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: - Participant must have documented multiple myeloma satisfying the calcium elevation, renal insufficiency, anemia, and bone abnormalities (CRAB) diagnostic criteria, monoclonal plasma cells in the bone marrow greater than or equal to 10 percent (%) or presence of a biopsy proven plasmacytoma, and measurable secretory disease, as assessed by the central laboratory, and defined in protocol . - Participants who are newly diagnosed and not considered candidate for high-dose chemotherapy with stem cell transplantation (SCT) due to: being age >=65 years, or in participants =65 years) yes F.1.3.1 Number of subjects for this age range 640
Exclusion criteria
Exclusion criteria: - Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma - Participant has a diagnosis of Waldenstrom’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 stem cell transplantation (SCT) for multiple myeloma, with the exception of an emergency use of a short course of corticosteroids before treatment - Participant has peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the national cancer institute common terminology criteria for adverse events (NCI CTCAE) Version 4 - Participant has a history of malignancy (other than multiple myeloma) within 3 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 3 years) - Participant has any concurrent medical or psychiatric condition or disease (example 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to determine if the addition of daratumumab to VMP will prolong PFS compared with VMP.;Secondary Objective: The secondary objectives are: ? To determine if the addition of daratumumab to VMP will improve clinical outcome as measured by: ? Time to disease progression (TTP) ? CR rate ? Minimal residual disease (MRD) negativity rate ? PFS2 (defined as time from randomization to progression on the next line of therapy or death, whichever comes first) ? Time to next treatment ? Overall response rate (partial response [PR] or better) ? Stringent CR (sCR) rate ? Very good partial response (VGPR) or better rate ? Time to response ? Duration of response ? Overall survival To assess patient reported outcomes and heath economic/resource utilization ? To determine the pharmacokinetics and immunogenicity of daratumumab in all subjects and the immunogenicity of recombinant human hyaluronidase PH20 (rHuPH20) in subjects receiving daratumumab SC ? To assess the safety and tolerability of daratumumab when administered in combination with VMP Please see protocol for a full list of objectives. ;Primary end point(s): The primary endpoint is Progression-free Survival (PFS), which is defined as the duration from the date of randomization to either progressive disease or death, whichever comes first. Disease progression will be determined according to the IMWG criteria. For subjects who have not progressed and are alive, data will be censored at the last disease evaluation before the start of any subsequent antimyeloma therapy. Relapse from CR by positive immunofixation or trace amount of M-protein is not considered to be progressive disease and is not included in the PFS calculation. As the superiority of daratumumab combined with VMP over VMP alone with respect to PFS was established at the second interim analysis, the interim PFS analysis will serve as the primary PFS analysis, which otherwise was to occur when approximately 360 PFS events had b | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Time to disease progression (TTP) is defined as the time from the date of randomization to the date of first documented evidence of PD, as defined in the IMWG criteria. For subjects who have not progressed, data will be censored at the date of the disease evaluation before the start of any subsequent anti-myeloma therapy. - CR rate, defined as the percentage of subjects achieving CR, as defined by: - Negative immunofixation of serum and urine, and - Disappearance of any soft tissue plasmacytomas, and - <5% PCs in bone marrow - For those subjects with negative or low SPEP (=0.2 g/L) and suspected daratumumab interference on immunofixation, a reflex assay using anti-idiotype antibody will be utilized to confirm daratumumab interference and rule out false positive immunofixation. Subjects who have confirmed daratumumab interference, but meet all other clinical criteria for CR or sCR, will be considered CR/sCR. - MRD negativity rate, defined as the proportion of subjects who have negative MRD at any time point after the date of randomization. - Progression-free Survival on Next line of Therapy (PFS2), defined as the time from randomization to progression on the next line of treatment or death, whichever comes first. Disease progression will be based on investigator judgment. Subjects who are still alive and not yet progressed on the next line of treatment will be censored on the last date of follow-up. - Time to next treatment, defined as the time from randomization to the start of the next-line treatment. - Overall response rate (ORR), defined as the proportion of subjects who achieve PR or better, according to the IMWG criteria, during or after the study treatment. - sCR rate, defined as the percentage of subjects achieving CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry. - Proportion of subjects who achieve VGPR | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Croatia, Czechia, Czech Republic, Georgia, Germany, Greece, Hungary, Italy, Japan, North Macedonia, Poland, Portugal, Romania, Russian Federation, Serbia, Spain, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Registry group
Janssen-Cilag International N.V.
Outcome results
None listed