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

• Register: EUCTR
• Last refreshed on: 8 August 2022
• Main ID: EUCTR2017-002238-21-LT
• Date of registration: 27/09/2017
• Prospective Registration: Yes
• Primary sponsor: Sanofi-aventis recherche & développement
• Public title: Clinical Benefit of SAR650984, Bortezomib, Lenalidomide and Dexamethasone Combination in NDMM Patients Not Eligible for Transplant
• Scientific 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 - Imroz
• Date of first enrolment: 25/10/2017
• Target sample size: 440
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002238-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, China, Czech Republic, Czechia, Denmark, France, Germany, Greece, Italy, Japan, Lithuania, Mexico, New Zealand, Poland, Portugal, Russian Federation, Spain, Sweden, Taiwan, Turkey, United States

Contacts

• Name: Clinical Study Unit
• Affiliation: Sanofi AB

• Name: Clinical Study Unit
• Affiliation: Sanofi AB

Key inclusion & exclusion criteria

Inclusion criteria:
-Multiple myeloma (International Myeloma Working Group [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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 220
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 220

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Plasma cell myeloma
MedDRA version: 21.1 Level: PT Classification code 10035226 Term: Plasma cell myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: isatuximab
Product Code: SAR650984
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Isatuximab
Current Sponsor code: SAR650984
Other descriptive name: SAR650984
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: VELCADE 3.5 mg powder for solution for injection
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: BORTEZOMIB
CAS Number: 179324-69-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3.5-

Trade Name: Dexamethasone 3.3 mg/mL solution for injection
Product Name: Dexamethasone
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Dexamethasone
Other descriptive name: DEXAMETHASONE BASE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 3.3-

Trade

Primary Outcome(s)

Secondary Objective: -To evaluate in both randomized 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,time to progression (TTP) overall and by MRD status,PFS by MRD status,duration of response (DOR) overall and by MRD status,time to first response (TT1R),time to best response (TTBR),progression-free survival on next line of therapy (PFS2),sustained MRD negativity >12 months rate,safety,PK profile of isatuximab in combination with bortezomib, lenalidomide, and dexamethasone (IVRd arm only),immunogenicity of isatuximab in patients receiving isatuximab (IVRd and crossover arms),disease-specific and generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility, and health status.

Primary end point(s): Progression free survival (PFS): 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

Timepoint(s) of evaluation of this end point: Up to approximately 100 months after the First Patient In (FPI)

Main 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 Outcome(s)

Secondary end point(s): 1. Complete response (CR): proportion of patients with CR and stringent complete response (sCR) as assessed by the IRC using the IMWG criteria
2. Minimal residual disease (MRD) negativity rate for patients with CR: proportion of patients with CR for whom MRD measurement is negative
3. Very good partial response (VGPR) or better rate: proportion of patients with sCR, CR and VGPR as assessed by the IRC using the International Myeloma Working Group (IMWG) criteria
4. Overall survival (OS): time from the date of randomization to death from any cause
5. Overall response rate (ORR): 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
6. Time to progression (TTP): time from randomization to date of first documentation of PD as assessed by the IRC using the IMWG criteria
7. Duration of response (DOR): 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
8. Time to first response (TT1R): time from randomization to the first IRC determined response (PR or better) that is subsequently confirmed
9. Time to best response (TTBR): time from randomization to the date of first occurrence of IRC determined best response (PR or better) that is
subsequently confirmed
10. PFS on next line of therapy (PFS2): 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
11. PFS in MRD negative patients: 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
12. Sustained MRD negativity =12 months rate: proportion of patients with the maintenance of MRD negativity confirmed =12 months apart
with no MRD positive test in between.
13. Adverse Events: 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
14. Assessment of PK parameter (Ctrough): pre-dose plasma isatuximab concentration
15. Immunogenicity: presence of anti-drug antibodies against Isatuximab
16. Patient reported outcome (PRO): QLQ-C30. Disease-specific HRQL will be assessed using the European Organization for Research and
Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ C30)
17. PRO: QLQ-MY20: disease- and treatment-related quality of life will be assessed using the EORTC myeloma module (QLQ MY20) questionnaire
18. PRO: EQ-5D-5L: 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)

Timepoint(s) of evaluation of this end point: 1, 2, 3, 6, 7, 8, 9, 11, 12, 15, 16, 17, 18. Up to approximately 100 months after the FPI
4. Up to approximately 110 months after the FPI
5. Up to approximately 100 months after the FPI assessment
10. At the cutoff for final OS analysis
13. Up to 30 days after end of treatment (EOT) visit
14. 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

Secondary ID(s)

EFC12522

2017-002238-21-CZ

Source(s) of Monetary Support

Sanofi-aventis recherche & développement

Ethics review

Status: Approved
Approval date: 20/10/2017
Contact: