Cancer MedDRA version: 20.0 Level: PT Classification code 10035226 Term: Plasma cell myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Sanofi-aventis recherche & developpement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients must have a known diagnosis of multiple myeloma with evidence of measurable disease, as defined below: -> Serum M-protein =1 g/dL (=0.5 g/dL in case of IgA disease), AND/OR -> Urine M-protein =200 mg/24 hours, OR -> In the absence of measurable m-protein, serum immunoglobulin free light chain =10 mg/dL, and abnormal serum immunoglobulin kappa lambda free light chain ratio (1.65). - Patients must have received prior treatment with an IMiD (for =2 cycles or =2 months of treatment) and a proteasome inhibitor (for =2 cycles or =2 months of treatment). - Patients must have received at least 3 prior lines of therapy (Note: Induction therapy and stem cell transplant ± maintenance will be considered as one line) OR - Patients whose disease is double refractory to an IMID and a PI (disease progression has occurred while on or within 60 days from end of the treatment). - Patient must have achieved MR or better with any anti-myeloma therapy (ie, primary refractory disease is not eligible). - Patients must have a disease that is refractory to the most recent prior line therapy (disease progression has occurred while on treatment or within 60 days from end of the treatment). 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 26 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 44
Exclusion criteria
Exclusion criteria: - Prior exposure to isatuximab or participated clinical studies with isatuximab. - Prior exposure to any agent (approved or investigational) that blocks the PD-1/PD-L1 pathway. - Evidence of other immune related disease /conditions. - History of non-infectious pneumonitis requiring steroids or current pneumonitis; history of the thoracic radiation. - Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted. - Has allogenic haemopoietic stem cell (HSC) transplant. - Eastern Cooperative Oncology Group (ECOG) performance status (PS) >2. - Poor bone marrow reserve. - Poor organ function.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -To evaluate the safety and tolerability of the combination of Isatuximab (also known as SAR650984) and REGN2810 in patients with relapse/refractory multiple myeloma. -To evaluate the overall response rate of the combination of Isatuximab and REGN2810 in patients with RRMM.;Secondary Objective: -To evaluate the efficacy as assessed by clinical benefit rate (CBR), duration of response (DOR), time to response (TTR), progression free survival (PFS), and overall survival (OS). -To assess the pharmacokinetics (PK) of Isatuximab and REGN2810 when given in combination. -To assess the immunogenicity of isatuximab and REGN2810;Primary end point(s): 1 - Dose Limiting Toxicities (DLTs) DLTs are treatment-related adverse reactions in Cycle 1. Hematological DLT – Grade (G) 4 neutropenia >7 days; G 3 to 4 neutropenia with fever or documented infection; G 3 to 4 thrombocytopenia with bleeding requiring intervention. Non-hematological DLT - G 4 nonhematological AE; G =2 uveitis; G 3 non-hematological AE >3 days despite supportive care (with defined exceptions); Delay in initiation of the 2nd cycle >14 days for related laboratory abnormalities/AE. Other dose-limiting AE. 2 - Adverse events (AEs) and changes in laboratory tests and vital signs Number of patients with AEs and changes in laboratory tests and vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 Grade scaling 3 - Overall Response Rate (ORR) ORR is defined as the proportion of patients with complete response (CR) (including sCR [stringent complete response]), very good partial response (VGPR) and partial response (PR);Timepoint(s) of evaluation of this end point: 1 - Up to 4 weeks 2 - Up to 30 days following the last administration of study treatment for ongoing related AE, ongoing serious AE and new related AE until resolution or stabilization 3 - Up to 6 months from last patient in for primary efficacy analysis, and up to 12 months from last patien | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 - Clinical Benefit Rate (CBR) CBR is defined as the proportion of patients with CR (including sCR), VGPR, PR and minimalresponse (MR) 2 - Duration of Response (DOR) DOR is defined as the time from the date of the first response (=PR) that is subsequently confirmed to the date of first confirmed disease progression or death, whichever happens first 3 - Time to Response (TTR) TTR is defined as time from first study treatment administration to first response (=PR) that is subsequently confirmed 4 - Progression Free Survival (PFS) PFS is defined as time from the first study treatment administration to the date of first documentation of progressive disease that is subsequently confirmed or the date of death from any cause 5 - Overall Survival (OS) OS defined as the time from the first study treatment administration to death from any cause 6 - Assessment of PK parameter: partial AUC AUC is area under the drug concentration versus time curve 7 - Assessment of PK parameter: Cmax Cmax is maximum drug concentration observed 8 - Antibodies to isatuximab Levels of anti isatuximab antibodies in plasma samples will be determined 9 - Antibodies to REGN2810 Levels of anti REGN2810 antibodies in serum samples will be determined;Timepoint(s) of evaluation of this end point: 1 to 4: Up to 6 months from last patient in for primary efficacy analysis, and up to 12 months from LPI for the final analysis 5: Up to 12 months from LPI for the final analysis 6 and 7: Up to 4 weeks 8 and 9: Up to 12 months from LPI for the final analysis | — |
Countries
Canada, France, Hungary, United States
Outcome results
None listed