Comparison of Elranatamab and Lenalidomide Versus Daratumumab and Lenalidomide as Post-transplant Maintenance Therapy in Patients With Newly Diagnosed Myeloma (ElMMA)

NCT06931704 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: RC23_0603
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 36

Brief Summary

Lenalidomide is a standard of care for maintenance therapy after autologous stem cell transplantation in newly diagnosed myeloma patients. Recently, two large phase 3 randomized trials demonstrated a progression free survival benefit with daratumumab maintenance post autologous stem cell transplantation. Bispecific antibodies targeting B-Cell Maturation Antigen are approved for the treatment of relapsed refractory myeloma patients after 3 prior lines of therapy including proteasome inhibitor, immunomodulator IMiD and anti CD38 monoclonal antibody. In the cohort A of the MAGNETISMM-3 phase 2 study (n=123), elranatamab single-agent demonstrated strong efficacy with favorable safety profile in patients with advanced multiple myeloma (median of 5 prior lines, 96% of patients with triple class refractory disease). Lenalidomide has been shown to promote cytotoxic activity of CD3 bispecific antibodies. 7We propose a phase 2 randomized study comparing elranatamab plus lenalidomide versus daratumumab plus lenalidomide for 2 years as post-transplant maintenance in patients with newly diagnosed multiple myeloma. The primary objective is minimal residual disease rate after one year of maintenance. Secondary objectives include Progression-Free Survival, safety, quality of life, return to work and overall survival.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; maintenance; elranatamab; lenalidomide; daratumumab

Outcome Measures

Primary Outcomes (1)

• Minimal Residual Disease negativity rate

  Minimal Residual Disease negativity rate (10-6, NGS) status after 12 cycles of maintenance

  At the beginning of cycle 13 (each cycle is 28 days)

Secondary Outcomes (9)

• Safety and tolerability of Dara-Len and Elra-Len

  4 years

• Progression-free survival

  4 years

• Minimal Residual Disease negativity with the threshold evaluated at one year after randomisation

  At the beginning of cycle 13 (each cycle is 28 days)

• Minimal Residual Disease negativity with the threshold evaluated at one two years

  At the beginning of cycle 25 (each cycle is 28 days)

• Sustained Minimal Residual Disease negativity

  At the beginning of cycle 13 and 25 (each cycle is 28 days)

Other Outcomes (3)

• Determine biological prognostic factors influencing Minimal Residual Disease

  At screnning (Baseline)

• Determine biological prognostic factors influencing complete response.

  At screnning (Baseline)

• Descriptive quality of life

  At Screening, At the beginning of every 3 cycles (each cycle is 28 days), at the beginning of cycle 24, and during the Follow-Up before Progressive Disease

Study Arms (2)

Usual care : Daratumumab + Lenalidomide

ACTIVE COMPARATOR

Drug: Daratumumab; Drug: Lenalidomide

Comparative treatment : Elranatamab + Lenalidomide

EXPERIMENTAL

Drug: Elranatamab; Drug: Lenalidomide

Interventions

Elranatamab DRUG

Each injection may be up to 2 mL in volume; however, if the maximum volume allowed per institution's policy is lower than 2 mL, the number of injections may be increased to accommodate this difference in volume and ensure the correct dose is delivered. Elranatamab should be administered to the abdomen, with preference given to the lower quadrants when possible. Each participant may receive study intervention for a maximum of 24 cycles.

Comparative treatment : Elranatamab + Lenalidomide

Daratumumab DRUG

1800 mg will be administrated every cycles

Usual care : Daratumumab + Lenalidomide

Lenalidomide DRUG

Daily administarted during 21 days, at each cycle

Comparative treatment : Elranatamab + Lenalidomide; Usual care : Daratumumab + Lenalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Male or female subjects, 18 years of age or older
• \- Voluntary written informed consent must be given before performance of any study-related procedure not part of normal medical care, with the understanding that the subject may withdraw consent at any time without prejudice to future medical care.
• \- Subject must have documented multiple myeloma according to International Myeloma Working Group (IMWG) criteria and have received 4 to 6 cycles of quadruplet-based therapy including proteasome inhibitor, IMID and anti CD38 monoclonal antibody.
• \- Subject must have received only one line of therapy and achieved at least a partial response as per IMWG 2016 criteria.
• \- Subject must have received high-dose melphalan and ASCT within 12 months of the start of induction therapy and be within 6 months of the last ASCT at the time of first treatment dose.
• \- Subject must have NGS analysis performed at time of MM diagnosis and/or adequate stored bone marrow material allowing NGS analysis (IUCT-Oncopole, Toulouse, France) in order to calibrate MRD analysis.
• \- Karnofsky performance status score ≥ 50% (eastern cooperative oncology group performance status ECOG score ≤ 2).
• \- Subject must have clinical laboratory values meeting the following criteria during the Screening Phase:
• Hematology : Hemoglobin \>8.0 g/dL without prior RBC transfusion within 7 days before the laboratory test; recombinant human erythropoietin use is permitted) + Platelets ≥75×109/L (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test) + Absolute neutrophil count ≥1.0×109/L (prior growth factor support is permitted but must be without support for 7 days for G-CSF or 14 days for pegylated-G-CSF)
• Chemistry : AST and ALT ≤2.5× upper limit of normal (ULN) + CrCl ≥30 mL/min based on Cockroft-Gault formula calculation or a 24-hour urine collection + Total bilirubin ≤1.5×ULN; except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5×ULN is required) + Serum calcium corrected for albumin ≤14 mg/dL (≤3.5 mmol/L)
• \- Women of childbearing potential must have a negative serum or urine pregnancy test within 10 to 14 days prior to therapy and repeated within 24 hours before starting study drug. They must commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control (One highly effective method and one additional effective method) used at the same time, beginning at least 4 weeks before initiation of lenalidomide treatment and continuing for at least 6 months after the last dose of Lenalidomide or Elranatamab depending on the last treatment taken. Highly effective contraceptive methods are defined as any of the following methods: combined hormonal contraception (containing estrogen and progestin) combined with ovulation inhibition (oral, intravaginal, transdermal), progestin-only hormonal contraception combined with ovulation inhibition (oral, injectable, implantable), intrauterine device (IUD), hormone-releasing intrauterine system (IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence.Women must also agree to notify pregnancy during the study.
• \- Men must agree to not father a child and agree to use a latex condom during therapy and for 6 months after the last dose of study drug, even if they have had a successful vasectomy, if their partner is of childbearing potential.

