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Clinical Benefit of SAR650984, Bortezomib, Lenalidomide and Dexamethasone Combination in NDMM Patients Not Eligible for Transplant (IMROZ)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03319667
Recruitment Status : Active, not recruiting
First Posted : October 24, 2017
Last Update Posted : August 4, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE September 18, 2017
First Posted Date  ICMJE October 24, 2017
Last Update Posted Date August 4, 2020
Actual Study Start Date  ICMJE December 7, 2017
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 19, 2017)
Progression free survival (PFS) [ Time Frame: Up to approximately 60 months after the first patient in (FPI) or scheduled assessment ]
PFS defined as the time from the date of randomization to the date of first documentation of progression disease (PD) as determined by the independent review committee (IRC) or the date of death from any cause, whichever occurs first
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 2, 2020)
  • Very good partial response (VGPR) or better rate [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Proportion of patients with stringent complete response (sCR), CR and VGPR as assessed by the IRC using the IMWG criteria
  • Minimal residual disease (MRD) negativity rate [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Proportion of patients for whom MRD measurement is negative
  • Complete response rate (CR) [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Proportion of patients with CR/sCR as assessed by the IRC using the IMWG criteria
  • Overall response rate (ORR) [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Proportion of patients with best overall response (BOR) recorded as sCR, CR, VGPR, or partial response (PR) as assessed by the IRC using the IMWG criteria
  • Time to progression (TTP) [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Defined as the time from randomization to date of first documentation of PD as assessed by the IRC using the IMWG criteria
  • Duration of response (DOR) [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Defined as the time from date of first IRC determined response to date of first IRC PD or death, whichever occurs first for patients achieving sCR, CR, VGPR, or PR
  • Time to first response (TT1R) [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Time from randomization to the first IRC determined response (PR or better) that is subsequently confirmed
  • Time to best response (TTBR) [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Defined as the time from randomization to the date of first occurrence of IRC determined best response (PR or better) that is subsequently confirmed
  • PFS on next line of therapy (PFS2) [ Time Frame: At 4 years after cutoff for primary PFS analysis ]
    Defined as the time from randomization to the date of first documentation of disease progression (as assessed by investigator) after initiation of further anti-myeloma treatment, or death from any cause, whichever occurs first
  • PFS in MRD negative patients [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Defined as the time from the date of randomization to the date of first documentation of PD or the date of death from any cause, whichever comes first in MRD negative patients
  • Overall survival (OS) [ Time Frame: At 4 years after cutoff for primary PFS analysis ]
    Defined as the time from the date of randomization to death from any cause
  • Adverse Events [ Time Frame: Up to 30 days after end of treatment (EOT) visit ]
    Treatment-emergent adverse events/serious adverse events (TEAEs/SAEs) including infusion associated reactions (IARs), second primary malignancies, laboratory parameters, vital signs, weight, ECOG PS, and findings from physical examination
  • Assessment of PK parameter: Ctrough [ Time Frame: Cycle 1 Day 8/Day 15/Day 29 (pre-dose) and Day 1 (pre-dose) of Cycle 2, 3, 4, 5, 6, 7, 8, 9 and 10 (Duration of each cycle for Cycles 1-4: 6 weeks; Duration of each cycle for Cycles 5-10: 4 weeks) ]
    Isatuximab: Pre-dose plasma isatuximab concentration (Ctrough)
  • Assessment of PK parameter: AUC [ Time Frame: Cycle 1 Day 1 to Day 29 ]
    Isatuximab: Cumulative area under the plasma isatuximab concentration versus time curve (AUC)
  • Assessment of PK parameter: CL [ Time Frame: Cycle 1 Day 1 to Cycle 10 Day 1 (Duration of each cycle for Cycles 1-4: 6 weeks; Duration of each cycle for Cycles 5-10: 4 weeks) ]
    Isatuximab: Clearance (CL) for linear non-specific elimination pathway
  • Immunogenicity [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Levels of isatuximab anti-drug antibodies
