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 (ElLen; IFM 2025-01)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Intergroupe Francophone Du Myelome

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Jul 2025 → ongoing

Decision date (initial)

2025-05-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Pfizer INC.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Safety, Efficacy

Dual primary objectives :
- To assess whether consolidation therapy with elranatamab and lenalidomide is superior to standard of care, in terms of MRD negativity rate
- To assess whether maintenance therapy with elranatamab is superior to standard of care, in terms of PFS

Secondary objectives 6

1. To assess whether consolidation therapy with elranatamab and lenalidomide is superior in terms of PFS
2. To assess whether consolidation therapy with elranatamab and lenalidomide is superior to standard of care, in terms of OS
3. To assess the efficacy of consolidation therapy with elranatamab and lenalidomide compared to standard of care.
4. To assess the efficacy of maintenance therapy with elranatamab
5. To assess safety during induction, and during consolidation and maintenance therapy.
6. To evaluate the impact of treatment on health-related QoL.

Conditions and MedDRA coding

Multiple Myeloma

Study design 1 period

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003083-PIP01-21

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Male or female subjects, aged ≥18 but < 70 years old.
2. 2. Patients have provided voluntary written informed consent before performing any study-related procedure.
3. 3. Patients with newly diagnosed multiple myeloma (NDMM) eligible for high-dose chemotherapy (melphalan) and autologous stem cell transplantation (ASCT).
4. 4. 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.
5. 5. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2.
6. 6. Patients must have clinical laboratory values (within 15 days of initiating induction therapy) as follows: • Hemoglobin ≥7.5 g/dL (≥5 mmol/L). Prior red blood cell (RBC) transfusion or the use of recombinant human erythropoietin is permitted. • Absolute neutrophil count (ANC) ≥1.0 G/L (granulocyte colony stimulating factor [G-CSF] use is permitted). • Aspartate aminotransferase (AST) ≤3 x ULN. • Alanine aminotransferase (ALT) ≤ 3 x ULN. • Total bilirubin ≤3 x ULN (except in subjects with congenital bilirubinemia, such as Gilbert syndrome, that require a direct bilirubin ≤3 x ULN). • Calculated creatinine clearance ≥40 mL/min/1.73 m² using CKD-EPI.• Albumin corrected serum calcium ≤14 mg/dL (<3.5 mmol/L); or free-ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L). • Platelet count ≥50 Giga/L for subjects who have <50% of bone marrow nucleated cells as plasma cells. If not, platelet count >30 G/L (platelets transfusions done during the 15 days before initiating induction therapy are not permitted).
7. 7. Women of childbearing potential must have a negative serum or urine pregnancy test during the screening period before randomization AND within 3 days before initiating induction therapy.
8. 8.Patients must be willing and able to comply with scheduled appointments, treatment plan, laboratory tests, and other study procedures (such as blood transfusion if required, ASCT, IVIG prophylaxis, etc.