You may not qualify if:

• \- Subjects have received any prior anti BCMA therapy.
• \- Subject have received post transplantation maintenance therapy.
• \- Subject intolerant to lenalidomide or have discontinued treatment due to any AE related to lenalidomide.
• \- Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma.
• \- Myocardial infarction within 6 months prior to enrollment according to NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• \- Uncontrolled hypertension.
• \- Subjects with known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) \< 50% of predicted normal. Note that FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV1 \< 50% of predicted normal.
• \- Subjects with a history of moderate or severe persistent asthma within the past 2 years, or with uncontrolled asthma of any classification at the time of screening (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).
• \- Subject has plasma cell leukemia (according to WHO criterion: ≥ 20% of cells in the peripheral blood with an absolute plasma cell count of more than 2 × 109/L) or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
• \- 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 within 14 days before the first dose of study treatment.
• \- Known intolerance to steroid therapy.
• \- History of allergy to any of the study medications, their analogues, or excipients in the various formulations.
• \- Subject has had major surgery within 2 weeks before randomization or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study. Kyphoplasty or Vertebroplasty are not considered major surgery.
• \- Clinically relevant active infection or serious co-morbid medical conditions.
• \- Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer free of disease since 5 years.

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (36)

CHU Angers

Angers, France

Location

CH Côte Basque

Bayonne, France

Location

CHU Besançon

Besançon, France

Location

CHU Caen

Caen, France

Location

Hôpital d'Instruction des Armées Percy

Clamart, France

Location

CHU Clermont- Ferrand - Hôpital ESTAING

Clermont-Ferrand, France

Location

Hôpital Henri Mondor

Créteil, France

Location

CHRU Dijon

Dijon, France

Location

Institut de cancérologie de Bourgogne

Dijon, France

Location

Hôpital Annecy Genevois

Épagny, France

Location

CHD Vendée

La Roche-sur-Yon, France

Location

CH Le Mans - Centre de cancérologie de la Sarthe

Le Mans, France

Location

CH de Libourne

Libourne, France

Location

CHU Limoges

Limoges, France

Location

Groupement Hospitalier Bretagne Sud

Lorient, France

Location

Centre Léon BERARD

Lyon, France

Location

IPC Marseille

Marseille, France

Location

CHRU Nancy

Nancy, France

Location

CHU Nantes

Nantes, France

Location

CHU de Nice - Hôpital l'Archet 1

Nice, France

Location

CHU de Nîmes - Institut de Cancérologie du Gard

Nîmes, France

Location

Hopital St Louis

Paris, France

Location

Hôpital Cochin

Paris, France

Location

Hôpital Necker

Paris, France

Location

Hôpital St Antoine

Paris, France

Location

CH Saint-Jean

Perpignan, France

Location

CHRU - Hôpital du Haut Lévêque

Pessac, France

Location

CH Périgueux

Périgueux, France

Location

CHU de Poitiers

Poitiers, France

Location

CH Cornouaille Quimper

Quimper, France

Location

CH de Saint Nazaire

Saint-Nazaire, France

Location

ICANS

Strasbourg, France

Location

CH Tarbes-Lourdes

Tarbes, France

Location

CHU Toulouse

Toulouse, France

Location

CHRU Bretonneau

Tours, France

Location

CH Bretagne Atlantique

Vannes, France

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; 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

Central Study Contacts

Cyrille TOUZEAU

CONTACT

02 40 08 32 71; cyrille.touzeau@chu-nantes.fr

Study Design

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

Study Record Dates

• First Submitted: April 1, 2025
• First Posted: April 17, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): November 30, 2030
• Study Completion (Estimated): November 30, 2031
• Last Updated: April 23, 2025

Record last verified: 2025-04

Locations

FR (36)