IFM 2017-03
- Conditions
- A Phase III Study Comparing Lenalidomide and Daratumumab (R-Dara) vs Lenalidomide and Dexamethasone (Rd) in Frail Subjects with Previously Untreated Multiple Myeloma who are Ineligible for High Dose Therapy.MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003535-30-FR
- Lead Sponsor
- CHRU de Lille
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 294
1.Subject must be at least 65 years of age.
2.Subject must have documented multiple myeloma satisfying the CRAB criteria and measurable disease defined as:
•Monoclonal plasma cells in the bone marrow =10% or presence of a biopsy proven plasmacytoma
•Measurable disease as defined by any of the following:
-IgG myeloma: Serum monoclonal paraprotein (M-protein) level =1.0 g/dL or urine M-protein level =200 mg/24 hours; or
-IgA, IgM, IgD, or IgE multiple myeloma: serum M-protein level =0.5 g/dL or urine M-protein level =200 mg/24 hours; 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).
3.Newly diagnosed and not considered candidate for high-dose chemotherapy with SCT.
4.Subject must have a Frailty Score = 2
5.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);
6. Measurable ISS with ß2-microglobulin and albumin values for randomization
7.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 lenalidomide, and for 4 months after the last dose of daratumumab. Women participating in this study must be postmenopausal.
8.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.
9. Subjects affiliated with an appropriate social security system.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age
1.Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma.
2.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.
3.Subject has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment.
4.Subject has a history of malignancy (other than multiple myeloma) 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).
5.Subject has had radiation therapy within 14 days of randomization.
6.Subject has had plasmapheresis within 28 days of randomization.
7.Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma.
8.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.
9.Subject is known to be seropositive for history of human immunodeficiency virus (HIV) or known to have HBV infection (HBsAG positive at screening) or active hepatitis C
10.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.
11.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
12.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).
13.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).
14.Subject is known or suspected of not being able to comply with the study protocol (eg, because of alcoholism,
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method