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

NCT ID: NCT02513186

Last Updated: 2024-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2024-01-22

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.

Conditions

Plasma Cell Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Isatuximab

VCDI cohort: Isatuximab (escalating dose) + bortezomib + cyclophosphamide + dexamethasone (VCDI): Induction phase will be 50 weeks (12 cycles). The duration of a cycle will be 42 days (6 weeks) for Cycle 1 (C1) and 28 days (4 weeks) for subsequent cycles. The duration of a cycle of the maintenance phase will be 28 days (4 weeks). After C12, isatuximab will be administered at its initial assigned dose and dexamethasone once every 28 days.

VRDI cohort parts A and B: Isatuximab + bortezomib + dexamethasone + lenalidomide (VRDI): Induction phase will be 24 weeks (4 cycles at 6 weeks/cycle). The duration of a cycle of the maintenance phase will be 28 days (4 weeks). Maintenance therapy may continue until disease progression, unacceptable AE or patient willingness to discontinue.

VRDI Part A: Enrollment to begin after the VCDI cohort is completed.

VRDI Part B: Enrollment to begin after the VRDI part A is completed.

Group Type: EXPERIMENTAL

lenalidomide

Intervention Type: DRUG

Pharmaceutical form: tablet Route of administration: oral

bortezomib

Intervention Type: DRUG

Pharmaceutical form: lyophilized powder for subcutaneous injection Route of administration: subcutaneous

cyclophosphamide

Intervention Type: DRUG

Pharmaceutical form: tablet Route of administration: oral

dexamethasone

Intervention Type: DRUG

Pharmaceutical form: tablet or solution for infusion Route of administration: oral or intravenous

isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form: solution for infusion Route of administration: intravenous

Interventions

lenalidomide

Pharmaceutical form: tablet Route of administration: oral

Intervention Type: DRUG

bortezomib

Pharmaceutical form: lyophilized powder for subcutaneous injection Route of administration: subcutaneous

Intervention Type: DRUG

cyclophosphamide

Pharmaceutical form: tablet Route of administration: oral

Intervention Type: DRUG

dexamethasone

Pharmaceutical form: tablet or solution for infusion Route of administration: oral or intravenous

Intervention Type: DRUG

isatuximab SAR650984

Pharmaceutical form: solution for infusion Route of administration: intravenous

Intervention Type: DRUG

Other Intervention Names

Revlimid; Velcade; Endoxan; Sarclisa

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number : 250002

Nantes, , France

Investigational Site Number : 250003

Pierre-Bénite, , France

Investigational Site Number : 250001

Toulouse, , France

Investigational Site Number : 276003

Berlin, , Germany

Investigational Site Number : 276002

Leipzig, , Germany

Investigational Site Number : 380003

Milan, , Italy

Investigational Site Number : 380002

Roma, , Italy

Investigational Site Number : 380001

Torino, , Italy

Investigational Site Number : 724004

Santander, Cantabria, Spain

Investigational Site Number : 724001

Pamplona, Navarre, Spain

Investigational Site Number : 724003

Madrid, , Spain

Investigational Site Number : 724002

Salamanca, , Spain

Countries

France; Germany; Italy; Spain

References

Ocio EM, Perrot A, Bories P, San-Miguel JF, Blau IW, Karlin L, Martinez-Lopez J, Wang SY, Bringhen S, Marcatti M, Mateos MV, Rodriguez-Otero P, Oliva S, Nogai A, Le Roux N, Dong L, Mace S, Gassiot M, Fitzmaurice T, Oprea C, Moreau P. Efficacy and safety of isatuximab plus bortezomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma ineligible/with no immediate intent for autologous stem cell transplantation. Leukemia. 2023 Jul;37(7):1521-1529. doi: 10.1038/s41375-023-01936-7. Epub 2023 Jun 14.

Reference Type: DERIVED

PMID: 37316728 (View on PubMed)

Other Identifiers

U1111-1154-6102

Identifier Type: REGISTRY

Identifier Source: secondary_id

2014-001251-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TCD13983

Identifier Type: -

Identifier Source: org_study_id