Relapsed/refractory multiple myeloma (RRMM) MedDRA version: 25.0 Level: LLT Classification code 10086466 Term: Relapsed/refractory multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: isatuximab
Product Code: SAR650984
Pharmaceutical Form: Solution for injection
INN or Proposed INN: isatuximab
Current Sponsor code: SAR650984
Concentration unit: mg/ml milligram(s)/mill
Sponsors
Sanofi-aventis recherche & developpement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Participants must have a documented diagnosis of multiple myeloma (MM) -Participants with measurable disease defined as at least one of the following: --Serum M-protein =0.5 g/dL measured using serum protein immunoelectrophoresis and/or --Urine M-protein =200 mg/24 hours measured using urine protein immunoelectrophoresis and/or --Serum free light chain (FLC) assay: Involved FLC assay =10 mg/dL (=100 mg/L) and an abnormal serum FLC ratio (1.65). -Participant with relapsed and/or refractory MM with at least 1 prior line of therapy and no more than 3 prior lines of therapy. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and either is not a female of childbearing potential (FCBP) or agrees to practice complete abstinence or use approved contraception methods. Male participants agree to practice true abstinence or agree to use approved contraception methods while receiving study treatment, during dose interruptions and at least 3 months following study treatment discontinuation, even if has undergone a successful vasectomy. Capable of giving signed informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 38 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 37
Exclusion criteria
Exclusion criteria: -Primary refractory MM defined as participants who have never achieved at least a minimal response (MR) with any treatment during the disease course -Participants with prior anti-CD38 treatment are excluded if: a) Progression on or within 60 days after end of anti-CD38 mAb treatment or failure to achieve at least MR to treatment (ie, refractory to anti-CD38) with a washout period inferior to 9 months before the first isatuximab administration or, b) Intolerant to the anti-CD38 previously received -Prior treatment with carfilzomib -Known history of allergy to captisol (a cyclodextrin derivative used to solubilize carfilzomib), prior hypersensitivity to sucrose, histidine (as base and hydrochloride salt), polysorbate 80, or any of the components (active substance or excipient) of study treatment that are not amenable to premedication with steroids, or intolerance to arginine and Poloxamer 188 that would prohibit further treatment with these agents -Uncontrolled or active infection with hepatitis A, B, and C virus; known acquired immunodeficiency syndrome (AIDS)-related illness; active primary amyloid light chain (AL) amyloidosis -Any severe acute or chronic medical condition which could impair the ability of the participant to participate in the study or interfere with interpretation of study results (eg, systemic infection unless specific anti-infective therapy is employed) or participant unable to comply with the study procedures. The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • The primary objective is to describe the efficacy of isatuximab SC in combination with carfilzomib and dexamethasone (Kd);Secondary Objective: • To evaluate patient preference for the On Body Delivery System (OBDS) versus manual administration of isatuximab SC • To assess the safety of isatuximab SC in combination with Kd • To assess the local tolerability of isatuximab SC in combination with Kd • To characterize the pharmacokinetics (PK) of isatuximab in combination with Kd after manual and OBDS administration • To evaluate the efficacy of isatuximab SC in combination with Kd • To assess the potential immunogenicity of isatuximab SC • To assess disease-specific and generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility, and health status;Primary end point(s): Overall response rate (ORR). ORR defined as the proportion of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to the 2016 International Myeloma Working Group (IMWG) criteria assessed by Independent Review Committee (IRC).;Timepoint(s) of evaluation of this end point: 6 months after the Last Participant In (LPI) i.e., approximately 16 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Proportion of participants preferring OBDS over manual administration of isatuximab SC at Day 15 of Cycle 6. Patient preference for method of administration defined as the proportion of participants preferring OBDS over manual administration of isatuximab SC at Day 15 of Cycle 6 using the patient experience and satisfaction questionnaire version 2 (PESQ v2). 2. Incidence rate of infusion reactions (IRs). 3. Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and changes in laboratory parameters. 4. Incidence rate of injection site reactions (ISRs). 5. PK concentration: trough plasma concentration (Ctrough). Blood samples will be collected for measurement of isatuximab concentrations. 6. Proportion of participants with sCR, CR, VGPR, and PR according to the 2016 IMWG criteria assessed by IRC. 7. Duration of response (DOR). DOR defined as time from date of first IRC-determined response for participants achieving PR or better to first documentation of progressive disease (PD) determined by IRC or death, whichever occurred first. 8. Time to first response (TT1R). TT1R defined as time from randomization to first IRC determined response (PR or better) that is subsequently confirmed. 9. Time to best response (TTBR). TTBR defined as time from randomization to first occurrence of IRC determined best response (PR or better) that is subsequently confirmed. 10. Progression free survival (PFS). PFS defined as time from the date of randomization to the date of first documentation of PD as determined by IRC or the date of death from any cause, whichever comes first. 11. Overall survival (OS). OS defined as time from the date of randomization to death from any cause. 12. Incidence of participants with anti-drug antibodies (ADA) against isatuximab. 13. Patient Expectations Questionnaire at Baseline (PEQ-BL v2) with isatuximab administered subcutaneously. PEQ-BL v2 is a participant assessed questionnaire. It | — |
Countries
Australia, Brazil, Czechia, Czech Republic, Greece, Japan, Portugal, Switzerland
Contacts
Public ContactClinical Study Unit
sanofi-aventis, s.r.o.
Outcome results
None listed