Authorised Therapeutic confirmatory (Phase III) Multiple Myeloma

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)

EU CTIS ID: 2024-516418-39-00

What this study is testing

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

Therapeutic confirmatory (Phase III)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1. Male or female subjects, aged ≥18 but < 70 years old.
2. Patients have provided voluntary written informed consent before performing any study-related procedure.
3. Patients with newly diagnosed multiple myeloma (NDMM) eligible for high-dose chemotherapy (melphalan) and autologous stem cell transplantation (ASCT).
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. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2.
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).

You likely can't join if

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).
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. 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. 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. Known allergies to any of the study medications, their analogues, or excipients in the various formulations
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.

See the full eligibility criteria

Who can join

1. Male or female subjects, aged ≥18 but < 70 years old.
2. Patients have provided voluntary written informed consent before performing any study-related procedure.
3. Patients with newly diagnosed multiple myeloma (NDMM) eligible for high-dose chemotherapy (melphalan) and autologous stem cell transplantation (ASCT).
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. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2.
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. 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.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.

What rules you out

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).
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. 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. 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. Known allergies to any of the study medications, their analogues, or excipients in the various formulations
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. 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. Pregnant or breast-feeding women.
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. 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. 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.
2. Subject with ongoing Grade ≥ 3 peripheral sensory or motor neuropathy.
20. Patient with an active systemic infection or severe infections requiring parenteral administration of antibiotics
21. Patients with a gastrointestinal disease/disorder that may significantly impact the absorption of oral treatments.
22. Patients unable or unwilling to undergo antithrombic prophylaxis.
23. A person under guardianship, trusteeship, or deprived of freedom by a judicial or administrative decision.
3. Subject with history of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
4. Subject with a current diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or solitary plasmacytoma.
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. The subject has had plasmapheresis within 14 days of initiating induction therapy.
7. Subject with clinical signs of meningeal involvement of multiple myeloma.
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. 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.

The study team makes the final eligibility decision.

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.