Multiple Myeloma (MM)
Conditions
Keywords
Autologous Stem Cell Transplantation (ASCT), Transplant-Eligible, Linvoseltamab, Newly Diagnosed Multiple Myeloma (NDMM), High-dose chemotherapy, Bortezomib (V), Lenalidomide (R), Daratumumab (D), bortezomib (V), lenalidomide (R), dexamethasone (d) (DVRd)
Brief summary
This study is focused on participants with Newly Diagnosed Multiple Myeloma (NDMM) who are eligible for high dose chemotherapy followed by Autologous Stem Cell Transplantation (ASCT). This study is evaluating a drug called linvoseltamab in combination with standard therapies for multiple myeloma called bortezomib (V) and lenalidomide (R). This combination is abbreviated as Linvo-VR. The aim of this study is to compare how well Linvo-VR, with and without ASCT, treats myeloma to how well the current standard of care regimen for NDMM treats myeloma. That current standard of care regimen includes the drugs daratumumab (D), bortezomib (V), lenalidomide (R), and dexamethasone (d). This combination is referred to as DVRd. The study is also evaluating if Linvo-VR treats myeloma well enough that ASCT is no longer needed with the first myeloma treatments. The study is looking at several other research questions, including: * What side effects may happen from taking linvoseltamab * How much linvoseltamab is in the blood at different times * Whether the body makes antibodies against the linvoseltamab (which could make the drug less effective or could lead to side effects)
Interventions
DRUGLinvoseltamab
Administered per the protocol
DRUGBortezomib
Administered per the protocol
DRUGLenalidomide
Administered per the protocol
DRUGDaratumumab
Administered per the protocol
DRUGDexamethasone
Administered per the protocol
Sponsors
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
Key Inclusion Criteria: 1. Participants must have a histologically or cytologically confirmed diagnosis of multiple myeloma, which requires the presence of clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma, and at least one other criteria as defined by the SLiM (\>=60%, Light chains I/U \>10, Magnetic resonance imaging \>1 focal lesion) CRAB (Calcium elevation, Renal insufficiency, Anemia, Bone disease) criteria 2. Participants must have measurable disease, as defined in the protocol 3. Participants must be considered eligible for high-dose chemotherapy (melphalan) and ASCT per local standard guidelines 4. Eastern Cooperative Oncology Group (ECOG) performance status ≤2 5. Must be willing to defer ASCT Key
Exclusion criteria
1. Any prior therapy for Monoclonal Gammopathy of Undetermined Significance (MGUS), Monoclonal Gammopathy of Renal Significance (MGRS), Smoldering Multiple Myeloma (SMM), or MM, with the exception of those defined in the protocol 2. Participants who have received or are receiving any investigational agent or cell therapy with known or suspected activity against MM (or another plasma cell disorder), or those whose AEs due to agents administered earlier (such as radiation and/or corticosteroids) have not recovered to a severity of grade 0 or grade 1 3. Participants with non-secretory MM, diagnosis of plasma cell leukemia (\>20% circulating plasma cells), symptomatic amyloidosis (including myeloma associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes). 4. 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), or stroke within 12 months prior to study randomization 5. Another malignancy besides MM that is progressive or has required treatment in the 3 years preceding randomization with the exceptions defined in the protocol NOTE: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Treatment-Emergent Adverse Events (TEAEs) | Up to day 112 | Phase 2 |
| Severity of TEAEs | Up to day 112 | Phase 2 |
| Achievement of Complete Response or better (≥CR) per International Myeloma Working Group (IMWG) criteria | Up to day 112 | Phase 2 |
| Minimal Residual Disease (MRD) negative CR at 10^-5 per IMWG criteria | Up to 12 months | Phase 3 |
| Progression Free Survival (PFS) per IMWG | Up to 5 years | Phase 3 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of TEAEs | Up to 3.5 years | Phase 2 |
| Severity of TEAEs | Up to 3.5 years | Phase 2 |
| Occurrence of Serious Adverse Events (SAEs) | Up to 3.5 years | Phase 2 |
| Severity of SAEs | Up to 3.5 years | Phase 2 |
| Occurrence of Cytokine Release Syndrome (CRS) | Up to day 30 | Phase 2 |
| Severity of CRS | Up to day 30 | Phase 2 |
| Occurrence of Cell-Associated Neurotoxicity Syndrome (ICANS) | Up to day 30 | Phase 2 |
| Severity of ICANS | Up to day 30 | Phase 2 |
| Achievement of objective response [Partial Response or better (≥PR)] per IMWG criteria | Up to 5 years | — |
| Time to ≥PR per IMWG criteria | Up to 5 years | — |
| Time to Very Good Partial Response or better (≥VGPR) per IMWG criteria | Up to 5 years | — |
| Time to ≥CR per IMWG criteria | Up to 5 years | — |
| Achievement of MRD negative (at 10^-5 sensitivity) CR per IMWG criteria | Up to 5 years | — |
| Duration Of Response (DOR) of ≥PR per IMWG criteria | Up to 5 years | — |
| Duration of ≥VGPR per IMWG criteria | Up to 5 years | — |
| Duration of ≥CR per IMWG criteria | Up to 5 years | — |
| PFS per IMWG criteria | Up to 5 years | — |
| Second PFS (PFS2) per IMWG criteria | Up to 5 years | — |
| Overall Survival (OS) | Up to 5 years | — |
| Concentrations of total linvoseltamab in serum | Up to 5 years | — |
| Occurrence of SAEs | Up to 5 years | Phase 3 |
| Occurrence of second primary malignancies | Up to 5 years | Phase 3 |
| Change from baseline in Global Health Status (GHS) per European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) | Up to 5 years | Phase 3 The EORTC QLQ-C30 is a 30-item validated questionnaire developed to measure patient-reported Quality of Life (QoL). For GHS, scores range from 1 = "very poor" to 5 = "excellent" with higher scores indicating better functioning and positive changes from baseline indicate improvement. |
| Change from baseline in physical functioning per EORTC QLQ-C30 | Up to 5 years | Phase 3 The EORTC QLQ-C30 is a validated 30-item questionnaire designed to measure patient-reported quality of life. Physical functioning is scored from 1 'very poor' to 5 'excellent,' with higher scores indicating better functioning; positive changes from baseline indicate improvement. |
| Change from baseline in role functioning per EORTC QLQ-C30 | Up to 5 years | Phase 3 The EORTC QLQ-C30 is a validated 30-item questionnaire designed to measure patient-reported quality of life. Role functioning is scored from 1 'very poor' to 5 'excellent,' with higher scores indicating better functioning; positive changes from baseline indicate improvement. |
| Change from baseline in pain per EORTC QLQ-C30 | Up to 5 years | Phase 3 The EORTC QLQ-C30 is a validated 30-item questionnaire designed to measure patient-reported quality of life. Pain is scored from 1 = "not at all" to 9 = "very much". Higher scores indicate higher symptom burden. |
| Change from baseline in fatigue per EORTC QLQ-C30 | Up to 5 years | Phase 3 The EORTC QLQ-C30 is a validated 30-item questionnaire designed to measure patient-reported quality of life. Fatigue is scored from1 = "not at all" to 9 = "very much". Higher scores indicate higher symptom burden. |
| Change from baseline in disease symptoms per EORTC QLQ- Multiple Myeloma Module 20 (MY20) | Up to 5 years | Phase 3 The EORTC QLQ-MY20 is a self-administered instrument to assess QoL in persons with MM. This 20-item questionnaire includes 6 items for disease symptoms. A high score for a symptom scale/item represents a high level of symptomatic problem. |
| Change from baseline in treatment side effects per EORTC QLQ-MY20 | Up to 5 years | Phase 3 The EORTC QLQ-MY20 is a self-administered instrument to assess QoL in persons with MM. This 20-item questionnaire includes 10 items for treatment side effects. A high score for a symptom scale/item represents a high level of symptomatic problem. |
| Change from baseline in body image per EORTC QLQ-MY20 | Up to 5 years | Phase 3 The EORTC QLQ-MY20 is a self-administered instrument to assess QoL in persons with MM. This 20-item questionnaire includes 1 item for treatment body image. A high score for a symptom scale/item represents a high level of symptomatic problem. |
| Change from baseline in future perspective per EORTC QLQ-MY20 | Up to 5 years | Phase 3 The EORTC QLQ-MY20 is a self-administered instrument to assess QoL in persons with MM. This 20-item questionnaire includes 3 items for treatment future perspective. A high score for a symptom scale/item represents a high level of symptomatic problem. |
| Change from baseline in EuroQoL-5 Dimensions 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) | Up to 5 years | Phase 3 The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: "no problems", "slight problems", "moderate problems", "severe problems" and "extreme problems". The EQ VAS records the participant's self-rated health on a vertical visual analogue scale where the endpoints are labeled "Best imaginable health state" and "Worst imaginable health state". |
| Time to definitive deterioration in GHS per EORTC QLQ-C30 | Up to 5 years | Phase 3 |
| Time to definitive deterioration in physical functioning per EORTC QLQ-C30 | Up to 5 years | Phase 3 |
| Time to definitive deterioration in role functioning per EORTC QLQ-C30 | Up to 5 years | Phase 3 |
| Time to definitive deterioration in pain per EORTC QLQ-C30 | Up to 5 years | Phase 3 |
| Time to definitive deterioration in fatigue per EORTC QLQ-C30 | Up to 5 years | Phase 3 |
| Time to definitive deterioration in disease symptoms per EORTC QLQ-MY20 | Up to 5 years | Phase 3 |
| Time to definitive deterioration in treatment side effects per EORTC QLQ-MY20 | Up to 5 years | Phase 3 |
| Time to definitive deterioration in body image per EORTC QLQ-MY20 | Up to 5 years | Phase 3 |
| Time to definitive deterioration in future perspective per EORTC QLQ-MY20 | Up to 5 years | Phase 3 |
| Time to definitive deterioration in EQ-5D-5L VAS | Up to 5 years | Phase 3 |
| Time to first improvement in GHS per EORTC QLQ-C30 | Up to 5 years | Phase 3 |
| Time to first improvement in physical functioning per EORTC QLQ-C30 | Up to 5 years | Phase 3 |
| Time to first improvement in role functioning per EORTC QLQ-C30 | Up to 5 years | Phase 3 |
| Time to first improvement in pain per EORTC QLQ-C30 | Up to 5 years | Phase 3 |
| Time to first improvement in fatigue per EORTC QLQ-C30 | Up to 5 years | Phase 3 |
| Time to first improvement in disease symptoms per EORTC QLQ-MY20 | Up to 5 years | Phase 3 |
| Time to first improvement in treatment side effects per EORTC QLQ-MY20 | Up to 5 years | Phase 3 |
| Time to first improvement in body image per EORTC QLQ-MY20 | Up to 5 years | Phase 3 |
| Time to first improvement in future perspective per EORTC QLQ-MY20 | Up to 5 years | Phase 3 |
| Time to first improvement in EQ-5D-5L VAS | Up to 5 years | Phase 3 |
| Proportion with clinically meaningful improvement in GHS per EORTC QLQ-C30 | Up to 5 years | Phase 3 |
| Proportion with clinically meaningful improvement in physical functioning per EORTC QLQ-C30 | Up to 5 years | Phase 3 |
| Proportion with clinically meaningful improvement in role functioning per EORTC QLQ-C30 | Up to 5 years | Phase 3 |
| Proportion with clinically meaningful improvement in pain per EORTC QLQ-C30 | Up to 5 years | Phase 3 |
| Proportion with clinically meaningful improvement in fatigue per EORTC QLQ-C30 | Up to 5 years | Phase 3 |
| Proportion with clinically meaningful improvement in disease symptoms per EORTC QLQ-MY20 | Up to 5 years | Phase 3 |
| Proportion with clinically meaningful improvement in treatment side effects per EORTC QLQ-MY20 | Up to 5 years | Phase 3 |
| Proportion with clinically meaningful improvement in body image per EORTC QLQ-MY20 | Up to 5 years | Phase 3 |
| Proportion with clinically meaningful improvement in future perspective per EORTC QLQ-MY20 | Up to 5 years | Phase 3 |
| Proportion of clinically meaningful improvement in EQ-5D-5L VAS | Up to 5 years | Phase 3 |
| Mean proportion of time with high side effect bother as measured by Functional Assessment of Cancer Therapy (FACIT)- Item Global Population 5 (GP5) | Up to 5 years | Phase 3 FACIT-Item GP5 will be used to assess the patient-reported impact of treatment toxicity that uses a single item "I am bothered by side effects of treatment" on a 5-point scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much). |
| Proportion of patients with high side effect bother as measured by FACIT- Item GP5 | Up to 5 years | Phase 3 |
| Occurrence of Anti-Drug Antibody (ADA) to linvoseltamab in serum | Up to 5 years | Phase 3 |
| Magnitude of ADA to linvoseltamab in serum | Up to 5 years | Phase 3 |
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed