JOURNAL ONKOLOGIE – STUDIE

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

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT06216158

Studienbeginn:
April 2024

Letztes Update:
10.04.2024

Wirkstoff:
Iberdomide, Isatuximab, Dexamethasone

Indikation (Clinical Trials):
Multiple Myeloma, Neoplasms, Plasma Cell

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
University of Heidelberg Medical Center

Collaborator:
KKS Netzwerk, Wuerzburg University Hospital, Sanofi, Bristol-Myers Squibb,

Studienleiter

Hartmut Goldschmidt, Prof.
Principal Investigator
University Hospital Heidelberg

Kontakt

Hartmut Goldschmidt, Prof.
Kontakt:
Phone: +49 6221 568198
E-Mail: s.gmmg@med.uni-heidelberg.de» Kontaktdaten anzeigen

Studienlocations
(3 von 17)

Uniklinik RWTH Aachen, Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation
52074 Aachen
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Vivantes Klinikum Neukölln, Klinik für Hämatologie und Onkologie
12351 Berlin
(Berlin)
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Universitätsklinikum Bonn, Medizinische Klinik III
53127 Bonn
(Nordrhein-Westfalen)
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Carl-Thiem-Klinikum Cottbus gGmbH, 2. Medizinische Klinik
03048 Cottbus
(Brandenburg)
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Klinikum Darmstadt GmbH, Medizinische Klinik V
64283 Darmstadt
(Hessen)
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Marien Hospital Düsseldorf GmbH, Klinik für Onkologie, Hämatalogie und Palliativmedizin
40479 Düsseldorf
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps

KEM I Evang. Kliniken Essen-Mitte gGmbH, Evangelisches Krankenhaus Essen-Werden gGmbH, Klinik für Hämatologie, Onkologie und Stammzelltransplantation
45239 Essen
(Nordrhein-Westfalen)
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Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie
20246 Hamburg
(Hamburg)
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Universitätsklinikum Heidelberg, Medizinische Klinik V
69120 Heidelberg
(Baden-Württemberg)
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SLK Kliniken Heilbronn, Medizinische Klinik III
74078 Heilbronn
(Baden-Württemberg)
GermanyNoch nicht rekrutierend» Google-Maps

Universitätsklinikum des Saarlandes, Klinik für Innere Medizin 1
66421 Homburg
(Saarland)
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Klinikum der Friedrich-Schiller-Universität Jena, Klinik für Innere Medizin II, Abteilung Hämatologie und internistische Onkologie
07740 Jena
(Thüringen)
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Klinikverbund Allgäu, Klinikum Kempten, Hämatologie / Onkologie
87439 Kempten
(Bayern)
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Universitätsklinikum Mannheim, III. Medizinische Klinik
68167 Mannheim
(Baden-Württemberg)
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Darmkrebszentrum im Brüderkrankenhaus St. Josef Paderborn
Husener Straße 46
33098 Paderborn
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Krankenhaus Barmherzige Brüder Regensburg, Klinik für Onkologie und Hämatologie
93049 Regensburg
(Bayern)
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University of Würzburg, Med. Klinik und Poliklinik II
97080 Würzburg
(Bayern)
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Alle anzeigen

Studien-Informationen

Detailed Description:

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 in the GMMG-HD8/DSMM XIX trial.

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.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Prior inclusion and treatment within the GMMG-HD8 / DSMM XIX trial

- 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)

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.

- Previous systemic anti-myeloma treatment other than administered within the GMMG-HD8 /

DSMM XIX trial (including up to two cycles cycle high dose melphalan therapy (HDM) and

autologous stem cell transplantation (ASCT). Local, consolidative radiotherapy for

myeloma disease is permitted unless performed in case of progressive disease according

to IMWG criteria

- 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.

Studien-Rationale

Primary outcome:

1. Demonstration of superiority of iberdomide plus isatuximab compared to iberdomide with respect to bone marrow minimal residual disease (MRD). (Time Frame - 24 months after start of maintenance therapy):
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.

Secondary outcome:

1. Progression-free survival (PFS) from date of randomization. (Time Frame - 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):
PFS, defined as time from randomization to disease progression or death from any cause, whichever occurs first.

Studien-Arme

Active Comparator: Arm A: Iberdomide
36 months of oral iberdomide administration; In cycle 1, dexamethasone is added as pre-medication
Experimental: Arm B: Iberdomide plus isatuximab
36 months of oral iberdomide plus subcutaneous isatuximab administration; In cycle 1, dexamethasone is added as pre-medication

Geprüfte Regime

Iberdomide:
Iberdomide p.o. (1.0 mg, day 1-21 of each 29-days cycle)
Isatuximab (Sarclisa):
Isatuximab s.c. (1400 mg, cycle 1: day 1, 8, 15, 22; cycles 2-3: day 1 and 15; from C4: day 1)
Dexamethasone:
Dexamethasone p.o. or i.v. (20 mg, cycle 1 only: day 1, 8, 15, 22)

Quelle: ClinicalTrials.gov

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