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

NCT02513186 | Completed Phase 1

• 3 other identifiers: TCD13983U1111-1154-61022014-001251-23
• Study Type: interventional
• Target: 90
• Locations: 4 countries
• Sites: 12

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.

Conditions

Plasma Cell Myeloma

Keywords

Anti-CD38 monoclonal antibody

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (10)

• 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

• 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

• Assessment of PK parameter: Maximum observed concentration (Cmax)

  VCDI: Up to approximately 42 weeks, VRDI: Up to approximately 48 weeks

Study Arms (1)

Isatuximab

EXPERIMENTAL

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.

Drug: lenalidomide; Drug: bortezomib; Drug: cyclophosphamide; Drug: dexamethasone; Drug: isatuximab SAR650984

Interventions

lenalidomide DRUG

Pharmaceutical form: tablet Route of administration: oral

Also known as: Revlimid

Isatuximab

bortezomib DRUG

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

Also known as: Velcade

Isatuximab

cyclophosphamide DRUG

Pharmaceutical form: tablet Route of administration: oral

Also known as: Endoxan

Isatuximab

dexamethasone DRUG

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

Isatuximab

isatuximab SAR650984 DRUG

Pharmaceutical form: solution for infusion Route of administration: intravenous

Also known as: Sarclisa

Isatuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (12)

Investigational Site Number : 250002

Nantes, 44093, France

Location

Investigational Site Number : 250003

Pierre-Bénite, 69495, France

Location

Investigational Site Number : 250001

Toulouse, 31059, France

Location

Investigational Site Number : 276003

Berlin, 12200, Germany

Location

Investigational Site Number : 276002

Leipzig, 04103, Germany

Location

Investigational Site Number : 380003

Milan, 20132, Italy

Location

Investigational Site Number : 380002

Roma, 00161, Italy

Location

Investigational Site Number : 380001

Torino, 10126, Italy

Location

Investigational Site Number : 724004

Santander, Cantabria, 39008, Spain

Location

Investigational Site Number : 724001

Pamplona, Navarre, 31008, Spain

Location

Investigational Site Number : 724003

Madrid, 28041, Spain

Location

Investigational Site Number : 724002

Salamanca, 37007, Spain

Location

Related Publications (1)

• 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.

  PMID: 37316728 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; Bortezomib; Cyclophosphamide; Dexamethasone; isatuximab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2015
• First Posted: July 31, 2015
• Study Start: September 30, 2015
• Primary Completion: January 28, 2022
• Study Completion: January 22, 2024
• Last Updated: January 29, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share

Locations

IT (3); ES (4); DE (2); FR (3)