JOURNAL ONKOLOGIE – STUDIE

Isatuximab in Combination With Rd Compared to Rd in Elderly Patients (Aged ≥70 Years) With NDMM

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

Rekrutierend

NCT-Nummer:
NCT04891809

Studienbeginn:
Oktober 2021

Letztes Update:
22.11.2023

Wirkstoff:
Isatuximab-Irfc 20 MG/ML [Sarclisa], Lenalidomide, Dexamethasone Oral

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

Geschlecht:
Alle

Altersgruppe:
Senioren (66+)

Phase:
Phase 2

Sponsor:
Arbeitsgemeinschaft medikamentoese Tumortherapie

Collaborator:
University of Navarra, Medical University of Vienna, Assign Data Management and Biostatistics GmbH, WiSP GmbH, Sanofi,

Studienleiter

Heinz Ludwig
Principal Investigator
Wilhelminen Cancer Research Institute, Clinic Ottakring

Kontakt

Daniela Wolkersdorfer
Kontakt:
Phone: +43 662640
Phone (ext.): 4412
E-Mail: d.wolkersdorfer@agmt.at» Kontaktdaten anzeigen

Studienlocations
(3 von 23)

Univ.-Klinik für Innere Medizin V Innsbruck, Abteilung für Hämatologie und Onkologie
6020 Innsbruck
AustriaZurückgezogen» Google-Maps

Med.Univ.Graz, Univ.-Klinikum f. Innere Medizin, Klin. Abt. f. Haematologie
8036 Graz
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Siegfried Sormann, OA, MD
Phone: +43 316 385
Phone (ext.): 81814
E-Mail: Siegfried.Sormann@klinikum-graz.at

Julia Lodron, MSc. BScN.
Phone: +43 316 385
Phone (ext.): 31188
E-Mail: julia.lodron@medunigraz.at» Ansprechpartner anzeigen

Klinik Klagenfurt am Wörthersee Abteilung für Innere Medizin und Hämatologie und internistische Onkologie
9020 Klagenfurt
AustriaNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Joachim Rettl, Senior MD
Phone: +43 463 538
Phone (ext.): 25119
E-Mail: joachim.rettl@kabeg.at

Melanie Lang, DGKP
Phone: +43 463 538
Phone (ext.): 28670
E-Mail: melanie.lang@kabeg.at» Ansprechpartner anzeigen

Bezirkskrankenhaus Kufstein, Innere Medizin, Interne II u. onkologische Tagesklinik
6330 Kufstein
AustriaRekrutierend» Google-Maps
Ansprechpartner:
August Zabernigg, Head MD PD
Phone: +43 5372 6966
Phone (ext.): 3001
E-Mail: august.zabernigg@bkh-kufstein.at

Sabine Kriesche
E-Mail: sabine.kriesche@bkh-kufstein.at» Ansprechpartner anzeigen

LKH Hochsteiermark - Leoben, Abt. f. Innere Medizin, Haemato-Onkologie
8700 Leoben
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Thamer Sliwa, MD, DL
Phone: +43 3842 401
Phone (ext.): 2821
E-Mail: thamer.sliwa@kages.at

Manuela Maderdonner, BSc.,MSc.
Phone: +43 3842 401
Phone (ext.): 3402
E-Mail: manuela.maderdonner@kages.at» Ansprechpartner anzeigen

JKU Linz, Univ.-Klinik f. Hämatologie und Internistische Onkologie, MC III.
4021 Linz
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Clemens Schmitt, Prof. MD
E-Mail: clemens.schmitt@kepleruniklinikum.at

Isabella Rauscher, MSc
Phone: +43 5 7680 83
Phone (ext.): 6204
E-Mail: isabella.rauscher@kepleruniklinikum.at» Ansprechpartner anzeigen

Univ.Klinikum Krems, Klin. Abt. f. Innere Medizin 2
3500 Mitterweng
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Klaus Podar, MD, PhD
Phone: +43 2732 9004
Phone (ext.): 22324
E-Mail: klaus.podar@krems.lknoe.at

Elisabeth Zwickl-Traxler, Mag.
E-Mail: studienzentrale@krems.lknoe.at» Ansprechpartner anzeigen

LKH Feldkirch, Innere Medizin II, Interne E: Hämatologie und Onkologie
6830 Rankweil
AustriaNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Bernd Hartmann, MD
Phone: +43 5522 303
Phone (ext.): 2681
E-Mail: bernd.hartmann@lkhf.at» Ansprechpartner anzeigen

PMU Salzburg: Universitätsklinik für Innere Medizin III
5020 Salzburg
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Richard Greil, Head Prof MD
Phone: +43 57255
Phone (ext.): 25800
E-Mail: r.greil@salk.at

Michaela Schachner
E-Mail: m.schachner@salk.at» Ansprechpartner anzeigen

Univ.-Klinikum St. Pölten, Innere Medizin 1
3100 St.Pölten
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Petra Pichler, MD
Phone: +43 2742 9004
Phone (ext.): 22181
E-Mail: petra.pichler@stpoelten.lknoe.at» Ansprechpartner anzeigen

Krankenhaus d. Barmh. Schwestern Wien, 1. Med. Abteilung, Onkologie und Hämatologie
1060 Vienna
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Eva M. Autzinger, MD
Phone: +43 1 599 88
E-Mail: evamaria.autzinger@bhs.at» Ansprechpartner anzeigen

AKH Meduni Wien Universitätsklinik für Innere Medizin I: Klinische Abteilung für Hämatologie und Hämostaseologie
1090 Vienna
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Maria-Theresa Krauth, Prof.PD MD
Phone: +43 1 40400
Phone (ext.): 44100
E-Mail: maria.krauth@meduniwien.ac.at

Phone: +43 1 40160
Phone (ext.): 57551
E-Mail: renate.schoder@meduniwien.ac.at» Ansprechpartner anzeigen

Klinik Hietzing, 5. Medizinische Abteilung
1130 Vienna
AustriaNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Daniel Lechner-Radner, Senior MD
Phone: +43 1 80110
Phone (ext.): 2239
E-Mail: hietzing.forschung@gmail.com

Elmir Graf, Mag.Pharm
Phone: +43 699 119 43 524
E-Mail: hietzing.forschung@gmail.com» Ansprechpartner anzeigen

Klinik Ottakring, 1.Med.Abt., Zentrum f. Onkologie, Haematologie und Palliativmedizin
1160 Vienna
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Martin Schreder, MD
Phone: +43 1 491 50
Phone (ext.): 2151
E-Mail: martin.schreder@gesundheitsverbund.at» Ansprechpartner anzeigen

Hanusch Krankenhaus der Österreichischen Gesundheitskasse, 3. Med. Abteilung
1140 Wien
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Michael Fillitz, MD
Phone: +43191021
Phone (ext.): 85500
E-Mail: michael.fillitz@oegk.at

Barbara Dixer, BSc
Phone: +43191021
Phone (ext.): 85435
E-Mail: barbara.dixer@oegk.at» Ansprechpartner anzeigen

Krankenhaus Zams, Innere Medizin, Internistische Onkologie-Haematologie
6511 Zams
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Ewald Wöll, Prof. MD
Phone: +43 5442 600
Phone (ext.): 7421
E-Mail: ewald.woell@krankenhaus-zams.at

Carmen Ruepp
Phone: +43 664 600 85
Phone (ext.): 5971
E-Mail: carmen.ruepp@krankenhaus-zams.at» Ansprechpartner anzeigen

General Hospital of Athens "Evangelismos", Hematology Clinic
10676 Athens
GreeceRekrutierend» Google-Maps
Ansprechpartner:
Sosana Delimpasi, MD
Phone: +30 6977204193
E-Mail: sodeli@yahoo.com

George Nakis
Phone: +30 6944822722
E-Mail: giorgosnakis@yahoo.gr» Ansprechpartner anzeigen

General Hospital of Athens "Alexandra, Plasma Cell Dyscrasias Unit
11528 Athens
GreeceRekrutierend» Google-Maps
Ansprechpartner:
Evangelos Terpos, Prof.MD
Phone: +30 2132162846
E-Mail: eterpos@hotmail.com

Natasha Stavri
Phone: +30 6985640810
E-Mail: natashastavri23@gmail.com» Ansprechpartner anzeigen

Anticancer Hospital of Thessaloniki "Theageneio", Hematology
54639 Thessaloníki
GreeceRekrutierend» Google-Maps
Ansprechpartner:
Eirini Katodrytou, MD,Dir.
Phone: +30 6974 872869
E-Mail: eirinikatodritou@gmail.com