Exclusion criteria 23

1. 1. Subjects previously treated with any systemic therapy for multiple myeloma. Patients are allowed corticosteroids before or during screening , as far as the total dose received is not >160 mg of dexamethasone (or equivalent) within 14 days before initiating induction therapy. Patients with concurrent radiotherapy within the 14 days before initiating induction therapy are not eligible (If possible, in these cases, enrolment should be deferred).
2. 2. Subject with ongoing Grade ≥ 3 peripheral sensory or motor neuropathy.
3. 3. Subject with history of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
4. 4. Subject with a current diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or solitary plasmacytoma.
5. 5. 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.
6. 6. The subject has had plasmapheresis within 14 days of initiating induction therapy.
7. 7. Subject with clinical signs of meningeal involvement of multiple myeloma.
8. 8. 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).
9. 9. 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.
10. 10. Subject has clinically significant cardiac disease, including: a. 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). b. Subject has uncontrolled cardiac arrhythmia (common terminology criteria for adverse events [CTCAE] version 4 grade ≥2) or clinically significant electrocardiography (ECG) abnormalities. c. Subject with a baseline QT interval as corrected by Fridericia’s formula (QTcF) >470 msec (12-lead ECG).
11. 11. 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.
12. 12. 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.
13. 13. Known allergies to any of the study medications, their analogues, or excipients in the various formulations
14. 14. Subjects who have had major surgery within 2 weeks before study inclusion (signing of the informed consent) OR will not have fully recovered from surgery before initiating induction therapy OR have surgery planned during their study participation. Kyphoplasty and vertebroplasty are not considered as major surgery.
15. 15. Subjects with any prior or concurrent malignancy (other than multiple myeloma) within 5 years of study inclusion study, except for adequately treated basal cell or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, or localized prostate adenocarcinoma diagnosed ≥3 years ago and without evidence of biological failure, or other cancers for which the subject has undergone potentially curative therapy and has shown no evidence of relapse/recurrence for ≥5 years.
16. 16. Pregnant or breast-feeding women.
17. 17. Women that refuse to abstain from heterosexual intercourse or refuse to use adequate contraceptives during heterosexual intercourse starting at least 4 weeks before initiating induction therapy and continually until at least 4 weeks after discontinuing lenalidomide, 90 days after discontinuing daratumumab and 6 months after discontinuing elranatamab.
18. 18. Men with partners of childbearing potential, even men with a successful vasectomy, that refuse to use a condom during intercourse, from initiating induction therapy to ≥ 4 weeks after discontinuing lenalidomide. Furthermore, men must agree to not donate sperm during this period.
19. 19. Known positive for HIV or active hepatitis A, B or C: Uncontrolled or active HBV infection: Patients with positive HBsAg and/or HBV DNA Of note: Patients can be eligible if anti-HBc IgG positive (with or without positive anti-HBs) but HBsAg and HBV DNA are negative. a. If anti-HBV therapy in relation to prior infection was started before initiation of IMP, the anti-HBV therapy and monitoring should continue throughout the study treatment period. Patients with negative HBsAg and positive HBV DNA observed during screening period will be evaluated by a specialist for start of anti-viral treatment: study treatment could be proposed if HBV DNA becomes negative, and all the other study criteria are still met. Active HCV infection: positive HCV RNA and negative anti-HCV. Of note: Patients with antiviral therapy (Direct-acting antivirals (DAAs)) for HCV started before initiation of IMP and positive HCV antibodies are eligible. The antiviral therapy for HCV should continue throughout the treatment period until seroconversion. Patients with positive anti-HCV and undetectable HCV RNA without antiviral therapy for HCV are eligible. HIV infection: Of note: In equivocal cases, participants whose viral load is negative may be eligible. HIV seropositive participants who are otherwise healthy and at low risk for AIDS related outcomes could be considered eligible. Potential eligibility for a specific HIV positive protocol candidate should be evaluated and discussed with the sponsor prior to screening, considering current and past CD4+ and T-cell counts, history (if any) of AIDS defining conditions (eg, opportunistic infections), status of HIV treatment and the potential for drug-drug interactions.
20. 20. Patient with an active systemic infection or severe infections requiring parenteral administration of antibiotics
21. 21. Patients with a gastrointestinal disease/disorder that may significantly impact the absorption of oral treatments.
22. 22. Patients unable or unwilling to undergo antithrombic prophylaxis.
23. 23. A person under guardianship, trusteeship, or deprived of freedom by a judicial or administrative decision.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. MRD negativity rate as determined by NGS with a sensitivity of at least 10-5 measured at end of consolidation
2. PFS R2 defined as the time interval from the date of second randomization to the date of confirmed PD (IMWG criteria) or death from any cause, whichever occurs first.

Secondary endpoints 6

1. PFS R1 defined as the time interval from the date of first randomization to the date of confirmed PD (IMWG criteria) or death from any cause, whichever occurs first.
2. OS R1 defined as the time interval from the date of first randomization to the date of death from any cause
3. - Overall response rate (ORR) - Very good partial response (VGPR) rate - Complete response (CR) rate - Sustained MRD negativity rate at 24 months defined as the proportion of participants with CR per IMWG criteria and MRD negativity at 12 months after R1 which is sustained at 24 months after R1
4. - Overall response rate (ORR) in maintenance - Very good partial response (VGPR) rate in maintenance - Complete response (CR) rate in maintenance - PFS of subsequent/next treatment line (PFS2 from R2) - Overall survival from second randomization (OS R2)
5. Incidence and severity of AEs
6. QoL will be assessed using the following instruments: • EORTC QLQ-C30, • EUROQOL (EQ-5D-5L) • Return to work questionnaires

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 5

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Intergroupe Francophone Du Myelome

Sponsor organisation

Intergroupe Francophone Du Myelome

Address

75 Avenue Parmentier

City

Paris Cedex 11

Postcode

75544

Country

France

Scientific contact point

Organisation

Intergroupe Francophone Du Myelome

Contact name

Pr Cyrille TOUZEAU and Pr Aurore PERROT

Public contact point

Organisation

Intergroupe Francophone Du Myelome

Contact name

Léa TABONE

Third parties 6

Locations

1 EU/EEA country · 65 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications