Multiple Myeloma
Conditions
Brief summary
The purpose of this study is to evaluate the rate of response (how effectively treatment is working) with signs of potential cure at 5 years after the start of induction treatment. This is defined as a composite of sustained (at least 2 years) minimal residual disease (MRD) negativity with complete response/stringent complete response (CR/sCR) and a positron emission tomography/computed tomography (PET/CT) scan that does not show any signs of cancer at 5 years. MRD negativity and CR/sCR is defined as no detectable signs of remaining cancer cells after the treatment. This study will also characterize how well the treatments administered work in the study through progression-free survival (PFS). PFS is defined as the length of time during and after the treatment of a disease, that a participant lives with the disease, but it does not get worse.
Interventions
DRUGCilta-cel
Cilta-cel infusion will be administered intravenously.
DRUGTalquetamab
Talquetamab will be administered subcutaneously.
DRUGDaratumumab
Daratumumab will be administered subcutaneously as a part of DVRd induction and Tal-D or Tec-D consolidation.
DRUGTeclistamab
Teclistamab will be administered subcutaneously.
DRUGBortezomib
Bortezomib will be administered subcutaneously as a part of induction.
DRUGLenalidomide
Lenalidomide will be administered orally as a part of induction.
DRUGDexamethasone
Dexamethasone will be administered orally as a part of induction.
DRUGCyclophosphamide
Cyclophosphamide will be administered intravenously as a part of conditioning regimen.
DRUGFludarabine
Fludarabine will be administered intravenously as a part of conditioning regimen.
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 70 Years
Healthy volunteers
No
Inclusion criteria
* Participants with documented new diagnosis of multiple myeloma (MM) according to international myeloma working group (IMWG) diagnostic criteria and with no prior myeloma-directed therapy * Participants must have standard-risk MM (stage I and II) based on revised International Staging System (R-ISS) * Participants must be considered fit (score equals to \[=\] 0) or intermediate-fit (score=1) according to IMWG Frailty Index assessment (based on the Charlson Comorbidity Index, the Katz Activity of Daily Living and the Lawson Instrumental Activities of Daily Living) * Measurable disease defined as: Serum monoclonal paraprotein (M-protein) level greater than or equal to (\>=) 1.0 gram per deciliter (g/dL) (\>=10 gram per liter \[g/L\] for institutions using alternative units) or urine M-protein level \>= 200 milligrams per 24 hours (mg/24 hours); Light chain MM without measurable disease in the serum or the urine: Serum immunoglobulin free light chain \>=10 milligrams per deciliter (mg/dL) (\>=100 mg/L for institutions using alternative units) and abnormal serum immunoglobulin kappa lambda free light chain ratio * Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
Exclusion criteria
* Any ongoing myelodysplastic syndrome or B-cell malignancy (other than MM). Any history of malignancy, other than MM, which is considered at high risk of recurrence requiring systemic therapy * Peripheral neuropathy or neuropathic pain of Grade \>= 2, as defined by National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 * Known active or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of MM * Stroke or seizure within 6 months of signing the informed consent form (ICF) * Plasma cell leukemia at the time of diagnosis or any time thereafter through apheresis (\>= 5 percent \[%\] circulating plasma cells in peripheral blood smears), Waldenstrom macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes(POEMS) syndrome, or primary amyloid light chain amyloidosis with associated organ dysfunction * Presence of high-risk disease features: (a) Cytogenetic high risk lesions by MM fluorescence in situ hybridization (FISH) including deletion 17p (del\[17p\])/, t(4;14), t(14;16), amplification 1q (amp\[1q21\]) (\>= 4 copies); (b) Presence of 1 or more extramedullary plasmacytomas * Seropositive for human immunodeficiency virus (HIV)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Response with Curative Potential | Up to 5 years | Rate of Response with curative potential is defined as the percentage of participants with a composite of durable (at least 2 years) minimal residual disease (MRD) (10\^-5) negativity with complete response/stringent complete response (CR/sCR) by serology and negative positron emission tomography/computed tomography (PET/CT) imaging at 5-years after start of induction therapy. This includes: negative imaging at 5-year landmark time; MRD-negative status (at 10\^-5) in 2 bone marrow examinations that are a minimum of 2 years apart; response of CR or better per the International Myeloma Working Group (IMWG) criteria; no examination showing MRD-positive status or relapse from CR in between assessments. |
| Progression Free Survival (PFS) Rate at 3-Year | At 3-year | PFS is defined as the time from the date of randomization to either progressive disease (PD), according to the IMWG response criteria, or death, whichever occurs first. |
| PFS Rate at 5-Year | At 5-year | PFS is defined as the time from the date of randomization to either PD, according to the IMWG response criteria, or death, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR; Partial response [PR] or better) | Up to 5 years | ORR (PR or better) is defined as the percentage of participants with best overall response of PR or better according to IMWG response criteria. |
| CR or Better Rate | Up to 5 years | Rate of CR or better is defined as the percentage of participants with best overall response of CR or better according to IMWG response criteria. |
| Very Good Partial Response (VGPR) or Better Rate | Up to 5 years | Rate of VGPR or better is defined as the percentage of participants with best overall response of VGPR or better rate according to IMWG response criteria. |
| Duration of Response (DOR) | Up to 5 years | DOR is calculated among responders (with a PR or better response) from the date of initial documented response (PR or better) to the date of first documented evidence of PD as defined according to IMWG criteria or death due to any cause, whichever occurs first. |
| Time to First Response (TTR) | Up to 5 years | Time to response (that is, time to first response) is defined as the time between the date of randomization and the first efficacy evaluation that the participant has met all criteria for PR or better based on the computerized algorithm per IMWG criteria for those who had PR or better as their best response. |
| Duration of CR or Better Response | Up to 5 years | Duration of CR or better response is calculated among responders (with a CR or better response) from the date of initial documented response CR or better to the date of first documented evidence of PD as defined according to IMWG criteria or death due to any cause, whichever occurs first. |
| Time to First CR or Better Response | Up to 5 years | Time to first CR or better response is defined as the time between the date of randomization and the first efficacy evaluation that the participant has met all criteria for CR or better based on the computerized algorithm per IMWG criteria. |
| PFS on next line therapy (PFS2) | Up to 5 years | PFS2 is defined as time from randomization to progression on the next line of therapy or death, whichever comes first. |
| Overall Survival (OS) | Up to 5 years | OS is measured from the date of randomization to the date of death due to any cause. |
| MRD-negative CR Rate | Up to 5 years | MRD-negative CR is defined as the percentage of participants who achieved both CR or better and MRD negativity at a threshold of 10\^-5 and 10\^-6. MRD-negative CR rate will be evaluated at the first occurrence from induction treatment initiation for participants per IMWG criteria. |
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) by Severity | Up to 5 years | An Adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment. Severity of TEAEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (death). Grade 1= mild, Grade 2= moderate, Grade 3= severe, Grade 4= life-threatening and Grade 5= death related to adverse events. |
| Change from baseline in Health-related quality of life (HRQoL) (symptoms and functioning) using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 item instrument (EORTC-QLQ-C30) | Up to 5 years | Change from baseline in participants' HRQoL (symptoms and functioning) as assessed by EORTC-QLQ-C30 will be reported. The EORTC-QLQ-C30 includes 30 items in 5 functional scales (physical, role, emotional, cognitive, social), 1 global health status scale, 3 symptom scales (pain, fatigue, nausea/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties). The recall period is 1 week ("past week") and responses are reported using a verbal rating scale. 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. |
Countries
Australia, Brazil, Germany, Spain, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed