Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Participants With Previously Untreated Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Daratumumab IV; Lenalidomide; Dexamethasone; Daratumumab SC
Intervention description: Daratumumab will be administered at a dose of 16 milligram per kilogram (mg/kg) by intravenous (IV) infusion, once a week for 8 weeks, then once every other week for 16 weeks, thereafter once every 4 weeks until documented progression of disease, unacceptable toxicity, or end of study (maximum up to 7 years).; Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle.; Dexamethasone 40 mg orally or intravenously once in a week.; Daratumumab SC will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or study end. Following implementation of protocol amendment 8, participants still receiving treatment with daratumumab IV will have the option to switch to daratumumab SC on Day 1 of any cycle, at the discretion of the investigator.
Intervention MeSH terms: Dexamethasone; Lenalidomide; Daratumumab; Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 737.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Multiple Myeloma; Daratumumab; JNJ-54767414; Lenalidomide; Dexamethasone

Summary:

      The purpose of this study is to compare the efficacy of daratumumab in combination with
      lenalidomide and dexamethasone to that of lenalidomide and dexamethasone in terms of
      progression-free survival (PFS) in participants with newly diagnosed multiple myeloma (a
      blood cancer of plasma cells) who are not candidates for high dose chemotherapy (treatment of
      disease, usually cancer, by chemical agents) and autologous stem cell transplant (ASCT).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant must have documented multiple myeloma satisfying the CRAB (calcium
             elevation, renal insufficiency, anemia and bone abnormalities) criteria, monoclonal
             plasma cells in the bone marrow greater than or equal to (>=) 10 percent (%) or
             presence of a biopsy proven plasmacytoma and measurable disease as defined by any of
             the following: (a) immunoglobulin (Ig) G myeloma (serum monoclonal paraprotein
             [M-protein] level >=1.0 gram/deciliter [g/dL] or urine M-protein level >=200
             milligram[mg]/24 hours[hrs]; or (b) IgA, IgM, IgD, or IgE multiple myeloma (serum
             M-protein level >=0.5 g/dL or urine M-protein level >=200 mg/24 hrs); or (c) light
             chain multiple myeloma without measurable disease in serum or urine (serum
             immunoglobulin free light chain >=10 mg/dL and abnormal serum immunoglobulin kappa
             lambda free light chain ratio)

          -  Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status
             score of 0, 1, or 2

          -  Participants who are newly diagnosed and not considered for high-dose chemotherapy due
             to: being age >=65 years; or participants less than (<) 65 years with presence of
             important comorbid condition(s) likely to have a negative impact on tolerability of
             high dose chemotherapy with stem cell transplantation. Sponsor review and approval of
             participants below 65 years of age is required before randomization

          -  Women of childbearing potential must commit to either abstain continuously from sexual
             intercourse or to use 2 methods of reliable birth control simultaneously as deemed
             appropriate by the Investigator. Contraception must begin 4 weeks prior to dosing and
             must continue for 3 months after the last dose of daratumumab

          -  Man, who is sexually active with a woman of child-bearing potential must agree to use
             a latex or synthetic condom, even if he had a successful vasectomy, must agree to use
             an adequate contraception method as deemed appropriate by the Investigator, and must
             also agree to not donate sperm during the study and for 4 weeks after last dose of
             lenalidomide and 4 months after last dose of daratumumab

        Exclusion Criteria:

          -  Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of
             undetermined significance (presence of serum M-protein <3 g/dL; absence of lytic bone
             lesions, anemia, hypercalcemia, and renal insufficiency related to the M-protein), or
             smoldering multiple myeloma (asymptomatic multiple myeloma with absence of related
             organ or tissue impairment end organ damage)

          -  Participant 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

          -  Participant 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)

          -  Participant 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 4 days) of corticosteroids before treatment

          -  Participant has had radiation therapy within 14 days of randomization

          -  Participant has known chronic obstructive pulmonary disease (COPD) (defined as a
             forced expiratory volume in 1 second [FEV1] <50% of predicted normal), persistent
             asthma, or a history of asthma within the last 2 years (controlled intermittent asthma
             or controlled mild persistent asthma is allowed)

          -  Participants with known or suspected COPD must have a FEV1 test during Screening

          -  Participant is known to be seropositive for human immunodeficiency virus (HIV) or
             hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg] or
             antibodies to hepatitis B surface and core antigens [anti-HBs and anti-HBc,
             respectively]) or hepatitis C (anti-HCV antibody positive or HCV-ribonucleic acid
             [RNA] quantitation positive)