NCT02513186

Study of Isatuximab Combined With Bortezomib + Cyclophosphamide + Dexamethasone (VCD) and Bortezomib + Lenalidomide + Dexamethasone (VRD) in Newly Diagnosed Multiple Myeloma (MM) Non Eligible for Transplant or No Intent for Immediate Transplantation

A Dose Escalation, Safety, Pharmacokinetic, Pharmacodynamic and Preliminary Efficacy Study of SAR650984 (Isatuximab) Administered Intravenously in Combination With Bortezomib - Based Regimens in Adult Patients With Newly Diagnosed Multiple Myeloma Non Eligible for Transplantation or No Intent for Immediate Transplantation

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 90 (actual)
• Sponsor: Sanofi · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Plasma Cell Myeloma

Interventions

Type	Name	Description
DRUG	lenalidomide	Pharmaceutical form: tablet Route of administration: oral
DRUG	bortezomib	Pharmaceutical form: lyophilized powder for subcutaneous injection Route of administration: subcutaneous
DRUG	cyclophosphamide	Pharmaceutical form: tablet Route of administration: oral
DRUG	dexamethasone	Pharmaceutical form: tablet or solution for infusion Route of administration: oral or intravenous
DRUG	isatuximab SAR650984	Pharmaceutical form: solution for infusion Route of administration: intravenous

Timeline

• Start date: 2015-09-30
• Primary completion: 2022-01-28
• Completion: 2024-01-22
• First posted: 2015-07-31
• Last updated: 2024-01-29

Locations

12 sites across 4 countries: France, Germany, Italy, Spain