Clinical trial NCT03319667: A Study to Investigate the Clinical Benefit of Isatuximab in Combination With Bortezomib, Lenalidomide and Dexamethasone in Adults With Newly Diagnosed Multiple Myeloma Not Eligible for Transplant
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Plasma Cell Myeloma
Keywords: Anti-CD38 monoclonal antibody
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2017-10-24
Enrollment: 475
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel and crossover
Primary purpose: TREATMENT

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 participants 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 participants 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 participants 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.

Detailed description: The duration of the study for each participant 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.

Eligibility criteria: Inclusion Criteria:

Inclusion criteria :

* Multiple myeloma (IMWG criteria).
* Newly diagnosed multiple myeloma not eligible for transplant due to age (≥ 65 years) or participants \< 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.

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: Up to approximately 100 months after the First Participant In (FPI)
Secondary outcomes:
measure: Complete response rate (CR)
timeFrame: Up to approximately 100 months after the FPI
measure: Minimal residual disease (MRD) negativity rate for participants with CR
timeFrame: Up to approximately 100 months after the FPI
measure: Very good partial response (VGPR) or better rate
timeFrame: Up to approximately 100 months after the FPI
measure: Overall survival (OS)
timeFrame: Up to approximately 110 months after the FPI
measure: Overall response rate (ORR)
timeFrame: Up to approximately 100 months after the FPI assessment
measure: Time to progression (TTP)
timeFrame: Up to approximately 100 months after FPI
measure: Duration of response (DOR)
timeFrame: Up to approximately 100 months after the FPI
measure: Time to first response (TT1R)
timeFrame: Up to approximately 100 months after the FPI
measure: Time to best response (TTBR)
timeFrame: Up to approximately 100 months after the FPI
measure: PFS on next line of therapy (PFS2)
timeFrame: Up to approximately 110 months after the FPI
measure: PFS in MRD negative participants
timeFrame: Up to approximately 100 months after the FPI
measure: Sustained MRD negativity ≥12 months rate
timeFrame: Up to approximately 100 months after the FPI
measure: Adverse Events
timeFrame: Up to 30 days after end of treatment (EOT) visit
measure: Assessment of PK parameter: Ctrough
timeFrame: 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)
measure: Immunogenicity
timeFrame: Up to approximately 100 months after the FPI
measure: participants reported outcome (PRO): QLQ-C30
timeFrame: Up to approximately 100 months after the FPI
measure: PRO: QLQ-MY20
timeFrame: Up to approximately 100 months after the FPI
measure: PRO: EQ-5D-5L
timeFrame: Up to approximately 100 months after the FPI
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Investigational Site Number: 8400006
state: Florida
city: Saint Petersburg
country: United States
facility: Investigational Site Number: 8400004
state: Florida
city: Kansas City
country: United States
facility: Investigational Site Number: 8400007
state: Missouri
city: Nashville
country: United States
facility: Investigational Site Number: 8400005
state: Tennessee
city: Houston
country: United States
facility: Investigational Site Number: 8400001
state: Texas
city: Liverpool
country: Australia
facility: Investigational Site Number : 0360003
state: New South Wales
city: Waratah
country: Australia
facility: Investigational Site Number : 0360001
state: New South Wales
city: Wollongong
country: Australia
facility: Investigational Site Number : 0360002
state: New South Wales
city: South Brisbane
country: Australia
facility: Investigational Site Number : 0360007
state: Queensland
city: Clayton
country: Australia
facility: Investigational Site Number : 0360005
state: Victoria
city: Heidelberg West
country: Australia
facility: Investigational Site Number : 0360004
state: Victoria
city: Nedlands
country: Australia
facility: Investigational Site Number : 0360006
state: Western Australia
city: West Perth
country: Australia
facility: Investigational Site Number : 0360008
state: Western Australia
city: Liège
country: Belgium
facility: Investigational Site Number : 0560001
city: Beijing
country: China
facility: Investigational Site Number : 1560002
city: Beijing
country: China
facility: Investigational Site Number : 1560003
city: Changchun
country: China
facility: Investigational Site Number : 1560008
city: Fuzhou
country: China
facility: Investigational Site Number : 1560007
city: Guangzhou
country: China
facility: Investigational Site Number : 1560009
city: Guangzhou
country: China
facility: Investigational Site Number : 1560006
city: Hangzhou
country: China
facility: Investigational Site Number : 1560005
city: Hangzhou
country: China
facility: Investigational Site Number : 1560014
city: Nanjing
country: China
facility: Investigational Site Number : 1560004
city: Shanghai
country: China
facility: Investigational Site Number : 1560013
city: Shenyang
country: China
facility: Investigational Site Number : 1560011
city: Tianjin
country: China
facility: Investigational Site Number : 1560001
city: Wuhan
country: China
facility: Investigational Site Number : 1560012
city: Brno
country: Czechia
facility: Investigational Site Number : 2030002
city: Hradec Kralove
country: Czechia
facility: Investigational Site Number : 2030007
city: Olomouc
country: Czechia
facility: Investigational Site Number : 2030004
city: Ostrava - Poruba
country: Czechia
facility: Investigational Site Number : 2030003
city: Plzen
country: Czechia
facility: Investigational Site Number : 2030006
city: Praha 2
country: Czechia
