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

NCT04891809 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: AGMT_MM-4
• Study Type: interventional
• Target: 198
• Locations: 3 countries
• Sites: 14

Brief Summary

As optimal tolerance is the key for developing new treatments for the very elderly population, the aim of the study is to compare the efficacy and tolerance of isatuximab in combination with lenalidomide+dexamethasone (Rd) versus Rd only in very elderly patients aged 70 years or older. ln sum, a clear and clinically highly relevant benefit is expected with the isatuximab-based triple combination compared to the standard Rd doublet.

Conditions

Newly Diagnosed Multiple Myeloma

Keywords

Myeloma; Isatuximab; Lenalidomide; Dexamethasone; Elderly; age ≥70

Outcome Measures

Primary Outcomes (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.

  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).

  After 8 months of induction treatment (8 cycles, each cyle is 28 days)

Secondary Outcomes (12)

• Percentage of patients with response to study treatment

  After 32 months (8 months of induction treatment and a maximum of 24 months of maintenance treatment)

• Progression-free Survival

  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)

• Overall Survival

  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 MRD negativity

  After 20 months (8 months of induction treatment and 12 months of maintenance treatemnent)

• Effectiveness of treatments on preventing progressive disease

  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)

Study Arms (2)

IRd followed by IR

EXPERIMENTAL

Induction: 8 cycles isatuximab+lenalidomide+dexamethasone; Maintenance: up to 24 cylces isatuximab+lenalidomide

Drug: Isatuximab-Irfc 20 MG/ML [Sarclisa]; Drug: Lenalidomide; Drug: Dexamethasone Oral

Rd followed by R

OTHER

Induction: 8 cycles lenalidomide+dexamethasone; Maintenance: up to 24 cylces lenalidomide

Drug: Lenalidomide; Drug: Dexamethasone Oral

Interventions

Isatuximab-Irfc 20 MG/ML [Sarclisa] DRUG

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

IRd followed by IR

Lenalidomide DRUG

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

IRd followed by IR; Rd followed by R

Dexamethasone Oral DRUG

Induction: Patients aged \<75 years: 40mg, once weekly; Patients aged ≥75 years: 20mg, once weekly

IRd followed by IR; Rd followed by R

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• Other tumors with low risk of recurrence/metastases and/or early stage R0 surgery
• History of or current amyloidosis

Sponsors & Collaborators

• Arbeitsgemeinschaft medikamentoese Tumortherapie: lead
• University of Navarra: collaborator
• Medical University of Vienna: collaborator
• Assign Data Management and Biostatistics GmbH: collaborator
• WiSP GmbH: collaborator
• Sanofi: collaborator

Study Sites (14)

Bezirkskrankenhaus Kufstein, Innere Medizin, Interne II u. onkologische Tagesklinik

Kufstein, 6330, Austria

Location

LKH Hochsteiermark - Leoben, Abt. f. Innere Medizin, Haemato-Onkologie

Leoben, 8700, Austria

Location

Univ.Klinikum Krems, Klin. Abt. f. Innere Medizin 2

Mitterweng, 3500, Austria

Location

PMU Salzburg: Universitätsklinik für Innere Medizin III

Salzburg, 5020, Austria

Location

Univ.-Klinikum St. Pölten, Innere Medizin 1

Sankt Pölten, 3100, Austria

Location

Krankenhaus d. Barmh. Schwestern Wien, 1. Med. Abteilung, Onkologie und Hämatologie

Vienna, 1060, Austria

Location

Hanusch Krankenhaus der Österreichischen Gesundheitskasse, 3. Med. Abteilung

Vienna, 1140, Austria

Location

Klinik Ottakring, 1.Med.Abt., Zentrum f. Onkologie, Haematologie und Palliativmedizin

Vienna, 1160, Austria

Location

Krankenhaus Zams, Innere Medizin, Internistische Onkologie-Haematologie

Zams, 6511, Austria

Location

General Hospital of Athens "Evangelismos", Hematology Clinic

Athens, 10676, Greece

Location

General Hospital of Athens "Alexandra, Plasma Cell Dyscrasias Unit

Athens, 11528, Greece

Location

Anticancer Hospital of Thessaloniki "Theageneio", Hematology

Thessaloniki, 54639, Greece

Location

University Clinical Center of Serbia, Clinic for Hematology

Belgrade, 11000, Serbia

Location

University Clinical Center Kragujevac, Clinic for Hematology

Kragujevac, 34000, Serbia

Location

Related Publications (1)

• Facon T, Dimopoulos MA, Meuleman N, Belch A, Mohty M, Chen WM, Kim K, Zamagni E, Rodriguez-Otero P, Renwick W, Rose C, Tempescul A, Boyle E, Manier S, Attal M, Moreau P, Macro M, Leleu X, Lorraine Chretien M, Ludwig H, Guo S, Sturniolo M, Tinel A, Silvia Monzini M, Costa B, Houck V, Hulin C, Yves Mary J. A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial. Leukemia. 2020 Jan;34(1):224-233. doi: 10.1038/s41375-019-0539-0. Epub 2019 Aug 19.

  PMID: 31427722 BACKGROUND

Related Links

• Sponsor

MeSH Terms

Conditions

Neoplasms, Plasma Cell

Interventions

isatuximab; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Heinz Ludwig

  Wilhelminen Cancer Research Institute, Clinic Ottakring

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomly assigned in a 1:1 ratio to one of the two arms. Randomization will be stratified by the simplified frailty scale (Facon et al, Leukemia 2020) result nonfrail or frail.

Study Record Dates

• First Submitted: May 12, 2021
• First Posted: May 18, 2021
• Study Start: October 20, 2021
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (9); GR (3); SE (2)