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

Plasma Cell Myeloma Clinical Trial

— IMROZ  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03319667
• Other study ID #: EFC12522
• Secondary ID: 2017-002238-21U1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 7, 2017
• Est. completion date: June 30, 2027

Study information

• Verified date: April 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 475
• Est. completion date: June 30, 2027
• Est. primary completion date: April 5, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Plasma Cell Myeloma

Intervention

Drug:
• Isatuximab SAR650984
Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV)
• Bortezomib
Pharmaceutical form: Lyophilized powder for injection Route of administration: Subcutaneous
• Lenalidomide
Pharmaceutical form: Capsules Route of administration: Oral
• Dexamethasone
Pharmaceutical form: Tablets, ampoules or vials for injection Route of administration: Oral/Intravenous

Locations

Country	Name	City	State
Australia	Investigational Site Number :0360005	Clayton	Victoria
Australia	Investigational Site Number :0360004	Heidelberg West	Victoria
Australia	Investigational Site Number :0360003	Liverpool	New South Wales
Australia	Investigational Site Number :0360006	Nedlands	Western Australia
Australia	Investigational Site Number :0360007	South Brisbane	Queensland
Australia	Investigational Site Number :0360001	Waratah	New South Wales
Australia	Investigational Site Number :0360008	West Perth	Western Australia
Australia	Investigational Site Number :0360002	Wollongong	New South Wales
Belgium	Investigational Site Number :0560001	Liège
China	Investigational Site Number :1560002	Beijing
China	Investigational Site Number :1560003	Beijing
China	Investigational Site Number :1560008	Changchun
China	Investigational Site Number :1560007	Fuzhou
China	Investigational Site Number :1560006	Guangzhou
China	Investigational Site Number :1560009	Guangzhou
China	Investigational Site Number :1560005	Hangzhou
China	Investigational Site Number :1560014	Hangzhou
China	Investigational Site Number :1560004	Nanjing
China	Investigational Site Number :1560013	Shanghai
China	Investigational Site Number :1560011	Shenyang
China	Investigational Site Number :1560001	Tianjin
China	Investigational Site Number :1560012	Wuhan
Czechia	Investigational Site Number :2030002	Brno
Czechia	Investigational Site Number :2030007	Hradec Kralove
Czechia	Investigational Site Number :2030004	Olomouc
Czechia	Investigational Site Number :2030003	Ostrava - Poruba
Czechia	Investigational Site Number :2030006	Plzen
Czechia	Investigational Site Number :2030001	Praha 2
Denmark	Investigational Site Number :2080002	Aalborg
Denmark	Investigational Site Number :2080003	Aarhus N
Denmark	Investigational Site Number :2080004	Odense C
France	Investigational Site Number :2500011	Bayonne
France	Investigational Site Number :2500007	Caen
France	Investigational Site Number :2500009	Dijon
France	Investigational Site Number :2500008	La Roche Sur Yon
France	Investigational Site Number :2500001	Lille
France	Investigational Site Number :2500003	Nantes
France	Investigational Site Number :2500012	Paris
France	Investigational Site Number :2500002	Pessac
France	Investigational Site Number :2500006	Pierre Benite
France	Investigational Site Number :2500005	Poitiers Cedex
France	Investigational Site Number :2500004	TOULOUSE Cedex 9
France	Investigational Site Number :2500010	Vandoeuvre-les-nancy
Germany	Investigational Site Number :2760003	Berlin
Germany	Investigational Site Number :2760004	Frankfurt am Main
Germany	Investigational Site Number :2760001	Heidelberg
Germany	Investigational Site Number :2760005	Tübingen
Greece	Investigational Site Number :3000001	Athens
Greece	Investigational Site Number :3000003	Athens
Greece	Investigational Site Number :3000002	Thessaloniki
Italy	Investigational Site Number :3800005	Ancona
Italy	Investigational Site Number :3800003	Bergamo
Italy	Investigational Site Number :3800001	Bologna
Italy	Investigational Site Number :3800004	Brescia
Italy	Investigational Site Number :3800002	Torino
Japan	Investigational Site Number :3920004	Higashiibaraki-gun	Ibaraki
Japan	Investigational Site Number :3920008	Konan-ku, Yokohama-shi	Kanagawa
Japan	Investigational Site Number :3920003	Kumamoto-shi	Kumamoto
Japan	Investigational Site Number :3920007	Nagoya-shi	Aichi
Japan	Investigational Site Number :3920005	Okayama-shi	Okayama
Japan	Investigational Site Number :3920009	Sendai-shi	Miyagi
Japan	Investigational Site Number :3920001	Shibuya-ku	Tokyo
Japan	Investigational Site Number :3920002	Shinjuku-ku	Tokyo
Japan	Investigational Site Number :3920006	Sunto-gun	Shizuoka
Japan	Investigational Site Number :3920010	Yamagata-shi
Lithuania	Investigational Site Number :4400002	Klaipeda
Lithuania	Investigational Site Number :4400001	Vilnius
Mexico	Investigational Site Number :4840001	Monterrey	Nuevo León
New Zealand	Investigational Site Number :5540001	Auckland
New Zealand	Investigational Site Number :5540003	Hamilton	Waikato
New Zealand	Investigational Site Number :5540002	Takapuna	Auckland
Poland	Investigational Site Number :6160002	Gdansk	Pomorskie
Poland	Investigational Site Number :6160003	Lodz	Lódzkie
Poland	Investigational Site Number :6160004	Poznan	Wielkopolskie
Poland	Investigational Site Number :6160001	Warszawa	Mazowieckie
Portugal	Investigational Site Number :6200002	Braga
Portugal	Investigational Site Number :6200006	Coimbra
Portugal	Investigational Site Number :6200001	Lisboa
Portugal	Investigational Site Number :6200003	Porto
Portugal	Investigational Site Number :6200005	Porto
Russian Federation	Investigational Site Number :6430001	Moscow
Russian Federation	Investigational Site Number :6430002	Moscow
Spain	Investigational Site Number :7240004	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number :7240005	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number :7240003	Madrid
Spain	Investigational Site Number :7240001	Murcia
Sweden	Investigational Site Number :7520002	Lund
Sweden	Investigational Site Number :7520001	Stockholm
Taiwan	Investigational Site Number :1580003	Changhua
Taiwan	Investigational Site Number :1580002	Taichung
Taiwan	Investigational Site Number :1580001	Taipei
Turkey	Investigational Site Number :7920006	Adana
Turkey	Investigational Site Number :7920001	Ankara
Turkey	Investigational Site Number :7920007	Ankara
Turkey	Investigational Site Number :7920002	Istanbul
Turkey	Investigational Site Number :7920003	Izmir
Turkey	Investigational Site Number :7920004	Izmir
Turkey	Investigational Site Number :7920005	Kayseri
Turkey	Investigational Site Number :7920008	Samsun
United States	Investigational Site Number :8400006	Fort Myers	Florida
United States	Investigational Site Number :8400001	Houston	Texas
United States	Investigational Site Number :8400007	Kansas City	Missouri
United States	Investigational Site Number :8400005	Nashville	Tennessee
United States	Investigational Site Number :8400004	Saint Petersburg	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival (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.	Up to approximately 100 months after the First Patient In (FPI)
Secondary	Complete response rate (CR)	Defined as the proportion of patients with CR and stringent complete response (sCR) as assessed by the IRC using the IMWG criteria.	Up to approximately 100 months after the FPI
Secondary	Minimal residual disease (MRD) negativity rate for patients with CR	Proportion of patients with CR for whom MRD measurement is negative	Up to approximately 100 months after the FPI
Secondary	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	Up to approximately 100 months after the FPI
Secondary	Overall survival (OS)	Defined as the time from the date of randomization to death from any cause	Up to approximately 110 months after the FPI
Secondary	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	Up to approximately 100 months after the FPI assessment
Secondary	Time to progression (TTP)	Defined as the time from randomization to date of first documentation of PD as assessed by the IRC using the IMWG criteria	Up to approximately 100 months after FPI
Secondary	Duration of response (DOR)	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	Up to approximately 100 months after the FPI
Secondary	Time to first response (TT1R)	Time from randomization to the first IRC determined response (PR or better) that is subsequently confirmed	Up to approximately 100 months after the FPI
Secondary	Time to best response (TTBR)	Defined as the time from randomization to the date of first occurrence of IRC determined best response (PR or better) that is subsequently confirmed	Up to approximately 100 months after the FPI
Secondary	PFS on next line of therapy (PFS2)	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	Up to approximately 110 months after the FPI
Secondary	PFS in MRD negative patients	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	Up to approximately 100 months after the FPI
Secondary	Sustained MRD negativity =12 months rate	Defined as the proportion of patients with the maintenance of MRD negativity confirmed =12 months apart with no MRD positive test in between.	Up to approximately 100 months after the FPI
Secondary	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	Up to 30 days after end of treatment (EOT) visit
Secondary	Assessment of PK parameter: Ctrough	Isatuximab: Pre-dose plasma isatuximab concentration (Ctrough)	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	Immunogenicity	Presence of anti-drug antibodies against isatuximab	Up to approximately 100 months after the FPI
Secondary	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)	Up to approximately 100 months after the FPI
Secondary	PRO: QLQ-MY20	Disease- and treatment-related quality of life will be assessed using the EORTC myeloma module (QLQ-MY20) questionnaire	Up to approximately 100 months after the FPI
Secondary	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)	Up to approximately 100 months after the FPI