facility: Investigational Site Number : 2030001
city: Aalborg
country: Denmark
facility: Investigational Site Number : 2080002
city: Aarhus N
country: Denmark
facility: Investigational Site Number : 2080003
city: Odense C
country: Denmark
facility: Investigational Site Number : 2080004
city: Bayonne
country: France
facility: Investigational Site Number : 2500011
city: Caen
country: France
facility: Investigational Site Number : 2500007
city: Dijon
country: France
facility: Investigational Site Number : 2500009
city: La Roche Sur Yon
country: France
facility: Investigational Site Number : 2500008
city: Lille
country: France
facility: Investigational Site Number : 2500001
city: Nantes
country: France
facility: Investigational Site Number : 2500003
city: Paris
country: France
facility: Investigational Site Number : 2500012
city: Pessac
country: France
facility: Investigational Site Number : 2500002
city: Pierre Benite
country: France
facility: Investigational Site Number : 2500006
city: Poitiers Cedex
country: France
facility: Investigational Site Number : 2500005
city: TOULOUSE Cedex 9
country: France
facility: Investigational Site Number : 2500004
city: Vandoeuvre-les-nancy
country: France
facility: Investigational Site Number : 2500010
city: Berlin
country: Germany
facility: Investigational Site Number : 2760003
city: Frankfurt am Main
country: Germany
facility: Investigational Site Number : 2760004
city: Heidelberg
country: Germany
facility: Investigational Site Number : 2760001
city: Tübingen
country: Germany
facility: Investigational Site Number : 2760005
city: Athens
country: Greece
facility: Investigational Site Number : 3000003
city: Athens
country: Greece
facility: Investigational Site Number : 3000001
city: Thessaloniki
country: Greece
facility: Investigational Site Number : 3000002
city: Ancona
country: Italy
facility: Investigational Site Number : 3800005
city: Bergamo
country: Italy
facility: Investigational Site Number : 3800003
city: Bologna
country: Italy
facility: Investigational Site Number : 3800001
city: Brescia
country: Italy
facility: Investigational Site Number : 3800004
city: Torino
country: Italy
facility: Investigational Site Number : 3800002
city: Nagoya-shi
country: Japan
facility: Investigational Site Number : 3920007
state: Aichi
city: Higashiibaraki-gun
country: Japan
facility: Investigational Site Number : 3920004
state: Ibaraki
city: Konan-ku, Yokohama-shi
country: Japan
facility: Investigational Site Number : 3920008
state: Kanagawa
city: Kumamoto-shi
country: Japan
facility: Investigational Site Number : 3920003
state: Kumamoto
city: Sendai-shi
country: Japan
facility: Investigational Site Number : 3920009
state: Miyagi
city: Okayama-shi
country: Japan
facility: Investigational Site Number : 3920005
state: Okayama
city: Sunto-gun
country: Japan
facility: Investigational Site Number : 3920006
state: Shizuoka
city: Shibuya-ku
country: Japan
facility: Investigational Site Number : 3920001
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Investigational Site Number : 3920002
state: Tokyo
city: Yamagata-shi
country: Japan
facility: Investigational Site Number : 3920010
city: Klaipeda
country: Lithuania
facility: Investigational Site Number : 4400002
city: Vilnius
country: Lithuania
facility: Investigational Site Number : 4400001
city: Monterrey
country: Mexico
facility: Investigational Site Number : 4840001
state: Nuevo León
city: Takapuna
country: New Zealand
facility: Investigational Site Number : 5540002
state: Auckland
city: Hamilton
country: New Zealand
facility: Investigational Site Number : 5540003
state: Waikato
city: Auckland
country: New Zealand
facility: Investigational Site Number : 5540001
city: Lodz
country: Poland
facility: Investigational Site Number : 6160003
state: Lódzkie
city: Warszawa
country: Poland
facility: Investigational Site Number : 6160001
state: Mazowieckie
city: Gdansk
country: Poland
facility: Investigational Site Number : 6160002
state: Pomorskie
city: Poznan
country: Poland
facility: Investigational Site Number : 6160004
state: Wielkopolskie
city: Braga
country: Portugal
facility: Investigational Site Number : 6200002
city: Coimbra
country: Portugal
facility: Investigational Site Number : 6200006
city: Lisboa
country: Portugal
facility: Investigational Site Number : 6200001
city: Porto
country: Portugal
facility: Investigational Site Number : 6200005
city: Porto
country: Portugal
facility: Investigational Site Number : 6200003
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430001
city: Moscow
country: Russian Federation
facility: Investigational Site Number : 6430002
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240005
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240004
state: Barcelona [Barcelona]
city: Madrid
country: Spain
facility: Investigational Site Number : 7240003
city: Murcia
country: Spain
facility: Investigational Site Number : 7240001
city: Lund
country: Sweden
facility: Investigational Site Number : 7520002
city: Stockholm
country: Sweden
facility: Investigational Site Number : 7520001
city: Changhua
country: Taiwan
facility: Investigational Site Number : 1580003
city: Taichung
country: Taiwan
facility: Investigational Site Number : 1580002
city: Taipei
country: Taiwan
facility: Investigational Site Number : 1580001
city: Adana
country: Turkey
facility: Investigational Site Number : 7920006
city: Ankara
country: Turkey
facility: Investigational Site Number : 7920007
city: Ankara
country: Turkey
facility: Investigational Site Number : 7920001
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920002
city: Izmir
country: Turkey
facility: Investigational Site Number : 7920004
city: Izmir
country: Turkey
facility: Investigational Site Number : 7920003
city: Kayseri
country: Turkey
facility: Investigational Site Number : 7920005
city: Samsun
country: Turkey
facility: Investigational Site Number : 7920008
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: