gemeinschaftsklinikum Mittelrhein Koblenz

Koblenz, , Germany

Site Status RECRUITING

Oncocare, Gemeinschaftspraxis für Hämatologie und Onkologie

Lebach, , Germany

Site Status NOT_YET_RECRUITING

Klinikum der Stadt Ludwigshafen

Ludwigshafen, , Germany

Site Status RECRUITING

Universitätsklinikum Schleswig-Holstein

Lübeck, , Germany

Site Status RECRUITING

Universitätsmedizin der Johannes Gutenberg-Universität

Mainz, , Germany

Site Status RECRUITING

Universitätsklinikum Mannheim, III. Medizinische Klinik

Mannheim, , Germany

Site Status RECRUITING

Onkologie Praxis

Mannheim, , Germany

Site Status RECRUITING

Philipps-Universität Marburg Hämatologie/Onkologie

Marburg, , Germany

Site Status RECRUITING

Klinikum Hochsauerland

Meschede, , Germany

Site Status RECRUITING

Kliniken Maria Hilf

Mönchengladbach, , Germany

Site Status RECRUITING

Kliniken Ostalb

Mutlangen, , Germany

Site Status RECRUITING

Rotkreuzklinikum

München, , Germany

Site Status RECRUITING

Klinikum rechts der Isar der TU München

München, , Germany

Site Status RECRUITING

Klinikum Oldenburg

Oldenburg, , Germany

Site Status RECRUITING

Klinikum Osnabrück GmbH

Osnabrück, , Germany

Site Status RECRUITING

Brüderkrankenhaus St. Josef

Paderborn, , Germany

Site Status RECRUITING

Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie

Regensburg, , Germany

Site Status RECRUITING

Universitätsklinikum Regensburg

Regensburg, , Germany

Site Status RECRUITING

Diakoneo Diak Klinikum

Schwäbisch Hall, , Germany

Site Status RECRUITING

ZAHO - Zentrum für ambulante Hämatologie und Onkologie

Siegburg, , Germany

Site Status RECRUITING

Onkologische Schwerpunktpraxis Speyer

Speyer, , Germany

Site Status RECRUITING

Klinikum der Landeshauptstadt Stuttgart - Katharinenhospital

Stuttgart, , Germany

Site Status RECRUITING

Robert-Bosch-Krankenhaus

Stuttgart, , Germany

Site Status RECRUITING

Universitätsklinikum Tübingen

Tübingen, , Germany

Site Status RECRUITING

Universitätsklinikum

Ulm, , Germany

Site Status RECRUITING

Schwarzwald Baar Klinikum

Villingen-Schwenningen, , Germany

Site Status RECRUITING

University of Würzburg, Med. Klinik und Poliklinik II

Würzburg, , Germany

Site Status RECRUITING

Countries

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Austria Germany

Central Contacts

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Hartmut Goldschmidt, Prof.

Role: CONTACT

+49 6221 568198

Other Identifiers

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GMMG-HD9/DSMM XVIII

Identifier Type: -

Identifier Source: org_study_id

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