ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 8 for:    isatuximab Phase 3

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03319667
Recruitment Status : Recruiting
First Posted : October 24, 2017
Last Update Posted : November 9, 2018
Sponsor:
Information provided by (Responsible Party):
Sanofi

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), PFS in MRD negative patients, duration of response (DOR), PFS on next line of therapy (PFS2), overall survival (OS), overall response rate (ORR) (including crossover arm) 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)

Condition or disease Intervention/treatment Phase
Plasma Cell Myeloma Drug: Isatuximab SAR650984 Drug: Bortezomib Drug: Lenalidomide Drug: Dexamethasone Drug: Acetaminophen (paracetamol) or equivalent Drug: Ranitidine or equivalent Drug: Diphenhydramine or equivalent Phase 3

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 ± 4 days), a continuous treatment period and a crossover period (when applicable). The cycle duration is 28 ± 4 days during the continuous treatment and crossover periods.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 440 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel and crossover
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 7, 2017
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : January 2025


Arm Intervention/treatment
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
Drug: Isatuximab SAR650984

Pharmaceutical form: Solution for infusion

Route of administration: Intravenous (IV)


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


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
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


Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm
4-weeks cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone
Drug: Isatuximab SAR650984

Pharmaceutical form: Solution for infusion

Route of administration: Intravenous (IV)


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





Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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)

  12. 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)

  13. 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

  14. Immunogenicity [ Time Frame: Up to approximately 60 months after the FPI or scheduled assessment ]
    Levels of isatuximab anti-drug antibodies

  15. 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)

  16. 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

  17. 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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Symptomatic 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.
  • Asymptomatic 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03319667


Contacts
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-Us@sanofi.com

  Show 99 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03319667     History of Changes
Other Study ID Numbers: EFC12522
2017-002238-21 ( EudraCT Number )
U1111-1194-2121 ( Other Identifier: UTN )
First Posted: October 24, 2017    Key Record Dates
Last Update Posted: November 9, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
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/

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Diphenhydramine
Lenalidomide
Thalidomide
Bortezomib
Ranitidine
Acetaminophen
BB 1101
Promethazine
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents