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

Plasma Cell Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02513186
• Other study ID #: TCD13983
• Secondary ID: U1111-1154-61022
• Status: Completed
• Phase: Phase 1
• Start date: September 30, 2015
• Est. completion date: January 22, 2024

Study information

• Verified date: January 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: January 22, 2024
• Est. primary completion date: January 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Plasma Cell Myeloma

Intervention

Drug:
• lenalidomide
Pharmaceutical form: tablet Route of administration: oral
• bortezomib
Pharmaceutical form: lyophilized powder for subcutaneous injection Route of administration: subcutaneous
• cyclophosphamide
Pharmaceutical form: tablet Route of administration: oral
• dexamethasone
Pharmaceutical form: tablet or solution for infusion Route of administration: oral or intravenous
• isatuximab SAR650984
Pharmaceutical form: solution for infusion Route of administration: intravenous

Locations

Country	Name	City	State
France	Investigational Site Number : 250002	Nantes Cedex 01
France	Investigational Site Number : 250003	Pierre Benite
France	Investigational Site Number : 250001	TOULOUSE Cedex 9
Germany	Investigational Site Number : 276003	Berlin
Germany	Investigational Site Number : 276002	Leipzig
Italy	Investigational Site Number : 380003	Milano
Italy	Investigational Site Number : 380002	Roma
Italy	Investigational Site Number : 380001	Torino
Spain	Investigational Site Number : 724003	Madrid
Spain	Investigational Site Number : 724001	Pamplona	Navarra
Spain	Investigational Site Number : 724002	Salamanca
Spain	Investigational Site Number : 724004	Santander	Cantabria

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of dose-limiting toxicities (DLTs) in VCDI cohort		Up to 6 weeks per treated patient
Primary	Overall response rate (VCDI)		Up to 34 weeks of treatment (induction phase)
Primary	Complete response rate (VCDI)		Up to 34 weeks of treatment (induction phase)
Primary	Complete response rate (VRDI)		Up to 104 weeks of treatment (induction and maintenance phase) in VRDI part A and part B cohorts
Secondary	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
Secondary	Overall response rate (VRDI)		Up to 104 weeks of treatment (induction and maintenance phase) in VRDI part A and part B cohorts
Secondary	Infusion duration		VRDI Part B: Up to 104 weeks of treatment
Secondary	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
Secondary	Assessment of PK parameter: Maximum observed concentration (Cmax)		VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks
Secondary	Levels of human antidrug antibodies (ADA)		VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks
Secondary	Duration of response - time		VCDI and VRDI: Until treatment discontinuation by the last patient
Secondary	Progression-free survival for VCDI		VCDI: 30 months after LPI
Secondary	Progression-free survival for VRDI		VRDI Part A and Part B: 24 months after LPI
Secondary	MRD negativity rate		Up to 3 years of treatment (induction and maintenance phase) in VRDI part A and part B cohorts