Clinical Benefit of SAR650984, Bortezomib, Lenalidomide and Dexamethasone Combination in NDMM Patients Not Eligible for Transplant (IMROZ)
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| ClinicalTrials.gov Identifier: NCT03319667 |
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Recruitment Status :
Active, not recruiting
First Posted : October 24, 2017
Last Update Posted : April 8, 2024
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Sponsor:
Sanofi
Information provided by (Responsible Party):
Sanofi
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Brief Summary:
Primary Objective:
-To demonstrate the benefit of isatuximab in combination with bortezomib, lenalidomide, and dexamethasone in the prolongation of progression free survival (PFS) as compared to bortezomib, lenalidomide, and dexamethasone, in patients with newly diagnosed multiple myeloma (NDMM) not eligible for transplant.
Secondary Objectives:
- To evaluate in both randomized (isatuximab, bortezomib, lenalidomide and dexamethasone combination (IVRd) and bortezomib, lenalidomide and dexamethasone combination (VRd)) arms:
- Complete response (CR) rate, as defined by the International Myeloma Working Group (IMWG) criteria.
- Minimal residual disease (MRD) negativity rate in patients with CR.
- Very good partial response or better rate, as defined by the IMWG criteria.
- Overall survival (OS).
- To evaluate the overall response rate (ORR) as per IMWG criteria.
- To evaluate the time to progression (TTP) overall and by MRD status.
- To evaluate PFS by MRD status.
- To evaluate the duration of response (DOR) overall and by MRD status.
- To evaluate time to first response (TT1R).
- To evaluate time to best response (TTBR).
- To evaluate progression-free survival on next line of therapy (PFS2).
- To evaluate the sustained MRD negativity >12 months rate.
- To evaluate safety.
- To determine the pharmacokinetic (PK) profile of isatuximab in combination with bortezomib, lenalidomide, and dexamethasone (IVRd arm only).
- To evaluate the immunogenicity of isatuximab in patients receiving isatuximab (IVRd and crossover arms).
- To assess disease-specific and generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility, and health status.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Plasma Cell Myeloma | Drug: Isatuximab SAR650984 Drug: Bortezomib Drug: Lenalidomide Drug: Dexamethasone | Phase 3 |
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 : | Interventional (Clinical Trial) |
| Actual Enrollment : | 475 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 and Dexamethasone Versus Bortezomib, Lenalidomide and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Not Eligible for Transplant |
| Actual Study Start Date : | December 7, 2017 |
| Estimated Primary Completion Date : | April 5, 2026 |
| Estimated Study Completion Date : | June 30, 2027 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Multiple myeloma
MedlinePlus related topics:
Multiple Myeloma
| Arm | Intervention/treatment |
|---|---|
Experimental: Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm
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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: Subcutaneous Other Name: Velcade® Drug: Lenalidomide Pharmaceutical form: Capsules Route of administration: Oral Drug: Dexamethasone Pharmaceutical form: Tablets, ampoules or vials for injection Route of administration: Oral/Intravenous |
Active Comparator: Bortezomib/Lenalidomide/Dexamethasone = VRd arm
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Drug: Bortezomib
Pharmaceutical form: Lyophilized powder for injection Route of administration: Subcutaneous Other Name: Velcade® Drug: Lenalidomide Pharmaceutical form: Capsules Route of administration: Oral Drug: Dexamethasone Pharmaceutical form: Tablets, ampoules or vials for injection Route of administration: Oral/Intravenous |
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Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm
4-weeks cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone
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Drug: Isatuximab SAR650984
Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV) Other Name: Sarclisa Drug: Lenalidomide Pharmaceutical form: Capsules Route of administration: Oral Drug: Dexamethasone Pharmaceutical form: Tablets, ampoules or vials for injection Route of administration: Oral/Intravenous |
Primary Outcome Measures :
- Progression free survival (PFS) [ Time Frame: Up to approximately 100 months after the First Patient In (FPI) ]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 :
- Complete response rate (CR) [ Time Frame: Up to approximately 100 months after the FPI ]Defined as the proportion of patients with CR and stringent complete response (sCR) as assessed by the IRC using the IMWG criteria.
- Minimal residual disease (MRD) negativity rate for patients with CR [ Time Frame: Up to approximately 100 months after the FPI ]Proportion of patients with CR for whom MRD measurement is negative
- Very good partial response (VGPR) or better rate [ Time Frame: Up to approximately 100 months after the FPI ]Proportion of patients with sCR, CR and VGPR as assessed by the IRC using the International Myeloma Working Group (IMWG) criteria
- Overall survival (OS) [ Time Frame: Up to approximately 110 months after the FPI ]Defined as the time from the date of randomization to death from any cause
- Overall response rate (ORR) [ Time Frame: Up to approximately 100 months after the FPI 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 100 months after FPI ]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 100 months after the FPI ]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 100 months after the FPI ]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 100 months after the FPI ]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: Up to approximately 110 months after the FPI ]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 100 months after the FPI ]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
- Sustained MRD negativity ≥12 months rate [ Time Frame: Up to approximately 100 months after the FPI ]Defined as the proportion of patients with the maintenance of MRD negativity confirmed ≥12 months apart with no MRD positive test in between.
- 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)
- Immunogenicity [ Time Frame: Up to approximately 100 months after the FPI ]Presence of anti-drug antibodies against isatuximab
- Patient reported outcome (PRO): QLQ-C30 [ Time Frame: Up to approximately 100 months after the FPI ]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 100 months after the FPI ]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 100 months after the FPI ]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
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| Ages Eligible for Study: | 18 Years to 80 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
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.
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
Locations
Show 104 study locations
Sponsors and Collaborators
Sanofi
Investigators
| Study Director: | Clinical Sciences & Operations | Sanofi |
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT03319667 |
| Other Study ID Numbers: |
EFC12522 2017-002238-21 ( EudraCT Number ) U1111-1194-2121 ( Registry Identifier: ICTRP ) |
| First Posted: | October 24, 2017 Key Record Dates |
| Last Update Posted: | April 8, 2024 |
| Last Verified: | April 2024 |
| 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://vivli.org |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Sanofi:
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Anti-CD38 monoclonal antibody |
Additional relevant MeSH terms:
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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 |
Lenalidomide Bortezomib Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Immunologic Factors Angiogenesis Inhibitors |