Compare Lenalidomide and Subcutaneous Daratumumab vs Lenalidomide and Dexamethasone in Frail Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High Dose Therapy

NCT03993912 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: 2018_162018-003535-30
• Study Type: interventional
• Target: 294
• Locations: 1 country
• Sites: 23

Brief Summary

This is a Phase 3, randomized (study drug assigned by chance), open-label (participants and researchers are aware about the treatment, participants are receiving), active-controlled (study in which the experimental treatment or procedure is compared to a standard treatment or procedure), parallel-group (each group of participants will be treated at the same time), and multicenter (when more than one hospital team work on a medical research study) study in participants with newly diagnosed multiple myeloma (a blood cancer of plasma cells) and who are not candidates for high dose chemotherapy (treatment of disease, usually cancer, by chemical agents) and autologous stem cell transplant (ASCT). The primary hypothesis of this study is that subcutaneous Daratumumab in combination with Lenalidomide will prolong progression-free survival and likely induce less toxicity as compared with Lenalidomide and dexamethasone, in elderly frail subjects with newly diagnosed Multiple myeloma who are ineligible for high dose chemotherapy and ASCT

Conditions

Multiple Myeloma

Keywords

Newly diagnosed Multiple Myeloma; Frail elderly patients; Dexamethasone-sparing regimen; Daratumumab; Toxicity

Outcome Measures

Primary Outcomes (1)

• Comparison of the efficacy of Daratumumab SC injection when combined with Lenalidomide (R-Dara SC) vs Lenalidomide and Dexamethasone (Rd): PFS

  The primary objective is to compare the efficacy of Daratumumab SC injection when combined with Lenalidomide (R-Dara SC) to that of Lenalidomide and Dexamethasone (Rd), in terms of PFS in frail subjects with newly diagnosed myeloma who are not candidates for high dose chemotherapy and autologous stem cell transplant.

  From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months

Secondary Outcomes (14)

• Time-to-treatment failure

  From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months

• Time-to-next treatment

  From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months

• PFS2 time

  From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months

• Overall survival (OS) time

  From date of randomization until the date of death from any cause, whichever came first, assessed up to 84months

• Complete remission (CR)

  From date of randomization until the date of first documented progression whichever came first, assessed up to 84months

Study Arms (2)

Arm 1: Experimental group

EXPERIMENTAL

Daratumumab SC 1800 mg * once every week for 8 weeks * then once every other week for 16 weeks * thereafter once every 4 weeks, until progression Lenalidomide PO (25mg): days 1 through 21 of each 28-day cycle, until progression Dexamethasone PO (20mg): days 1, 8, 15, 22 of a 28-day cycle, for the first 2 cycles, then discontinued

Drug: Daratumumab SC in combination with Lenalidomide; Drug: Lenalidomide PO (25mg); Drug: Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression

Arm 2: Control group

SHAM COMPARATOR

Lenalidomide PO (25mg): days 1 through 21 of each 28-day cycle, until progression Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression

Drug: Lenalidomide PO (25mg); Drug: Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression

Interventions

Daratumumab SC in combination with Lenalidomide DRUG

Daratumumab SC 1800 mg * once every week for 8 weeks * then once every other week for 16 weeks * thereafter once every 4 weeks, until progression

Arm 1: Experimental group

Lenalidomide PO (25mg) DRUG

Lenalidomide PO (25mg): days 1 through 21 of each 28-day cycle, until progression

Arm 1: Experimental group; Arm 2: Control group

Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression DRUG

Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression

Arm 1: Experimental group; Arm 2: Control group

Eligibility Criteria

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

You may qualify if:

• Subject must be at least 65 years of age.
• Subject must have documented multiple myeloma satisfying the CRAB criteria and measurable disease.
• Newly diagnosed and not considered candidate for high-dose chemotherapy with SCT.
• Subject must have a Frailty Score ≥ 2
• Subject must have within 5 days prior to first drug intake (C1D1) pretreatment clinical laboratory values meeting the following criteria during the Screening Phase:
• hemoglobin ≥7.5 g/dL
• absolute neutrophil count ≥1.0 x 109/L
• platelet count ≥70 x 109/L
• aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN)
• alanine aminotransferase (ALT) ≤2.5 x ULN
• total bilirubin ≤2.0 x ULN
• creatinine clearance≥30mL/min
• Measurable ISS with β2-microglobulin and albumin values for randomization
• A man who is sexually active with a woman of childbearing potential must agree to use a latex or synthetic condom, even if they had a successful vasectomy. All men must also not donate sperm during the study, for 4 weeks after the last dose of lenalidomide, and for 4 months after the last dose of daratumumab. Women participating in this study must be postmenopausal.
• Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol, as referenced in the ICF.

You may not qualify if:

• Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma.
• Subject has a diagnosis of Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
• Subject has prior or current systemic therapy or SCT for multiple myeloma
• Subject has a history of malignancy (other than multiple myeloma) within 5 years before the date of randomization
• Subject has had radiation therapy within 14 days of randomization.
• Subject has had plasmapheresis within 28 days of randomization.
• Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma.
• Subject has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume \[FEV\] in 1 second \<60% of predicted normal), persistent asthma, or a history of asthma within the last 2 years (intermittent asthma is allowed).
• Subject is known to be seropositive for history of human immunodeficiency virus (HIV)
• Seropositive for hepatitis B.
• (Known to be) seropositive for hepatitis C
• Subject has any concurrent medical or psychiatric condition or disease that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study.
• Subject has clinically significant cardiac disease, including:
• myocardial infarction within 1 year before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function
• uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities

Sponsors & Collaborators

• University Hospital, Lille: lead

Study Sites (23)

Chru Jean Minjoz

Besançon, France

Location

Ch Blois Simone Veil

Blois, France

Location

Ch Fleyriat

Bourg-en-Bresse, France

Location

Chru Brest Site Hopital Morvan

Brest, France

Location

Chu de Caen Normandie

Caen, France

Location

Hopital Prive Sevigne - Cesson

Cesson-Sévigné, France

Location

Chu Dijon Bourgogne

Dijon, France

Location

Chu de Grenoble

Grenoble, France

Location

Gpe Hospitalier La Rochelle-Re-Aunis

La Rochelle, France

Location

Ch Chartres Louis Pasteur-Le Coudray

Le Coudray, France

Location

Hôpital Claude Huriez, CHU

Lille, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Chi Mont de Marsan Et Pays Des Sources

Mont-de-Marsan, France

Location

Chu Montpellier

Montpellier, France

Location

Chu de Nantes Site Hotel Dieu Hme

Nantes, France

Location

Chu de Nice Hopital de L'Archet

Nice, France

Location

Hopital Haut-Leveque - Chu

Pessac, 33604, France

Location

Centre Hospitalier de Perigueux

Périgueux, France

Location

Chru Rennes Site Pontchaillou

Rennes, France

Location

Centre Hospitalier de Saint Quentin

Saint-Quentin, France

Location

Centre Hospitalier Saint-Malo

St-Malo, France

Location

Oncopole Chu Toulouse

Toulouse, France

Location

Chu de Tours

Tours, France

Location

Related Publications (1)

• Manier S, Lambert J, Hulin C, Macro M, Laribi K, Araujo C, Pica GM, Touzeau C, Godmer P, Slama B, Karlin L, Orsini Piocelle F, Dib M, Sanhes L, Morel P, El Yamani A, Tiab M, Tabrizi R, Richez V, Garderet L, Royer B, Bareau B, Mariette C, Fleck E, Robu D, Calmettes C, Rigaudeau S, Demarquette H, Frenzel L, Decaux O, Mohty M, Arnulf B, Bigot N, Perrot A, Corre J, Mary JY, Avet-Loiseau H, Moreau P, Leleu X, Facon T. Safety and efficacy of a dexamethasone-sparing regimen with daratumumab and lenalidomide in patients with frailty and newly diagnosed multiple myeloma (IFM2017-03): a phase 3, open-label, multicentre, randomised, controlled trial. Lancet Oncol. 2025 Oct;26(10):1323-1333. doi: 10.1016/S1470-2045(25)00280-3.

  PMID: 41038184 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide

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)

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

Study Officials

• Thierry Facon, MD,PhD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2019
• First Posted: June 21, 2019
• Study Start: October 17, 2019
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (23)