Phase 2 Randomized Study of Elranatamab and Lenalidomide Versus Daratumumab and Lenalidomide for Post-Transplant Maintenance in Newly Diagnosed Multiple Myeloma
- Trial ID
- 2024-517325-43-00
- Protocol
- RC23_0603
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the **efficacy** of elranatamab plus lenalidomide versus daratumumab plus lenalidomide as post-transplant maintenance therapy in patients with newly-diagnosed **multiple myeloma**. This comparison is clinically relevant as it aims to identify the most effective maintenance therapy to improve patient outcomes following autologous stem cell transplantation.
Secondary objectives include:
- Determining the effect of elranatamab plus lenalidomide on minimal residual disease (MRD) negativity at one and two years post-randomization, with specific thresholds (NGS, 10-5 and 10-6).
- Evaluating the safety and tolerability of both maintenance therapies.
- Assessing sustained MRD negativity and the rate of complete response (CR) or better.
- Comparing overall survival (OS) and progression-free survival (PFS) between the two treatment arms.
- Investigating progression-free survival 2 (PFS2) and the ability of patients to return to work.
- Identifying biological prognostic factors influencing treatment outcomes and response.
- Assessing quality of life (QoL) in patients undergoing these maintenance therapies.
Participants
The clinical trial involves participants diagnosed with **multiple myeloma**. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a documented diagnosis of multiple myeloma according to the International Myeloma Working Group criteria and must have undergone specific prior treatments, including high-dose melphalan and autologous stem cell transplant (ASCT). The trial does not include a vulnerable population. Participants must have a Karnofsky performance status score of at least 50% and meet specific clinical laboratory criteria. Lifestyle considerations such as diet and physical activity are not specified. The sponsor has not provided information regarding the total number of participants in the trial.
Plans and Procedures
The clinical trial is a **randomized**, open-label, phase 2 study designed to evaluate the efficacy of **elranatamab** plus **lenalidomide** compared to **daratumumab** plus lenalidomide as post-transplantation maintenance therapy in patients with newly diagnosed **multiple myeloma**. The trial will involve a series of study visits over an estimated duration of 24 months, with participant involvement expected to last until the end of the study or until early termination criteria are met. The trial is set to commence recruitment in March 2025 and is anticipated to conclude by September 2031.
Participants will undergo an initial screening visit to confirm eligibility based on inclusion criteria such as age, documented diagnosis of multiple myeloma, and previous treatment history. Following successful screening, participants will be randomized to receive either the elranatamab plus lenalidomide regimen or the daratumumab plus lenalidomide regimen. The primary endpoint is the rate of minimal residual disease (MRD) negativity after 12 cycles of maintenance therapy, assessed on Cycle 13 Day 1. Secondary endpoints include MRD status at one and two years post-randomization, progression-free survival, and overall survival.
Study visits will be scheduled regularly to monitor treatment efficacy and safety, with assessments including laboratory tests, imaging, and clinical evaluations. Participants will be required to attend follow-up visits every three cycles, with additional visits as needed for safety monitoring. The end-of-study visit will occur after the completion of 24 cycles or upon early termination. Conditions for early termination include disease progression, unacceptable toxicity, or withdrawal of consent. Participants are expected to adhere to the study protocol, including the use of effective contraception for those of childbearing potential, to ensure the integrity of the trial data.
Treatment
The clinical trial involves the administration of **LENALIDOMIDE**, an experimental medication, in the form of hard capsules. The active substance, lenalidomide, is of chemical origin. The medication is administered orally with a maximum daily dose of 10 mg and a total maximum dose of 5040 mg over a treatment period of 24 months. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen.
**ELRANATAMAB** is another experimental medication used in this trial, provided as a solution for injection. The active substance, elranatamab, is a protein of other origin. The medication is administered subcutaneously with a maximum daily dose of 76 mg and a total maximum dose of 2096 mg over a 24-month treatment period. The administration schedule and participant compliance will be closely monitored to maintain the integrity of the study.
**DARATUMUMAB** is used as a comparator treatment in this study, also provided as a solution for injection. The active substance, daratumumab, is a protein of other origin. It is administered subcutaneously with a maximum daily dose of 1800 mg and a total maximum dose of 43.2 g over a 24-month treatment period. The dosing schedule and participant adherence will be systematically monitored to ensure accurate data collection and analysis.
Efficacy
The efficacy of the clinical trial will be assessed primarily through the **Minimal Residual Disease (MRD)** negativity rate, evaluated at a sensitivity level of 10-6 using Next-Generation Sequencing (NGS). This primary endpoint will be measured after 12 cycles of maintenance therapy, specifically on Cycle 13, Day 1. Secondary endpoints include the rate of MRD negativity at one year and two years post-randomization, with assessments scheduled on Cycle 13, Day 1, and Cycle 25, Day 1, respectively. Additional secondary endpoints encompass the rate of patients achieving MRD negativity for at least 12 months, the rate of complete response or better as defined by the International Myeloma Working Group (IMWG) 2016 criteria, overall survival (OS), progression-free survival (PFS), and PFS2. The presence and severity of treatment-emergent adverse events (TEAEs) will be evaluated using the NCI CTCAE Version 5.0, except for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which will be assessed based on ASTCT guidelines. Patient-reported outcomes will be measured using the EQ-5D-5L and EORTC QLQ-C30 scores at various timepoints, including screening, the start of maintenance, every third cycle, end of treatment, and follow-up before disease progression.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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 ≤2×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 Lenalidomideor 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
Exclusion Criteria
- Subjects have received any prior anti BCMA therapy
- Subject have received post transplantation maintenance therapy
- Subject intolerant to lenalidomide or having 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.
- Female subject who is pregnant or breast-feeding.
- Serious medical or psychiatric illness likely to interfere with participation in study.
- Uncontrolled diabetes mellitus.
- Active HBV, HCV, SARS-CoV-2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection. Active infections must be resolved at least 21 days prior to enrollment. Treatment with systemic anti-infective agents must have completed at least 28 days prior to enrollment. Prophylactic use of systemic agents is permitted. • COVID-19/SARS-CoV-2: SARS-CoV-2 PCR testing is mandated within 5 days prior to enrollment. Participants with positive PCR test result for SARS-CoV-2 within 5 days prior to enrollment, or suspected of having SARS-CoV-2, are excluded. • HIV: 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. • HBV: - Participants with a positive HBsAg test (ie, either acute or chronic active hepatitis) are excluded. - Participants with HBV antibody positivity indicating immunity, either due to vaccination or prior natural infection, are eligible. - Participants with positive anti-HBcAb but negative HBsAg and negative anti-HBsAb profile are eligible if HBV DNA is not detected. • HCV: Positive HCV antibody is indicative of infection but may not necessarily render a potential candidate ineligible, depending on clinical circumstances. If exposure to HCV is recent, HCV antibody may not have yet turned positive. In these circumstances it is recommended to test for HCV RNA. If HCV RNA is detected, the patient is not eligible.
- Subjects unable or unwilling to undergo antithrombotic prophylactic treatment.
- Incidence of gastrointestinal disease that may significantly alter the absorption of oral drugs.
- Person under guardianship, trusteeship or deprived of freedom by a judicial or administrative decision.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 01 Mar 2025 | 176 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
LENALIDOMIDE | Other | — | ORAL USE | 10 | 24 | SUB25389 |
DARATUMUMAB | Comparator | — | SUBCUTANEOUS USE | 1800 | 24 | SUB175772 |
LENALIDOMIDE | Other | — | ORAL USE | 10 | 24 | SUB25389 |
ELRANATAMAB | Test | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 76 | 24 | PRD10297333 |