Elranatamab/Lenalidomide Consolidation and/or Elranatamab Maintenance Versus Standard of Care After D-VRd Induction in Transplant-eligible NDMM Patients
ElLen
A Phase 3, Open-label, Controlled, Randomized Study of Newly Diagnosed Multiple Myeloma Treatment, Designed to Evaluate the Efficacy and Safety of the Elranatamab-lenalidomide Combination as a Replacement for Chemotherapy Followed by Autologous Stem Cell Transplant in the Consolidation Phase, and to Compare Elranatamab With Standard of Care in the Maintenance Phase
2 other identifiers
interventional
824
1 country
64
Brief Summary
This study is designed as a multicenter, randomized, parallel groups, open-label, phase 3 study in subjects with untreated newly diagnoses Multiple Myeloma eligible for ASCT. 824 patients will be enrolled in this study from approximately 70 study sites. The 2 parts in the Treatment Phase are described below. Part 1: Induction/ASCT/Consolidation Phase (1:1 Randomization) After the screening period, patients will be randomly allocated (1:1) to either:
- Arm A (standard of care arm): standard induction therapy with 4 cycles of D-VRd, followed by HDCT (Melphalan) + ASCT, D-VRd consolidation therapy
- Arm B (experimental arm): standard induction therapy with 4 cycles of D-VRd, followed by elranatamab and lenalidomide consolidation therapy. Part 2: Maintenance Phase (1:1 Re-randomization) Patients will be re-randomized (1:1) and will enter the Maintenance Phase upon completion of consolidation therapy.
- Arm C (standard of care arm): lenalidomide
- Arm D (experimental arm): elranatamab
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jul 2025
Longer than P75 for phase_3
64 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 10, 2024
CompletedFirst Posted
Study publicly available on registry
April 9, 2025
CompletedStudy Start
First participant enrolled
July 9, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2036
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 1, 2036
April 2, 2026
July 1, 2025
10.8 years
December 10, 2024
March 28, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
Part 1 (induction/consolidation) from Randomization 1 (R1): to assess whether consolidation therapy with elranatamab and lenalidomide is superior to standard of care, in terms of Minimal Residual Disease (MRD) negativity rate
To assess whether consolidation therapy with elranatamab and lenalidomide is superior to standard of care, in terms of MRD negativity rate.
at end of consolidation, up to 36 months
Part 2 (maintenance) from Randomization 2 (R2): to assess whether maintenance therapy with elranatamab is superior to standard of care, in terms of Progression Free Survival (PFS).
To assess whether maintenance therapy with elranatamab is superior to standard of care, in terms of PFS.
from the date of second randomization to the date of confirmed PD (IMWG criteria,) or death from any cause, whichever came first, assessed up to 93 monts
Key secondary objectives: Part 1 (induction/consolidation) from R1: to assess whether consolidation therapy with elranatamab and lenalidomide is superior, in terms of PFS
To assess whether consolidation therapy with elranatamab and lenalidomide is superior, in terms of PFS
PFS defined as the time interval from the date of first randomization to the date of confirmed Progression Disease (IMWG criteria) or death from any cause, whichever occurs first., assessed up to 128 months
Key secondary objectives: Part I (induction/consolidation) from R1: to assess whether consolidation therapy with elranatamab and lenalidomide is superior to standard of care, in terms of Overal Survival (OS)
To assess whether consolidation therapy with elranatamab and lenalidomide is superior to standard of care, in terms of OS
up to 128 months
Secondary Outcomes (8)
Part 1 (induction/consolidation) from R1: to assess the efficacy of consolidation therapy with elranatamab and lenalidomide compared to standard of care
End of consolidation phase, up to 36 months
Part 2 (maintenance) from R2: to assess the efficacy of maintenance therapy with elranatamab
end of maintenance, up to 58 months
assess safety & Tolerability during induction, and during consolidation and maintenance therapy: Adverse events (AE), serious Adrverse events (SAE) and And adverse events of special interest (AESI) rates - Incidence of Treatment-Emergent Adverse Events
through study completion, up to 128 months
Throughout the study to evaluate the impact of treatment on health-related Quality of Life (QoL) using Rework questionnaire
through study completion, up to 128 months
Part 2 (maintenance) from Randomization 2 (R2): to assess the efficacy of maintenance therapy with elranatamab, Progression Free Survival 2 form Randomization 2
up to 128 months
- +3 more secondary outcomes
Other Outcomes (5)
EXPLORATORY OBJECTIVES: to assess the impact of genomic markers (from Next generation sequencing (NGS) and Whole Genome Sequencing (WGS)) on outcome
up to 128 months
EXPLORATORY OBJECTIVES: to assess Immune mechanisms predicting Elra-Len vs ASCT efficacy
up to 128 months
EXPLORATORY OBJECTIVES: to assess the impact of PET imaging parameters/variables on outcome
End of consolidation phase, up to 36 months
- +2 more other outcomes
Study Arms (4)
D-VRD induction, ASCT and D-VRD consolidation (arm A)
ACTIVE COMPARATORStandard induction therapy with 4 cycles of D-VRd, followed by HDCT (Melphalan) + ASCT, and 2 cycles of D-VRd consolidation therapy
D-VRD induction followed by elranatamab and lenalidomide consolidation (arm B)
EXPERIMENTALStandard induction therapy with 4 cycles of D-VRd, followed by elranatamab and lenalidomide consolidation therapy.
