Multiple myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Sponsors
Janssen-Cilag International N.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subject must be at least 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place). -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 [Mprotein] level >=1.0 gram/deciliter [g/dL] or urine Mprotein level >=200 milligram[mg]/24 hours[hrs]; or (b) IgA, IgM, IgD, or IgE multiple myeloma (serum Mprotein level >=0.5 g/dL or urine Mprotein 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 highdose chemotherapy with SCT due to: being age >=65 years; or participants less than (=65 years) yes F.1.3.1 Number of subjects for this age range 37
Exclusion criteria
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 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 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 had radiation therapy within 14 days of randomization - Participant has had plasmapheresis within 28 days of randomization. -Participant is exhibiting clinical signs of meningeal involvement of multiple myeloma - Participant has 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 subjects suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal. - Participant has had known moderate or severe persistent asthma within the last 2 years or currently has uncontrolled asthma of any classification (controlled intermittent asthma or controlled mild persistent asthma are allowed in the study ) - Participants with known or suspected COPD or asthma must have a FEV1 test during Screening -Participant is known to be seropositive for history of human immunodeficiency virus (HIV) or known to have active hepatitis B or hepatitis C
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective : The primary objective is to compare the efficacy of daratumumab when combined with lenalidomide and dexamethasone (DRd) to that of lenalidomide and dexamethasone (Rd), in terms of progression-free survival (PFS) in subjects with newly diagnosed myeloma who are not candidates for high dose chemotherapy and autologous stem cell transplant;Secondary Objective: -To evaluate clinical outcomes including: Time to disease progression (TTP) CR rate MRD negativity rate PFS2 (defined as time from randomization to progression on the next line of therapy or death, whichever comes first) Overall survival Time to next treatment Stringent CR (sCR) rate Overall response rate (partial response [PR] rate or better) Proportion of subjects who achieve very good partial response (VGPR) or better Time to response Duration of response -To evaluate the clinical efficacy of daratumumab combination with Rd in high-risk molecular subgroups -To evaluate treatment effects on patient reported outcomes and heath economic/resource utilization -To assess the safety and tolerability of daratumumab when administered in combination with Rd. - To assess the pharmacokinetics of daratumumab in combination with Rd. - To assess the immunogenicity of daratumumab in Arm B subjects and the immunogenicity of rHuPH20 in subjects receiving daratumumab SC.;Primary end point(s): Progression-free Survival (PFS);Timepoint(s) of evaluation of this end point: From baseline for the duration of disease follow-up, with an expected average of 40 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1-Time to Disease Progression (TTP) 2-Percentage of Participants With Stringent Complete Response (sCR) 3-Percentage of Participants With Complete response (CR) 4-Progression-Free Survival on Next Line of Therapy (PFS2) 5-Percentage of Participants With Negative Minimal Residual Disease (MRD) 6-Time To Next Treatment 7-Percentage of Participants With Overall Response (OR) 8-Percentage of Participants With Very Good Partial Response (VGPR) or Better Response 9-Duration of Response (DR) 10-Overall Survival (OS)Time 11-European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score 12-Euro Quality of Life (EQ-5D-5L) Health State Profile Utility Score 13-Time to response;Timepoint(s) of evaluation of this end point: 1,2,3,4,6,7, 8 ,9 , 13- From baseline for the duration of disease followup, with an expected average of 40 months 5- From baseline up to 18 months after confirmed CR, with an expected average of 24 months 10- Baseline up to 5 years after last participant is randomized 11 and 12- From baseline up to 16 weeks after disease progression, with an expected average of 44 months | — |
Countries
Australia, Austria, Belgium, Canada, Denmark, France, Germany, Ireland, Israel, Italy, Netherlands, New Zealand, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Registry group
Janssen-Cilag International N.V.
Outcome results
None listed