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: 1. 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). 2.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 measurabl. Measurable disease, as assessed by central laboratory, defined by any of the following: - 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 - IgA, IgM, IgD, or IgE multiple myeloma (serum Mprotein level >=0.5 g/dL or urine Mprotein level >=200 mg/24 hrs); or - 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) 3.Newly diagnosed and not considered candidate for high-dose chemotherapy with SCT due to: ? Being age =65 years, OR ? In subjects 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 =30 mL/min (for lenalidomide dose adjustment for subjects with creatinine clearance 30-50 mL/min. Creatinine clearance can be calculated using the Cockcroft-Gault formula; or for subjects with over- or underweight, creatinine clearance may be measured from a 24-hours urine collection using the formula h) corrected serum calcium =14 mg/dL (=3.5 mM/L); or free ionized calcium =6.5 mg/dL (=1.6 mM/L) 6. Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for subjects participating in clinical studies. Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device [IUD], hormonal [progesterone-only birth control pills or injections or partner's vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin 4 weeks prior to dosing and must continue for 3 months after the last dose of daratumumab. Reliable contraception is ind
Exclusion criteria
Exclusion criteria: 1.Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma. Monoclonal gammopathy of undetermined significance is defined by presence of serum M-protein 470 msec 12. Subject has known allergies, hypersensitivity, or intolerance to corticos
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