lenalidomide maintenance (Arm C)
ACTIVE COMPARATORLenalidomide monotherapy for two years (maintenance)
elranatamab maintenance (Arm D)
EXPERIMENTALElranatamab monotherapy for two years (maintenance)
Interventions
Elranatamab is given to arm B patients in association with lenalidomide (for consolidation) and arm D patients in monotherapy (for maintenance) as experimental arms
In association with daratumumab, bortezomib and dexamethasone (Arm A), in association with elranatamab (Arm B), in monotherapy (Arm C)
Daratumumab is given in association with bortezomib, lenalidomide and dexamethasone in induction therapy (all patients) and consolidation arm A
ASCT is performed in consolidation for Arm A patients after induction therapy with D-VRD
Bortezomib is given in associtaion with daratumumab, lenalidomide and dexamethasone in induction (all patients) and consolidation Arm A
Dexamethasone is given in association with daratumumab, bortezomib and lenalidomide in induction (all patients) and consolidation Arm A
Eligibility Criteria
You may qualify if:
- Male or female subjects, aged over 18.
- Patients have provided voluntary written informed consent before performing any study-related procedure.
- Patients with newly diagnosed multiple myeloma (NDMM) eligible for high-dose chemotherapy (melphalan) and autologous stem cell transplantation (ASCT).
- Patients with documented symptomatic NDMM according to CRAB and/or SLIM criteria, with measurable disease as defined by:
- Presence of ≥10% monoclonal plasma cells in the bone marrow OR presence of a biopsy-proven plasmacytoma. In addition, the patient must have ≥1 of the following myeloma defining events:
- \- Hypercalcemia: serum calcium \>0.25 mmol/L (\>1 mg/dL) higher than upper limits of normal (ULN) or \>2.75 mmol/L (\>11 mg/dL).
- \- Renal insufficiency: creatinine clearance \< 40mL/min/1.73 m2 using CKD-EPI or serum creatinine \>177 μmol/L (\>2 mg/dL).
- \- Anemia: hemoglobin \>2 g/dL below the lower limit of normal (LLN) or hemoglobin \<10 g/dL.
- Bone lesions: ≥1 osteolytic lesion on skeletal radiography, CT or PET-CT.
- Clonal bone marrow plasma cell percentage ≥60%.
- Serum involved/uninvolved free light chain ratio ≥100.
- More than 1 focal lesion (≥5 mm diameter) on MRI.
- Measurable disease as defined by serum M-component ≥5 g/L, and/or urine M-component ≥200 mg/24 h and/or serum FLC ≥100 mg/L.
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2.
- Patients must have clinical laboratory values (within 15 days of initiating induction therapy) as follows:
- +9 more criteria
You may not qualify if:
- Subjects previously treated with any systemic therapy for multiple myeloma. Patients are allowed corticosteroids during screening not \>160 mg of dexamethasone (or equivalent). Patients with concurrent radiotherapy (localized) within the 14 days before initiating induction therapy are not eligible (If possible, in these cases, enrolment should be deferred).
- Subject with ongoing Grade ≥ 3 peripheral sensory or motor neuropathy.
- Subject with history of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
- Subject with a current diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or solitary plasmacytoma.
- Subject has a diagnosis of Waldenström's macroglobulinemia, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
- The subject has had plasmapheresis within 14 days of initiating induction therapy.
- Subject with clinical signs of meningeal involvement of multiple myeloma.
- The subject has plasma cell leukemia (by WHO criterion: ≥5% of plasma cells in the peripheral blood) or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
- Subject has any concurrent medical or psychiatric condition or disease (e.g., active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary 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:
- Subject has had myocardial infarction within 1 year before initiating induction therapy, or currently has an unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association \[NYHA\] class III IV).
- Subject has uncontrolled cardiac arrhythmia (common terminology criteria for adverse events \[CTCAE\] version 4 grade ≥2) or clinically significant electrocardiography (ECG) abnormalities.
