Multiple Myeloma
Conditions
Keywords
Multiple Myeloma (MM), Transplant ineligible, Newly diagnosed, Linvoseltamab, BCMA X CD3 bispecific antibody, CD38 antibody, Lenalidomide
Brief summary
This study is researching an experimental drug called linvoseltamab. The study is focused on participants with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplantation (transplant-ineligible). The main purpose of this study is to compare the effect and safety of linvoseltamab with the effect and safety of the standard treatment.
Interventions
DRUGLinvoseltamab
Administered per the protocol
DRUGDaratumumab
Administered per the protocol
DRUGLenalidomide
Administered per the protocol
DRUGDexamethasone
Administered per the protocol
Sponsors
European Myeloma Network B.V.
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants must have confirmed diagnosis of symptomatic MM per IMWG criteria. 2. Participants must not be considered a candidate for high-dose chemotherapy (HDT) and ASCT, as described in the protocol. 3. Participants must have measurable disease as defined in the protocol. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. 5. Participants must have clinical laboratory values within a prespecified range.
Exclusion criteria
1. International Myeloma Working Group Frailty Index of 2 with the exception of participants who have a score of 2 based on age alone. 2. Participants who defer transplant due to personal preference. 3. Participants with non-secretory MM, active plasma cell leukemia, known light-chain (AL) amyloidosis in the presence of a concurrent diagnosis of myeloma, any other form of amyloidosis, Waldenström macroglobulinemia, or known POEMS syndrome. 4. Any prior therapy for monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or MM, with the exception of: * focal radiation and/or * a short course of corticosteroids as defined in the protocol. 5. Participants who have received or are receiving any investigational agent or cell therapy with known or suspected activity against MM 6. Participants who have known central nervous system (CNS) or meningeal involvement with MM or known or suspected progressive multifocal leukoencephalopathy (PML), a history of a neurocognitive condition or CNS movement disorder, OR a history of seizure, transient ischemic attack (TIA), stroke or seizure within 12 months prior to study C1D1. 7. Participants who have uncontrolled intercurrent illness. 8. Known contraindications to the use of daratumumab or lenalidomide per local prescribing information. 9. History of allogeneic hematopoietic stem cell transplantation or solid organ transplant at any time. NOTE Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Minimal Residual Disease (MRD) | up to 11 years | Minimal Residual Disease (MRD) negative Complete Remission (CR) status at 10\^-5 per International Myeloma Working Group (IMWG) criteria |
| MRD negative CR status by BICR | up to 11 years | MRD negative CR status at 10\^-5 as determined by the Blinded Independent Central Review (BICR) |
| Progression Free Survival (PFS) per IMWG criteria | up to 11 years | defined as the time from the date of randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier, where disease progression is determined per IMWG criteria. |
| PFS as determined by BICR | up to 11 years | defined as the time from the date of randomization until the first occurrence of disease progression or death from any cause, whichever occurs earlier, where disease progression is determined per by BICR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | up to 11 years | Overall Survival (OS), measured from the date of from randomization to the date the subject's death |
| Objective Response (OR) of Complete Response (CR) | up to 11 years | To compare the proportion of patients who achieve an objective response per International Myeloma Working Group (IMWG) response criteria between the two study arms for Complete Response (CR) or better |
| OR of Very Good Partial Response (VGPR) | up to 11 years | To compare the proportion of patients who achieve an objective response per International Myeloma Working Group (IMWG) response criteria between the two study arms for VGPR or better |
| OR of Partial Response (PR) | up to 11 years | To compare the proportion of patients who achieve an objective response per International Myeloma Working Group (IMWG) response criteria between the two study arms for PR or better |
| Sustained MRD | up to 11 years | Sustained MRD negative CR (sMRD) at 10\^-5 per IMWG criteria |
| Duration of response (DOR) of stringent (s)CR | up to 11 years | duration of response to best overall response of stringent sCR, per IMWG response criteria |
| Duration of response (DOR) of CR | up to 11 years | duration of response to best overall response of CR, per IMWG response criteria |
| Duration of response (DOR) of VGPR | up to 11 years | duration of response to best overall response of VGPR, per IMWG response criteria |
| Duration of response (DOR) of PR | up to 11 years | duration of response to best overall response of PR, per IMWG response criteria |
| Time to response ≥CR | up to 11 years | Time from randomization to objective response (≥CR) as per IMWG response criteria |
| Time to response ≥VGPR | up to 11 years | Time from randomization to objective response (≥VGPR) as per IMWG response criteria |
| Time to response ≥PR | up to 11 years | Time from randomization to objective response (≥PR) as per IMWG response criteria |
| Disease progression | up to 11 years | Time to disease progression per IMWG response criteria |
| Incidence of TEAEs | up to 11 years | Incidence of treatment emergent adverse events (TEAEs) |
| Severity of TEAEs | up to 11 years | Severity of treatment emergent adverse events (TEAEs) |
| Serious Adverse Events | up to 11 years | Incidence of Serious Adverse Events (SAE) |
| Concentrations of linvoseltamab | up to 11 years | Concentrations of linvoseltamab in serum over time |
| Incidence antidrug antibodies | up to 11 years | Incidence of antidrug antibodies (ADAs) to linvoseltamab |
| Titer of ADA | up to 11 years | Titer of ADA to linvoseltamab |
| EORTC QLQ-C30 Global Health Status / Quality of Life | up to 11 years | Change in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) The EORTC QLQ-C30 is a 30-item validated questionnaire developed to measure patient-reported quality of life using one global health status/quality of life (GHS/QoL) scale, 5 functioning scales (physical, role, emotional, cognitive, and social) ranging from from 1 = "very poor" to 7 = "excellent" and 9 symptom scales/items (fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) among patients with cancer, ranging from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden. |
| EORTC QLQ-C30 Physical Functioning (PF) | up to 11 years | Change in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire functioning scale Physical Functioning (PF). PF scale consist of 5 items, ranging from from 1 = "not at all" to 4 = "very much" higher scores indicate higher ("better") level of functioning |
| EORTC QLQ-C30 Role Functioning (RF) | up to 11 years | Change in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire functioning scale Role Functioning (RF). RF scale consist of 2 items, ranging from from 1 = "not at all" to 4 = "very much" higher scores indicate higher ("better") level of functioning |
| EORTC QLQ-C30 Pain | up to 11 years | Change in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire symptom scale Pain. Pain scale consist of 2 items, ranging from from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden |
| EORTC QLQ-C30 Fatigue | up to 11 years | Change in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire symptom scale Fatigue. Fatigue scale consist of 3 items, ranging from from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden |
| EQ-5D-5L VAS | up to 11 years | Change in EuroQoL-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS) (EQ-5D-5L VAS). The EQ-5D-5L is a generic questionnaire that measures Health-Related Quality of Life (HRQoL) across 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) across 5 levels (1= no problems, 2= slight problems, 3= some problems, 4= severe problems and 5= extreme problems), higher scores indicate lower health states And a visual analogue scale (VAS). VAS scale ranging from 0 = "worst" to 100 = "best" higher score indicate higher health status |
Countries
Australia, Austria, Croatia, Czechia, Denmark, Estonia, Finland, Germany, Greece, Ireland, Italy, Netherlands, Norway, Portugal, Spain, Sweden, Switzerland, Turkey (Türkiye)
Contacts
CONTACTSilvia Villa
PRINCIPAL_INVESTIGATORRoberto Mina
A.O.U. Città della Salute e della Scienza di Torino
PRINCIPAL_INVESTIGATORClaudia Stege
Erasmus Medical Center
Outcome results
None listed