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Completed

NCT Number: 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

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Investigational Site Number : 250002, Nantes, France

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Lenalidomide

Drug

Pharmaceutical form: tablet Route of administration: oral

Other names: Revlimid

bortezomib

Drug

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

Other names: Velcade

Cyclophosphamide

Drug

Pharmaceutical form: tablet Route of administration: oral

Other names: Endoxan

Dexamethasone

Drug

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

isatuximab SAR650984

Drug

Pharmaceutical form: solution for infusion Route of administration: intravenous

Other names: Sarclisa

Primary outcomes

  1. Assessment of dose-limiting toxicities (DLTs) in VCDI cohort

    Time frame: Up to 6 weeks per treated patient

  2. Overall response rate (VCDI)

    Time frame: Up to 34 weeks of treatment (induction phase)

  3. Complete response rate (VCDI)

    Time frame: Up to 34 weeks of treatment (induction phase)

  4. Complete response rate (VRDI)

    Time frame: Up to 104 weeks of treatment (induction and maintenance phase) in VRDI part A and part B cohorts

Secondary outcomes

  1. 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

    Time frame: VCDI: Up to approximately 106 weeks, VRDI Part A and Part B: Up to approximately 104 weeks

  2. Overall response rate (VRDI)

    Time frame: Up to 104 weeks of treatment (induction and maintenance phase) in VRDI part A and part B cohorts

  3. Infusion duration

    Time frame: VRDI Part B: Up to 104 weeks of treatment

  4. Assessment of PK parameter: Partial area under the serum concentration time curve (AUC)

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

  5. Assessment of PK parameter: Maximum observed concentration (Cmax)

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

  6. Levels of human antidrug antibodies (ADA)

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

  7. Duration of response - time

    Time frame: VCDI and VRDI: Until treatment discontinuation by the last patient

  8. Progression-free survival for VCDI

    Time frame: VCDI: 30 months after LPI

  9. Progression-free survival for VRDI

    Time frame: VRDI Part A and Part B: 24 months after LPI

  10. MRD negativity rate

    Time frame: Up to 3 years of treatment (induction and maintenance phase) in VRDI part A and part B cohorts

Sponsors and collaborators

Lead sponsor

Sanofi

Industry

Registry information

Official study 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

Important dates

Study start
2015
Primary completion
2022
Study completion
2024
First posted
Jul 31, 2015
Registry last updated
Jan 29, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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