Evdoxia Kallia
Phone: +30 6944186629
E-Mail: kalliaevi@gmail.com» Ansprechpartner anzeigen

University Clinical Center of Serbia, Clinic for Hematology
11000 Belgrade
SerbiaRekrutierend» Google-Maps
Ansprechpartner:
Jelena Bila, MD, Prof
Phone: +38 1638292992
E-Mail: biladr.jelena@gmail.com

Goran Tadic
Phone: +381642410370
E-Mail: goran.tadic81@yahoo.com» Ansprechpartner anzeigen

University Clinical Center Kragujevac, Clinic for Hematology
34000 Kragujevac
SerbiaNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Predrag Djurdjevic, MD, Prof.
Phone: +381641663402
E-Mail: pdjurdjevic@sbb.rs

Violeta Trajkovic
Phone: +381655342776
E-Mail: vikidunja1234@gmail.com» Ansprechpartner anzeigen

University Clinical Center Nis, Clinic for Hematology
18000 Niš
SerbiaNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Miodrag Vucic, MD, Prof.
Phone: +38 163405600
E-Mail: buca.vucic@gmail.com

Aleksandra Cosic
Phone: +381605290292
E-Mail: alexdaki92@gmail.com» Ansprechpartner anzeigen

Clinical center of Vojvodina, Clinic for Hematology
21000 Novi Sad
SerbiaNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Ivana Urosevic, MD, PhD
Phone: +38169747557
E-Mail: ivana.urosevic@mf.uns.ac.rs

Bosa Sikic
Phone: +381668552477
E-Mail: bosa.sikic@gmail.com» Ansprechpartner anzeigen

Alle anzeigen

Studien-Informationen

Detailed Description:

The treatment goals in elderly patients with multiple myeloma (MM) are similar to those in

younger patients: rapid and long-lasting symptom control, deep response and durable

remissions as well as increased survival are at the forefront, similar to therapy goals in

younger patients. Elderly patients frequently present with comorbidities, reduced treatment

tolerance and greater frequency of treatment discontinuations. Hence, treatment needs to be

adapted to the specific needs of this patient population.

ln the recent decade lenalidomide-based therapies have been established as effective

treatment modalities in elderly patients. In elderly patients lenalidomide + dexamethasone

(Rd) is one of the most frequently used treatment regimens, which is effective and well

tolerated.

MM is a high unmet medical need and as a result, several agents are currently under clinical

investigation in MM. Monoclonal antibodies (mAb) are one of the most promising groups of

drugs in development in the treatment of MM with several of them demonstrating activity in

this disease. lsatuximab is a highly effective monoclonal antibody with an excellent activity

and tolerance profile, active as single agent therapy in patients with multiple prior lines

of treatment.

Presently several trials with isatuximab-lenalidomide containing treatment regimens are

ongoing. The expected benefits of adding isatuximab to Rd over Rd alone in very elderly

patients seem to outweigh possible risks by far.

A greater depth of response is anticipated including greater number of MRD (minimal residual

disease) negative patients, higher response rates, and longer progression free survival.

Risk conferred with the addition of isatuximab are mainly restricted to a roughly 40% rate of

infusion reactions, which usually are seen at the first infusion only. ln addition, there is

an increased risk for grade 4 leukopenia, grade 2 and 3 thrombocytopenia, and grade 3

infection and fatigue.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Age ≥ 70 years

- Able to provide written informed consent in accordance with federal, local, and

institutional guidelines

- Patients must have newly diagnosed, symptomatic multiple myeloma with evidence of

measurable disease (assessed within 21 days prior to randomization)

- Serum M protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis

and/or

- Urine M protein ≥200 mg/24 hours measured using urine protein

immunoelectrophoresis and/or

- In subjects without detectable serum or urine M-protein, serum-free light chain

(SFLC) ≥100 mg/L (involved light chain) and an abnormal FLC ratio

- No prior treatment for multiple myeloma

- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2

- Patients at cardiac risk (NYHA >ll) or pre-existing coronary heart disease, or any

other clinically relevant cardiac complication) should be scheduled for a baseline

ECHO and can only be included if the LVEF is >40%

- Adequate organ and bone marrow function within the 21 days prior to randomization

defined by:

- Bilirubin < 2 times the upper limit of normal (ULN), Aspartate aminotransferase

(AST) and alanine aminotransferase (ALT) < 3 times the ULN

- absolute neutrophil count (ANC) ≥ 750/mm3 (growth factor support for max 3 days

allowed to achieve this value)

- Hemoglobin >8.0 g/dL (Use of erythropoietic stimulating factors and red blood

cell [RBC] transfusion per institutional guidelines is allowed, however the most

recent RBC transfusion may not have been done within 7 days prior to obtaining

screening hemoglobin.)