- Subject with a baseline QT interval as corrected by Fridericia's formula (QTcF) \>470 msec (12-lead ECG).
- Subjects taking systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort (millepertuis) within the 14 days before initiating induction therapy.
- Known intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study intervention that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents.
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Intergroupe Francophone du Myelomelead
- Pfizercollaborator
Study Sites (64)
CHU Amiens
Amiens, France
CHU Angers
Angers, France
Ch Annecy Genevois
Annecy, France
Centre Hospitalier d'Argenteuil Victor Dupouy
Argenteuil, France
Centre Hospitalier H. Duffaut
Avignon, France
Centre hospitalier de la Côte Basque
Bayonne, France
CHU Besançon
Besançon, France
Centre Hospitalier Simone Veil
Blois, France
Hôpital Avicenne
Bobigny, France
CHU Bordeaux - Hopital Haut Lévêque - Centre F. Magendi
Bordeaux, France
CH Fleyriat
Bourg-en-Bresse, France
CHRU Brest - Hôpital A. Morvan
Brest, France
CHU Caen - Côte de Nacre
Caen, France
Centre Hospitalier William Morey
Chalon-sur-Saône, France
CHMS Centre Hospitalier Métropole Savoie
Chambéry, France
Hopital Louis Pasteur
Chartres, France
Hôpital d'Instruction des Armées Percy
Clamart, France
Chu Estaing
Clermont-Ferrand, France
Centre Hospitalier Sud Francilien
Corbeil-Essonnes, France
CHU Henri Mondor
Créteil, France
CHU Dijon
Dijon, France
Institut de cancérologie de Bourgogne
Dijon, France
Centre Hospitalier de Dunkerque
Dunkirk, France
CHU de Grenoble
Grenoble, France
CHU de la Réunion Site SUD (Terre Sainte)
La Réunion, France
CHD Vendée
La Roche-sur-Yon, France
Hopital Monod
Le Havre, France
CH Le mans
Le Mans, France
CHRU Hôpital Claude Huriez
Lille, France
Centre Hospitalier Universitaire (CHU) de Limoges
Limoges, France
Centre Hospitalier Lyon Sud
Lyon, France
Grand Hopital Est Francilien (GHEF) Site de Meaux
Meaux, France
Hôpital de Mercy (CHR Metz-Thionville)
Metz, France
Centre de Recherche Clinique / GHT des Landes
Mont-de-Marsan, France
Hopital Saint Eloi - CHU Montpellier
Montpellier, France
Hôpital E. Muller
Mulhouse, France
CHRU Hôpitaux de Brabois
Nancy, France
CHRU Hôtel Dieu
Nantes, France
Hôpital Archet 1
Nice, France
CHU Carémeau, Institut de Cancérologie du Guard
Nîmes, France
CHR Orléans
Orléans, France
CHU Hôpital Saint Antoine
Paris, France
Hôpital Cochin
Paris, France
Hôpital Necker
Paris, France
Hôpital Saint Louis
Paris, France
La Pitié Salpêtrière
Paris, France
CH Saint Jean
Perpignan, France
Centre Hospitalier de Perigueux
Périgueux, France
CHU Poitiers - Pôle régional de Cancérologie
Poitiers, France
Centre hospitalier René Dubost
Pontoise, France
Centre Hospitalier de Quimper Cornouaille
Quimper, France
Hôpital Robert Debré
Reims, France
CHRU Hôpital de Pontchaillou
Rennes, France
Centre Henri Becquerel
Rouen, France
Centre Hospitalier Saint Brieuc
Saint-Brieuc, France
Institut de Cancérologie Lucien Neuwirth
Saint-Priest, France
Centre Hospitalier de Saint-Quentin
Saint-Quentin, France
CHU Strasbourg
Strasbourg, France
Centre hospitalier
Tarbes, France
Pôle IUCT Oncopole CHU
Toulouse, France
CHRU Hôpital Bretonneau - Centre Henry Kaplan
Tours, France
CH Bretagne Atlantique Vannes et Auray - P. Chubert
Vannes, France
CHV André Mignot - Université de Versailles
Versailles, France
Gustave Roussy
Villejuif, France
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Chanaz LOUNI
The Institute for Functional Medicine
- PRINCIPAL INVESTIGATOR
Aurore PERROT, Prof
IUCT Toulouse France
- PRINCIPAL INVESTIGATOR
Cyrille TOUZEAU, Prof
CHU Nantes France
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 10, 2024
First Posted
April 9, 2025
Study Start
July 9, 2025
Primary Completion (Estimated)
May 1, 2036
Study Completion (Estimated)
May 1, 2036
Last Updated
April 2, 2026
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will not share