Plasma Cell Myeloma
Conditions
Keywords
Anti-CD38 monoclonal antibody
Brief summary
Primary Objectives: * VCDI cohort: * To determine the maximum tolerated dose (MTD) and recommended dose (RD) of SAR650984 isatuximab when administered in combination with bortezomib (Velcade®) , cyclophosphamide, and dexamethasone (VCDI) based on the dose-limiting toxicity(ies) (DLTs) observed in patients with newly diagnosed multiple myeloma non-eligible for transplantation * To evaluate safety and preliminary efficacy (overall response rate and complete response rate) of isatuximab administered at the selected dose in combination with bortezomib based regimin VCDI according to IMWG criteria. * VRDI Part A cohort and Part B cohort: * To evaluate the preliminary efficacy (complete response \[CR\] rate) of isatuximab administered at the selected dose in combination with bortezomib based regimen: VRDI, (bortezomib, lenalidomide, dexamethasone) according to IMWG criteria in adult patients with newly diagnosed MM non eligible for transplantation or no intent for immediate transplantation. Secondary Objectives: * VCDI cohort: * To characterize the overall safety profile of SAR650984 in combination with VCD regimen, including cumulative toxicities. * To characterize the pharmacokinetic (PK) profile of SAR650984/isatuximab and each combination drug in VCDI regimen. * To evaluate the immunogenicity of SAR650984 in combination treatments. * To evaluate the preliminary efficacy of VCDI regimen in terms of duration of response and progression-free survival. * To assess the relationship between clinical effects (adverse event \[AE\] and/or tumor response) and CD38 receptor density. * VRDI Part A cohort and Part B cohort: * To characterize the overall safety profile of isatuximab in combination with VRD regimen. * To evaluate the infusion duration (only applicable for VRDI Part B cohort) * To characterize the PK profile of isatuximab and each combination drug in VRDI regimen. * To evaluate the immunogenicity of isatuximab in combination treatments. * To evaluate the preliminary efficacy of VRDI regimen in terms of ORR, DOR, and PFS. * To evaluate the impact of M protein measurement without isatuximab interference (via the SEBIA HYDRASHIFT 2/4 isatuximab IFE test) on CR and BOR assessment. * To assess the relationship between clinical effects (AE and/or tumor response) and CD38 receptor density (only applicable for VRDI Part A cohort). * To assess MRD negativity rate in patients achieving a CR or VGPR and explore correlation with clinical outcome.
Detailed description
The duration of the study for an individual patient will include: * A period to assess eligibility (screening or baseline period) of up to 3 weeks for VCDI cohort, up to 28 days for VRDI cohort; * for patients in the VCDI cohort: a treatment period including up to 12 induction treatment cycles (50-week duration). * for patients in the VRDI cohort: a treatment period including up to 4 induction cycles (24 week duration). * Following induction, both cohorts have maintenance periods consisting of 4 week cycles until progression, unacceptable AE, or patient willingness to discontinue and an end-of-treatment visit at least 30 days following the last administration of treatment. * Patients that discontinue therapy for reasons other than progression will have follow-up visits until progression or until the patient receives another anticancer therapy, whichever is earlier.
Interventions
DRUGlenalidomide
Pharmaceutical form: tablet Route of administration: oral
DRUGbortezomib
Pharmaceutical form: lyophilized powder for subcutaneous injection Route of administration: subcutaneous
DRUGcyclophosphamide
Pharmaceutical form: tablet Route of administration: oral
DRUGdexamethasone
Pharmaceutical form: tablet or solution for infusion Route of administration: oral or intravenous
Pharmaceutical form: solution for infusion Route of administration: intravenous
Sponsors
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed patients with measurable multiple myeloma defined as at least one of the following: * Serum M protein ≥1 g/dL (≥10 g/L). * Urine M protein ≥200 mg/24 hours. * Serum free light chain (sFLC) assay: involved free light chain assay ≥10 mg/dL (≥100 mg/L) and an abnormal sFLC ratio (\<0.26 or \>1.65). * Patients with ultra-high risk smoldering multiple myeloma fulfilling the International Myeloma Working Group criteria are eligible. * Patient is not eligible for transplant. * Patient with no intent for immediate transplant as per investigator's decision are also eligible for VRDI Part B cohort only.
Exclusion criteria
* Eastern Cooperative Oncology Group performance status \>2. * Poor bone marrow reserve. * Poor organ function. 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 |
|---|---|
| Assessment of dose-limiting toxicities (DLTs) in VCDI cohort | Up to 6 weeks per treated patient |
| Overall response rate (VCDI) | Up to 34 weeks of treatment (induction phase) |
| Complete response rate (VCDI) | Up to 34 weeks of treatment (induction phase) |
| Complete response rate (VRDI) | Up to 104 weeks of treatment (induction and maintenance phase) in VRDI part A and part B cohorts |
Secondary
| Measure | Time frame |
|---|---|
| Assessment of PK parameter: Maximum observed concentration (Cmax) | VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks |
| Levels of human antidrug antibodies (ADA) | VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks |
| Duration of response - time | VCDI and VRDI: Until treatment discontinuation by the last patient |
| Number of patients with adverse events (AEs), clinically significant changes in laboratory tests and vital signs according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 grade scaling | VCDI: Up to approximately 106 weeks, VRDI Part A and Part B: Up to approximately 104 weeks |
| Progression-free survival for VRDI | VRDI Part A and Part B: 24 months after LPI |
| MRD negativity rate | Up to 3 years of treatment (induction and maintenance phase) in VRDI part A and part B cohorts |
| Progression-free survival for VCDI | VCDI: 30 months after LPI |
| Overall response rate (VRDI) | Up to 104 weeks of treatment (induction and maintenance phase) in VRDI part A and part B cohorts |
| Infusion duration | VRDI Part B: Up to 104 weeks of treatment |
| Assessment of PK parameter: Partial area under the serum concentration time curve (AUC) | VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks |
Countries
France, Germany, Italy, Spain
Outcome results
None listed