Plasma Cell Myeloma
Conditions
Keywords
Anti-CD38 monoclonal antibody
Brief summary
Primary Objective: -To demonstrate the benefit of isatuximab in combination with bortezomib, lenalidomide, and dexamethasone in the prolongation of progression free survival (PFS) as compared to bortezomib, lenalidomide, and dexamethasone, in participants with newly diagnosed multiple myeloma (NDMM) not eligible for transplant. Secondary Objectives: * To evaluate in both randomized (isatuximab, bortezomib, lenalidomide and dexamethasone combination (IVRd) and bortezomib, lenalidomide and dexamethasone combination (VRd)) arms: * Complete response (CR) rate, as defined by the International Myeloma Working Group (IMWG) criteria. * Minimal residual disease (MRD) negativity rate in participants with CR. * Very good partial response or better rate, as defined by the IMWG criteria. * Overall survival (OS). * To evaluate the overall response rate (ORR) as per IMWG criteria. * To evaluate the time to progression (TTP) overall and by MRD status. * To evaluate PFS by MRD status. * To evaluate the duration of response (DOR) overall and by MRD status. * To evaluate time to first response (TT1R). * To evaluate time to best response (TTBR). * To evaluate progression-free survival on next line of therapy (PFS2). * To evaluate the sustained MRD negativity \>12 months rate. * To evaluate safety. * To determine the pharmacokinetic (PK) profile of isatuximab in combination with bortezomib, lenalidomide, and dexamethasone (IVRd arm only). * To evaluate the immunogenicity of isatuximab in participants receiving isatuximab (IVRd and crossover arms). * To assess disease-specific and generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility, and health status.
Detailed description
The duration of the study for each participant will include a screening period of up to 4 weeks, an induction period of 24 weeks (4 cycles with a duration of 42 ± 3 days), a continuous treatment period and a crossover period (when applicable). The cycle duration is 28 ± 3 days during the continuous treatment and crossover periods.
Interventions
Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV)
DRUGBortezomib
Pharmaceutical form: Lyophilized powder for injection Route of administration: Subcutaneous
DRUGLenalidomide
Pharmaceutical form: Capsules Route of administration: Oral
DRUGDexamethasone
Pharmaceutical form: Tablets, ampoules or vials for injection Route of administration: Oral/Intravenous
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Parallel and crossover
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Inclusion criteria : * Multiple myeloma (IMWG criteria). * Newly diagnosed multiple myeloma not eligible for transplant due to age (≥ 65 years) or participants \< 65 years with comorbidities impacting possibility of transplant. * Evidence of measurable disease. * Written informed consent.
Exclusion criteria
* Age \< 18 years. * Prior treatment for multiple myeloma. * Any other prior or ongoing disease/health conditions incompatible with the study objectives. * Organ function values not met. * Eastern Cooperative Oncology Group (ECOG) Performance Status ( PS) \> 2. * Hypersensitivity to the study medications. * Pregnant, breastfeeding, or woman of child bearing potential unwilling to use recommended contraception methods. * Male participants who disagree to follow the study contraceptive counseling. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) | Up to approximately 100 months after the First Participant In (FPI) | Defined as the time from the date of randomization to the date of first documentation of progression disease (PD) as determined by the independent review committee (IRC) or the date of death from any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate (CR) | Up to approximately 100 months after the FPI | Defined as the proportion of participants with CR and stringent complete response (sCR) as assessed by the IRC using the IMWG criteria. |
| Minimal residual disease (MRD) negativity rate for participants with CR | Up to approximately 100 months after the FPI | Proportion of participants with CR for whom MRD measurement is negative |
| Very good partial response (VGPR) or better rate | Up to approximately 100 months after the FPI | Proportion of participants with sCR, CR and VGPR as assessed by the IRC using the International Myeloma Working Group (IMWG) criteria |
| Overall response rate (ORR) | Up to approximately 100 months after the FPI assessment | Proportion of participants with best overall response (BOR) recorded as sCR, CR, VGPR, or partial response (PR) as assessed by the IRC using the IMWG criteria |
| Time to progression (TTP) | Up to approximately 100 months after FPI | Defined as the time from randomization to date of first documentation of PD as assessed by the IRC using the IMWG criteria |
| Duration of response (DOR) | Up to approximately 100 months after the FPI | Defined as the time from date of first IRC determined response to date of first IRC PD or death, whichever occurs first for participants achieving sCR, CR, VGPR, or PR |
| Time to first response (TT1R) | Up to approximately 100 months after the FPI | Time from randomization to the first IRC determined response (PR or better) that is subsequently confirmed |
| Time to best response (TTBR) | Up to approximately 100 months after the FPI | Defined as the time from randomization to the date of first occurrence of IRC determined best response (PR or better) that is subsequently confirmed |
| Overall survival (OS) | Up to approximately 110 months after the FPI | Defined as the time from the date of randomization to death from any cause |
| PFS in MRD negative participants | Up to approximately 100 months after the FPI | Defined as the time from the date of randomization to the date of first documentation of PD or the date of death from any cause, whichever comes first in MRD negative participants |
| Sustained MRD negativity ≥12 months rate | Up to approximately 100 months after the FPI | Defined as the proportion of participants with the maintenance of MRD negativity confirmed ≥12 months apart with no MRD positive test in between. |
| Adverse Events | Up to 30 days after end of treatment (EOT) visit | Treatment-emergent adverse events/serious adverse events (TEAEs/SAEs) including infusion associated reactions (IARs), second primary malignancies, laboratory parameters, vital signs, weight, ECOG PS, and findings from physical examination |
| Assessment of PK parameter: Ctrough | Cycle 1 Day 8/Day 15/Day 29 (pre-dose) and Day 1 (pre-dose) of Cycle 2, 3, 4, 5, 6, 7, 8, 9 and 10 (Duration of each cycle for Cycles 1-4: 6 weeks; Duration of each cycle for Cycles 5-10: 4 weeks) | Isatuximab: Pre-dose plasma isatuximab concentration (Ctrough) |
| Immunogenicity | Up to approximately 100 months after the FPI | Presence of anti-drug antibodies against isatuximab |
| participants reported outcome (PRO): QLQ-C30 | Up to approximately 100 months after the FPI | Disease-specific HRQL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30) |
| PRO: QLQ-MY20 | Up to approximately 100 months after the FPI | Disease- and treatment-related quality of life will be assessed using the EORTC myeloma module (QLQ-MY20) questionnaire |
| PRO: EQ-5D-5L | Up to approximately 100 months after the FPI | Health state utility and health status will be assessed using the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L) |
| PFS on next line of therapy (PFS2) | Up to approximately 110 months after the FPI | Defined as the time from randomization to the date of first documentation of disease progression (as assessed by investigator) after initiation of further anti-myeloma treatment, or death from any cause, whichever occurs first |
Countries
Australia, Belgium, China, Czechia, Denmark, France, Germany, Greece, Italy, Japan, Lithuania, Mexico, New Zealand, Poland, Portugal, Russia, Spain, Sweden, Taiwan, Turkey (Türkiye), United States
Outcome results
None listed