Multiple Myeloma
Conditions
Brief summary
The main purpose of this study is to see how well a new treatment ramantamig-D works compared to standard treatments that is either DVRd or DRd on progression-free survival (PFS; time until a participant's disease worsens) and 12-month minimal residue disease (MRD)-negative complete response (CR) rate (percentage of participants in whom cancer cells are not detected) in participants with newly diagnosed multiple myeloma (NDMM; an initial stage of blood cancer that forms in a type of white blood cells \[WBCs\] called plasma cells) for whom stem cell transplant is not planned as initial therapy.
Interventions
DRUGRamantamig
Ramantamig will be administered subcutaneously.
DRUGDaratumumab
Daratumumab will be administered subcutaneously.
DRUGLenalidomide
Lenalidomide will be administered orally.
DRUGBortezomib
Bortezomib will be administered subcutaneously or intravenously.
DRUGDexamethasone
Dexamethasone will be administered orally or intravenously.
Sponsors
Janssen Research & Development, LLC
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
* Documented diagnosis of multiple myeloma (MM) according to the IMWG diagnostic criteria * Not considered for high-dose chemotherapy with autologous stem cell transplantation (ASCT) due to: i. ineligible due to advanced age; or ii. ineligible due to presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT; or iii. deferral of high-dose chemotherapy with ASCT as initial treatment * Have an eastern cooperative oncology status (ECOG) performance status of 0 to 2 * Must sign an informed consent form (ICF) * Measurable disease at screening as assessed by central laboratory as defined in the protocol
Exclusion criteria
* Myeloma Frailty Score of greater than or equal to (\>=) 2 with the exception of participants who have a score of 2 based on age alone * Suspected or known allergies, hypersensitivity, intolerance or other contraindications to any trial intervention or its excipients * Had major surgery (for example, requiring general anesthesia) or had significant traumatic injury within 2 weeks prior to first dose or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the trial * Known active or prior CNS involvement or exhibits clinical signs of meningeal involvement of MM * Received any prior therapy(ies) for treatment of MM or smoldering myeloma, with the exception of emergency use of a short course of corticosteroids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to approximately 62 months | PFS is defined as the time from treatment assignment (that is, randomization in the trial) to confirmed progression of disease (PD) or death, whichever occurs first. |
| Percentage of Participants Achieving 12-Month Minimal Residual Disease (MRD)-Negative Complete Response CR | Up to 12 months | 12-month MRD-negative CR rate is defined as achieving MRD-negative status at the analysis time window of 12 months (+/-3 months), as determined by next-generation sequencing (NGS) with sensitivity of 10\^-5, prior to PD or subsequent antimyeloma therapy (including ASCT). Additionally, CR or better must be achieved any time from randomization up to and including 12+3 months, according to international myeloma working group (IMWG) criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with CR or Better | Up to 5 years | Percentage of participants achieving CR, or sCR prior to subsequent antimyeloma therapy in accordance with IMWG criteria during or after the trial intervention will be reported. |
| Percentage of Participants with Overall Response | Up to 5 years | Percentage of participants achieving PR or better prior to subsequent antimyeloma therapy in accordance with IMWG criteria during or after the trial intervention will be reported. |
| Percentage of Participants with Overall MRD-Negative CR | Up to 5 years | Percentage of participants who achieve MRD-negative status, as determined by NGS at any time point after randomization and prior to PD or subsequent antimyeloma therapy and who achieve CR or better will be reported. |
| Percentage of Participants with 12-Month Sustained MRD-Negative CR | Up to 5 years | Percentage of participants with confirmed CR or better who sustain MRD-negative status, as determined by NGS, for at least 12 months without any examination showing MRD-positive status or PD in between will be reported. |
| Progression Free Survival After Subsequent Therapy (PFS2) | Up to approximately 100 months | PFS2 is defined as the time interval between the date of randomization and date of event, which is defined as PD as assessed by investigator on the first subsequent line of antimyeloma therapy, or death from any cause, whichever occurs first. |
| Number of Participants with Adverse Events (AEs) | Up to approximately 100 months | An AE is any untoward medical occurrence in a clinical trial participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. |
| Overall Survival (OS) | Up to approximately 100 months | OS is defined as time from treatment assignment (that is, randomization in the trial) to date of death due to any cause. |
| Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) Scale Score | Baseline up to approximately 100 months | The MySIm-Q is a disease-specific PRO assessment complementary to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30). It includes 17 items with recall period of "7 days" and responses are reported on a 5-point verbal rating scale. Item responses are scored from 0 to 4. Higher scores indicate greater severity/impact. |
| Change from Baseline in HRQoL as Assessed by EORTC-QLQ-C30 Scale Score | Baseline up to approximately 100 months | The EORTC QLQ-C30 Version 3 includes 30 items that make up 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, and nausea/vomiting), and 5 single symptom items (dyspnea, insomnia, appetite loss, constipation, and diarrhea) and a single impact item (financial difficulties). The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms. |
| Change from Baseline in HRQoL as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Scale Score | Baseline up to approximately 100 months | The EQ-5D-5L is a self-administered, generic health status measure, consisting of a descriptive system and a visual analog scale (EQ-VAS). The EQ-5D-5L descriptive system covers 5 dimensions of health (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression), each with 5 levels of severity (no problems, slight problems, moderate problems, severe problems, and unable to perform or extreme problems) with higher scores indicating worse HRQoL. |
| Change from Baseline in HRQoL as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score | Baseline up to approximately 100 months | The PGI-S is a 2-item questionnaire that assesses severity of the participant's symptoms and impacts of their symptoms, respectively, on a 5-point verbal rating scale, at the time of completing the PRO measure. Score ranges from 1 (None) to 5 (Very Severe). Higher scores indicate greater severity. |
| Change from Baseline in HRQoL as Assessed by European Organization for Research and Treatment of Cancer Item List (EORTC IL) 46 | Baseline up to approximately 100 months | The EORTC IL46 consists of a single question that measures global impression of burden due to treatment-related symptoms. The response options range from "not at all" to "very much" on a 4 point scale where higher scores indicate more symptoms. |
| Percentage of Participants Achieving 24-Month Sustained MRD-Negative CR | Up to 5 years | 24-month sustained MRD-negative CR is defined as achieving confirmed CR or better while sustaining MRD-negative status for at least 24 months without any examination showing MRD positive status or PD in between. |
| Percentage of Participants with Tolerability to Ramantamig-D Measured Through Patient Reported Outcomes (PROs) | Up to approximately 100 months | Percentage of participants with tolerability to ramantamig-D measured through PROs will be reported. |
| Percentage of Participants with Very Good Partial Response (VGPR) or Better | Up to 5 years | Percentage of participants achieving VGPR, CR, or stringent complete response (sCR) prior to subsequent antimyeloma therapy in accordance with IMWG criteria during or after the trial intervention will be reported. |
Contacts
CONTACTStudy Contact
STUDY_DIRECTORJanssen Research & Development LLC Clinical trial
Janssen Research & Development, LLC
Outcome results
None listed