  • Patient reported outcome (PRO): QLQ-C30 [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Disease-specific HRQL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30)
  • PRO: QLQ-MY20 [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Disease- and treatment-related quality of life will be assessed using the EORTC myeloma module (QLQ-MY20) questionnaire
  • PRO: EQ-5D-5L [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Health state utility and health status will be assessed using the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)
Original Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2017)
  • Very good partial response (VGPR) or better rate [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Proportion of patients with CR and VGPR as assessed by the IRC using the IMWG criteria
  • Complete response rate (CR) [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Proportion of patients with CR as assessed by the IRC using the IMWG criteria
  • Minimal residual disease (MRD) negativity rate [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Proportion of patients with CR and VGPR and for whom MRD measurement is negative
  • Overall response rate (ORR) [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Proportion of patients with best overall response (BOR) recorded as CR, VGPR, or partial response (PR) as assessed by the IRC using the IMWG criteria
  • Time to progression (TTP) [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Defined as the time from randomization to date of first documentation of PD as assessed by the IRC using the IMWG criteria
  • Duration of response (DOR) [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Defined as the time from date of first IRC determined response to date of first IRC PD or death, whichever occurs first for patients achieving CR, VGPR, or PR
  • PFS on next line of therapy (PFS2) [ Time Frame: At 4 years after cutoff for primary PFS analysis ]
    Defined as the time from randomization to second objective PD, or death from any cause, whichever occurs first
  • PFS in MRD negative patients [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Defined as the time from the date of randomization to the date of first documentation of PD or the date of death from any cause, whichever comes first in MRD negative patients
  • Overall survival (OS) [ Time Frame: At 4 years after cutoff for primary PFS analysis ]
    Defined as the time from the date of randomization to death from any cause
  • Adverse Events [ Time Frame: Up to 30 days after end of treatment (EOT) visit ]
    Treatment-emergent adverse events/serious adverse events (TEAEs/SAEs) including infusion associated reactions (IARs), second primary malignancies, laboratory parameters, vital signs, weight, ECOG PS, and findings from physical examination
  • Assessment of PK parameter: Ctrough [ Time Frame: Cycle 1 Day 8/Day 15/Day 29 (pre-dose) and Day 1 (pre-dose) of Cycle 2, 3, 4, 5, 6, 7, 8, 9 and 10 (Duration of each cycle for Cycles 1-4: 6 weeks; Duration of each cycle for Cycles 5-10: 4 weeks) ]
    Isatuximab: Pre-dose plasma isatuximab concentration (Ctrough)
  • Assessment of PK parameter: AUC [ Time Frame: Cycle 1 Day 1 to Day 29 ]
    Isatuximab: Cumulative area under the plasma isatuximab concentration versus time curve (AUC)
  • Assessment of PK parameter: CL [ Time Frame: Cycle 1 Day 1 to Cycle 10 Day 1 (Duration of each cycle for Cycles 1-4: 6 weeks; Duration of each cycle for Cycles 5-10: 4 weeks) ]
    Isatuximab: Clearance (CL) for linear non-specific elimination pathway
  • Immunogenicity [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Levels of isatuximab anti-drug antibodies
  • Patient reported outcome (PRO): QLQ-C30 [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Disease-specific HRQL will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30)
  • PRO: QLQ-MY20 [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Disease- and treatment-related quality of life will be assessed using the EORTC myeloma module (QLQ-MY20) questionnaire
  • PRO: EQ-5D-5L [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Health state utility and health status will be assessed using the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Benefit of SAR650984, Bortezomib, Lenalidomide and Dexamethasone Combination in NDMM Patients Not Eligible for Transplant
Official Title  ICMJE A Phase 3 Randomized, Open-label, Multicenter Study Assessing the Clinical Benefit of Isatuximab (SAR650984) in Combination With Bortezomib (Velcade®), Lenalidomide (Revlimid®) and Dexamethasone Versus Bortezomib, Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma (NDMM) Not Eligible for Transplant
Brief Summary

Primary Objective:

To demonstrate the benefit of isatuximab (I) in combination with bortezomib (V), lenalidomide (R) and dexamethasone (d) in the prolongation of progression free survival (PFS) as compared with bortezomib, lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma (NDMM) not eligible for transplant.

Secondary Objectives:

  • To evaluate in both randomized arms: very good partial response (VGPR) or better rate as defined by the International Myeloma Working Group (IMWG) criteria, minimal residual disease (MRD) negativity rate in patients with complete response (CR) or VGPR, CR rate per IMWG criteria, time to progression (TTP) and overall by MRD status, PFS in MRD negative patients, duration of response (DOR) and overall by MRD status, time to first response (TT1R), time to best response (TTBR), PFS on next line of therapy (PFS2), overall survival (OS), overall response rate (ORR) per IMWG criteria (including crossover arm), safety (including crossover arm), and to assess disease-specific and generic health-related quality of life (HRQL)
  • To determine the pharmacokinetic (PK) profile of isatuximab in combination with bortezomib, lenalidomide, and dexamethasone (excluding crossover arm)
  • To evaluate the immunogenicity of isatuximab in patients receiving isatuximab (including crossover arm)
Detailed Description The duration of the study for each patient will include a screening period of up to 4 weeks, an induction period of 24 weeks (4 cycles with a duration of 42 ± 3 days), a continuous treatment period and a crossover period (when applicable). The cycle duration is 28 ± 3 days during the continuous treatment and crossover periods.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Parallel and crossover
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Plasma Cell Myeloma
Intervention  ICMJE
  • Drug: Isatuximab SAR650984

    Pharmaceutical form: Solution for infusion

    Route of administration: Intravenous (IV)

    Other Name: Sarclisa
  • Drug: Bortezomib

    Pharmaceutical form: Lyophilized powder for injection

    Route of administration: Intravenous/Subcutaneous

    Other Name: Velcade®
  • Drug: Lenalidomide

    Pharmaceutical form: Capsules

    Route of administration: Oral

    Other Name: Revlimid®
  • Drug: Dexamethasone

    Pharmaceutical form: Tablets, ampoules or vials for injection

    Route of administration: Oral/Intravenous

  • Drug: Acetaminophen (paracetamol) or equivalent

    Pharmaceutical form: Tablets

    Route of administration: Oral

  • Drug: Ranitidine or equivalent

    Pharmaceutical form: Solution for injection

    Route of administration: Intravenous

  • Drug: Diphenhydramine or equivalent

    Pharmaceutical form: Solution for injection

    Route of administration: Intravenous

Study Arms  ICMJE
  • Experimental: Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm
    1. Induction treatment with 4x6-week cycles with intravenous (IV) isatuximab + subcutaneous (SC) bortezomib + oral lenalidomide + IV or oral dexamethasone
    2. Continuous treatment with 4-week cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone
    Interventions:
    • Drug: Isatuximab SAR650984
    • Drug: Bortezomib
    • Drug: Lenalidomide
    • Drug: Dexamethasone
    • Drug: Acetaminophen (paracetamol) or equivalent
    • Drug: Ranitidine or equivalent
    • Drug: Diphenhydramine or equivalent
  • Active Comparator: Bortezomib/Lenalidomide/Dexamethasone = VRd arm
    1. Induction treatment with 4x6-week cycles with SC bortezomib + oral lenalidomide + IV or oral dexamethasone
    2. Continuous treatment with 4-week cycles with oral lenalidomide + IV or oral dexamethasone
    Interventions:
    • Drug: Bortezomib
    • Drug: Lenalidomide
    • Drug: Dexamethasone
  • Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm
    4-weeks cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone
    Interventions:
    • Drug: Isatuximab SAR650984
    • Drug: Lenalidomide
    • Drug: Dexamethasone
    • Drug: Acetaminophen (paracetamol) or equivalent
    • Drug: Ranitidine or equivalent
    • Drug: Diphenhydramine or equivalent
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 27, 2019)
475
Original Estimated Enrollment  ICMJE
 (submitted: October 19, 2017)
440
Estimated Study Completion Date  ICMJE January 2025
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria :

  • Multiple myeloma (IMWG criteria).
  • Newly diagnosed multiple myeloma not eligible for transplant due to age (≥ 65 years) or patients < 65 years with comorbidities impacting possibility of transplant.
  • Evidence of measurable disease.
  • Written informed consent.

Exclusion criteria:

  • Age < 18 years.
  • Prior treatment for multiple myeloma.
  • Any other prior or ongoing disease/health conditions incompatible with the study objectives.
  • Organ function values not met.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ( PS) > 2.
  • Hypersensitivity to the study medications.
  • Pregnant, breastfeeding, or woman of child bearing potential unwilling to use recommended contraception methods.
  • Male participants who disagree to follow the study contraceptive counseling.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   China,   Czechia,   Denmark,   France,   Germany,   Greece,   Italy,   Japan,   Lithuania,   Mexico,   New Zealand,   Poland,   Portugal,   Russian Federation,   Spain,   Sweden,   Taiwan,   Turkey,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03319667
Other Study ID Numbers  ICMJE EFC12522
2017-002238-21 ( EudraCT Number )
U1111-1194-2121 ( Other Identifier: UTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP