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A Phase 3 Study Comparing Lenalidomide and Daratumumab Subcutaneous Injection (R-Dara SC) vs Lenalidomide and Dexamethasone (Rd) in Frail Subjects with Previously Untreated Multiple Myeloma who are Ineligible for High Dose Therapy.
EU CTIS ID: 2024-514088-25-00
What this study is testing
The primary objective is to compare the efficacy of daratumumab SC injection when combined with lenalidomide (R-Dara SC) to that of lenalidomide and dexamethasone (Rd), in terms of PFS in frail subjects with newly diagnosed myeloma who are not candidates for high dose chemotherapy and autologous stem cell transplant.
- 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
- Subject must be at least 65 years of age
- Subject must have documented multiple myeloma satisfying the CRAB riteria and measurable disease defined as: 1-Monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy proven plasmacytoma 2-Measurable disease as defined by any of the following: - IgG myeloma: Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL; or - IgA, IgM, IgD, or IgE multiple myeloma: serum M-protein level ≥0.5 g/dL ; or - Light chain multiple myeloma: Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio (only measurable with freelite® by Binding site); or - Urine M-protein level ≥200 mg/24 hours
- Newly diagnosed and not considered candidate for high-dose chemotherapy with SCT
- Subject must have a Frailty Score ≥ 2
- Subject must have within 5 days prior to first drug intake (C1D1) pretreatment clinical laboratory values meeting the following criteria during the Screening Phase: a) hemoglobin ≥7.5 g/dL (≥4.65 mmol/L; prior red blood cell [RBC] transfusion or recombinant human erythropoietin use is permitted); b) absolute neutrophil count ≥1.0 x 109/L (granulocyte colony stimulating factor [GCSF] use is permitted); c) platelet count ≥70 x 109/L for subjects in whom <50% of bone marrow nucleated cells are plasma cells; otherwise platelet count >50 × 109/L (transfusions are not permitted to achieve this minimum platelet count). d) aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN); e) alanine aminotransferase (ALT) ≤2.5 x ULN; f) total bilirubin ≤2.0 x ULN, except in subjects with congenital bilirubinemia, such as Gilbert syndrome (direct bilirubin ≤2.0 x ULN); g) creatinine clearance≥30mL/min(for lenalidomide dose adjustment for subjects with creatinine clearance 30-60 mL/min). Creatinine clearance may be calculated using the Cockcroft-Gault formula h) corrected serum calcium ≤14 mg/dL (≤3.5 mmol/L)
- Measurable ISS with β2-microglobulin and albumin values for randomization
You likely can't join if
- Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma.
- Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
- (Known to be) seropositive for hepatitis C.
- Subject has any concurrent medical or psychiatric condition or disease (eg, 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: myocardial infarction within 1 year before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV uncontrolled cardiac arrhythmia (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 4 Grade ≥ 2) or clinically significant ECG abnormalities screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec
- Subject has known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or Investigator's Brochure).
See the full eligibility criteria
Who can join
- Subject must be at least 65 years of age
- Subject must have documented multiple myeloma satisfying the CRAB riteria and measurable disease defined as: 1-Monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy proven plasmacytoma 2-Measurable disease as defined by any of the following: - IgG myeloma: Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL; or - IgA, IgM, IgD, or IgE multiple myeloma: serum M-protein level ≥0.5 g/dL ; or - Light chain multiple myeloma: Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio (only measurable with freelite® by Binding site); or - Urine M-protein level ≥200 mg/24 hours
- Newly diagnosed and not considered candidate for high-dose chemotherapy with SCT
- Subject must have a Frailty Score ≥ 2
- Subject must have within 5 days prior to first drug intake (C1D1) pretreatment clinical laboratory values meeting the following criteria during the Screening Phase: a) hemoglobin ≥7.5 g/dL (≥4.65 mmol/L; prior red blood cell [RBC] transfusion or recombinant human erythropoietin use is permitted); b) absolute neutrophil count ≥1.0 x 109/L (granulocyte colony stimulating factor [GCSF] use is permitted); c) platelet count ≥70 x 109/L for subjects in whom <50% of bone marrow nucleated cells are plasma cells; otherwise platelet count >50 × 109/L (transfusions are not permitted to achieve this minimum platelet count). d) aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN); e) alanine aminotransferase (ALT) ≤2.5 x ULN; f) total bilirubin ≤2.0 x ULN, except in subjects with congenital bilirubinemia, such as Gilbert syndrome (direct bilirubin ≤2.0 x ULN); g) creatinine clearance≥30mL/min(for lenalidomide dose adjustment for subjects with creatinine clearance 30-60 mL/min). Creatinine clearance may be calculated using the Cockcroft-Gault formula h) corrected serum calcium ≤14 mg/dL (≤3.5 mmol/L)
- Measurable ISS with β2-microglobulin and albumin values for randomization
- A man who is sexually active with a woman of childbearing potential must agree to use a latex or synthetic condom, even if they had a successful vasectomy. All men must also not donate sperm during the study, for 4 weeks after the last dose of lenalidomid, and for 4 months after the last dose of daratumumab. Women participating in this study must be postmenopausal
- Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol, as referenced in the ICF
- Subjects affiliated with an appropriate social security system
What rules you out
- Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma.
- Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR.
- (Known to be) seropositive for hepatitis C.
- Subject has any concurrent medical or psychiatric condition or disease (eg, 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: myocardial infarction within 1 year before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV uncontrolled cardiac arrhythmia (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 4 Grade ≥ 2) or clinically significant ECG abnormalities screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec
- Subject has known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or Investigator's Brochure).
- Subject has plasma cell leukemia (according to World Health Organization [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).
- Subject is known or suspected of not being able to comply with the study protocol (eg, because of alcoholism, drug dependency, or psychological disorder). Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. Subject is taking any prohibited medications as per Section 8.3.
- Subject has had major surgery within 2 weeks before randomization or has not fully recovered from surgery.
- Subject has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before randomization or is currently enrolled in an interventional investigational study.
- Refusal to consent or protected by legal regime ( guardianship, trusteeship)
- Subject has a diagnosis of Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
- Subject has contraindications to required prophylaxis for deep vein thrombosis and pulmonary embolism
- Incidence of gastrointestinal disease that may significantly alter the absorption of oral drugs.
- Subject has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course of corticosteroids before treatment.
- Subject has a history of malignancy within 5 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 5 years).
- Subject has had radiation therapy within 14 days of randomization.
- Subject has had plasmapheresis within 28 days of randomization.
- Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma.
- Subject has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume [FEV] in 1 second <60% of predicted normal), persistent asthma, or a history of asthma within the last 2 years (intermittent asthma is allowed). Subjects with known or suspected COPD or asthma must have a FEV1 test during screening.
- Subject is known to be seropositive for history of human immunodeficiency virus (HIV)
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. The study team makes the final eligibility decision.
Explore other conditions
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.