- Platelet count >50,000/mm3

- Calculated or measured creatinine clearance (CrCl) of ≥30 mL/min; Calculation

should be based on the MDRD formula (age, gender, black/non- black, weight,

height)

Exclusion Criteria:

- ECOG status >2

- Patients unlikely to tolerate Rd

- Waldenström macroglobulinemia

- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and

skin changes)

- Plasma cell leukemia (> 2.0 x 10^9/L circulating plasma cells by standard

differential)

- Myelodysplastic syndrome

- Smoldering Myeloma and MGUS

- Second malignancy within the past 5 years except:

- Adequately treated basal cell or squamous cell skin cancer

- Carcinoma in situ of the cervix

- Prostate cancer ≤ Gleason score 6 with stable prostate-specific antigen (PSA over

12 months)

- Ductal breast carcinoma in situ with full surgical resection (i.e., negative

margins)

- Treated medullary or papillary thyroid cancer

- History of or current amyloidosis

- Glucocorticoid therapy within the 14 days prior to randomization that exceeds an

accumulated dose of 160 mg dexamethasone or 1000 mg prednisone

- Extended field radio therapy (more than 3 fields) within the 21 days prior to

randomization

- Contraindication to isatuximab, dexamethasone, lenalidomide or any of the required

concomitant drugs or supportive treatments, including hypersensitivity to antiviral

drugs

- Active congestive heart failure (New York Heart Association [NYHA] Class III or IV),

symptomatic ischemia, conduction abnormalities uncontrolled by conventional

intervention, acute diffuse infiltrative pulmonary disease, pericardial disease, or

myocardial infarction within 4 months prior to enrolment

- Active infection within the 14 days prior to randomization requiring systemic

antibiotics and/or antiviral therapy

- Uncontrolled hypertension or uncontrolled diabetes despite medication

- Significant neuropathy (Grade 2 with pain or Grade 3 or higher) within the 14 days

prior to randomization

- Known cirrhosis

- Known human immunodeficiency virus (HIV) seropositivity or active hepatitis C or

hepatitis B infection (subjects with past hepatitis B virus [HBV] infection or

resolved HBV infection defined as having a negative HBsAg test and a positive antibody

to hepatitis B core antigen [anti HBc] antibody test are eligible; subjects positive

for hepatitis C virus [HCV] antibody are eligible only if polymerase chain reaction

[PCR] is negative for HCV RNA.)

- Participation in another interventional study within the 28 days prior to

randomization

- Major surgery (except kyphoplasty) within the 28 days prior to randomization

- Any other clinically significant medical disease or social condition that, in the

Investigator's opinion, may interfere with protocol adherence or a subject's ability

to give informed consent, be compliant with study procedures, or provide accurate

information.

Studien-Rationale

Primary outcome:

1. Proportion of patients with MRD (minimal residual disease) negativity (defined by NGF [next generation flow] at 10^-5) after end of induction treatment in the two arms. (Time Frame - After 8 months of induction treatment (8 cycles, each cyle is 28 days)):
To demonstrate the benefit of isatuximab in combination with lenalidomide and low-dose dexamethasone followed by isatuximab and lenalidomide maintenance therapy in changing the proportion of patients with MRD negativity as compared to lenalidomide and low-dose dexamethasone followed by lenalidomide maintenance treatment in patients with newly diagnosed multiple myeloma (NDMM).

Secondary outcome:

1. Percentage of patients with response to study treatment (Time Frame - After 32 months (8 months of induction treatment and a maximum of 24 months of maintenance treatment)):
Effect of treatment on Overall Response Rate (ORR) including patients with Partial Response (PR), Very Good Partial Response (VGPR) and Complete Response (CR) as per International Myeloma Working Group (IMWG) criteria in each arm.

2. Progression-free Survival (Time Frame - After 44 months (8 months of induction treatment and a maximum of 24 months of maintenance treatment and a minimum of 12 months of follow-up)):
Effectiveness of treatments on Progression-free survival (PFS)

3. Overall Survival (Time Frame - After 44 months (8 months of induction treatment and a maximum of 24 months of maintenance treatment and a minimum of 12 months of follow-up)):
Effectiveness of treatments on Overall Survival (OS)

4. Effectiveness of treatments on MRD negativity (Time Frame - After 20 months (8 months of induction treatment and 12 months of maintenance treatemnent)):
To evaluate the proportion of patients with MRD negativity (defined by NGF [next generation flow] at 10^-5) after 12 months (13 cycles) of maintenance treatment.

5. Effectiveness of treatments on preventing progressive disease (Time Frame - After 44 months (8 months of induction treatment and a maximum of 24 months of maintenance treatment and a minimum of 12 months of follow-up)):
To evaluate the Time to Progression (TTP) in each arm.

6. Progression-free Survival in different high-risk cytogenetic populations (Time Frame - After 44 months (8 months of induction treatment and a maximum of 24 months of maintenance treatment and a minimum of 12 months of follow-up)):
Effectiveness of treatment on PFS in high risk cytogenetic populations defined as patients carrying a) del(17p), t(4;14), t(14;16) in each arm and b) the same aberrations plus amp1q21.

7. Duration of response (Time Frame - After 44 months (8 months of induction treatment and a maximum of 24 months of maintenance treatment and a minimum of 12 months of follow-up)):
Length of time between response and progression or death.

8. Incidence of treatment-emergent adverse events (Safety and tolerability) (Time Frame - After 32 months (8 months of induction treatment and a maximum of 24 months of maintenance treatment)):
Number of participants with treatment-emergent adverse events as assessed by NCI-CTCAE Version 5.0.

9. Changes in quality of life (QoL) using general questionnaire European Organization for Research and Treatment of Cancer (EORTC) Quality of life questionnaire (QLQ) Core 30 (C 30) (EORTC-QLQ-C30) (Time Frame - After 32 months (8 months of induction treatment and a maximum of 24 months of maintenance treatment)):
Changes in quality of life will be analyzed by using the cancer patient-specific questionnaire EORTC-QLQ-C30.

10. Changes of general health status using questionnaire EQ (EuroQol) 5 dimension (5D) 5 level (5L) (EQ-5D-5L) (Time Frame - After 32 months (8 months of induction treatment and a maximum of 24 months of maintenance treatment)):
Changes in general health status will be analyzed by using the questionnaires EQ-5D-5L. QoL.

11. Changes in quality of life (QoL) using multiple myeloma specific questionnaire EORTC-QLQ Myeloma (MY) 20 (EORTC-QLQ-MY20) (Time Frame - After 32 months (8 months of induction treatment and a maximum of 24 months of maintenance treatment)):
Changes in quality of life will be analyzed by using the multiple myeloma-specific questionnaire EORTC-QLQ-MY20.

12. Progression-free survival after second line therapy (Time Frame - After end of study treatment until 12 months of follow up as a minimum (until LPLV)):
Influence of potential second line therapy on Progression-free Survival

Studien-Arme

Experimental: IRd followed by IR
Induction: 8 cycles isatuximab+lenalidomide+dexamethasone; Maintenance: up to 24 cylces isatuximab+lenalidomide
Other: Rd followed by R
Induction: 8 cycles lenalidomide+dexamethasone; Maintenance: up to 24 cylces lenalidomide

Geprüfte Regime

Isatuximab-Irfc 20 MG/ML [Sarclisa]:
Induction: 10mg/kg on day 1,8,15,22 in cycle 1, subsequently on day 1, 15; every 28 days (q28 days) Maintenance: 10mg/kg, day1, q28 days until progression or intolerance but for a maximum of 24 cycles from start of maintenance
Lenalidomide:
Induction: 25mg*, day 1-21, every 28 days (q28 days); Maintenance: 5-10mg, day 1-21, q28 days (according to individual tolerance) until progression or intolerance but for a maximum of 24 cycles from start of maintenance *) for patients with moderate renal impairment (30≤ GFR (MDRD formula) < 50 mL/min) starting dose is 10 mg
Dexamethasone Oral:
Induction: Patients aged <75 years: 40mg, once weekly; Patients aged ≥75 years: 20mg, once weekly

Quelle: ClinicalTrials.gov

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"Isatuximab in Combination With Rd Compared to Rd in Elderly Patients (Aged ≥70 Years) With NDMM"

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