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
- Conditions
- Plasma Cell Myeloma
- Interventions
- Registration Number
- NCT03319667
- Lead Sponsor
- Sanofi
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 475
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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm Isatuximab SAR650984 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 Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm Isatuximab SAR650984 4-weeks cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm Bortezomib 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 Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm Lenalidomide 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 Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd arm Dexamethasone 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 Bortezomib/Lenalidomide/Dexamethasone = VRd arm Bortezomib 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 Bortezomib/Lenalidomide/Dexamethasone = VRd arm Dexamethasone 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 Bortezomib/Lenalidomide/Dexamethasone = VRd arm Lenalidomide 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 Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm Lenalidomide 4-weeks cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone Isatuximab/Lenalidomide/Dexamethasone = IRd crossover arm Dexamethasone 4-weeks cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone
- Primary Outcome Measures
Name Time Method Progression free survival (PFS) Up to approximately 100 months after the First Participant 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
Name Time Method Complete response rate (CR) Up to approximately 100 months after the FPI Defined as the proportion of participants with CR and stringent complete response (sCR) as assessed by the IRC using the IMWG criteria.
Minimal residual disease (MRD) negativity rate for participants with CR Up to approximately 100 months after the FPI Proportion of participants with CR for whom MRD measurement is negative
Very good partial response (VGPR) or better rate Up to approximately 100 months after the FPI Proportion of participants with sCR, CR and VGPR as assessed by the IRC using the International Myeloma Working Group (IMWG) criteria
Overall survival (OS) 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) Up to approximately 100 months after the FPI assessment Proportion of participants 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) 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) 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 participants achieving sCR, CR, VGPR, or PR
Time to first response (TT1R) 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) 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) 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 participants 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 participants
Sustained MRD negativity ≥12 months rate Up to approximately 100 months after the FPI Defined as the proportion of participants with the maintenance of MRD negativity confirmed ≥12 months apart with no MRD positive test in between.
Adverse Events 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 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 Up to approximately 100 months after the FPI Presence of anti-drug antibodies against isatuximab
participants reported outcome (PRO): QLQ-C30 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 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 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)
Trial Locations
- Locations (104)
Investigational Site Number: 8400006
🇺🇸Fort Myers, Florida, United States
Investigational Site Number: 8400004
🇺🇸Saint Petersburg, Florida, United States
Investigational Site Number: 8400007
🇺🇸Kansas City, Missouri, United States
Investigational Site Number: 8400005
🇺🇸Nashville, Tennessee, United States
Investigational Site Number: 8400001
🇺🇸Houston, Texas, United States
Investigational Site Number : 0360003
🇦🇺Liverpool, New South Wales, Australia
Investigational Site Number : 0360001
🇦🇺Waratah, New South Wales, Australia
Investigational Site Number : 0360002
🇦🇺Wollongong, New South Wales, Australia
Investigational Site Number : 0360007
🇦🇺South Brisbane, Queensland, Australia
Investigational Site Number : 0360005
🇦🇺Clayton, Victoria, Australia
Investigational Site Number : 0360004
🇦🇺Heidelberg West, Victoria, Australia
Investigational Site Number : 0360006
🇦🇺Nedlands, Western Australia, Australia
Investigational Site Number : 0360008
🇦🇺West Perth, Western Australia, Australia
Investigational Site Number : 0560001
🇧🇪Liège, Belgium
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 : 1560009
🇨🇳Guangzhou, China
Investigational Site Number : 1560006
🇨🇳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, China
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, Czechia
Investigational Site Number : 2080002
🇩🇰Aalborg, Denmark
Investigational Site Number : 2080003
🇩🇰Aarhus N, Denmark
Investigational Site Number : 2080004
🇩🇰Odense C, Denmark
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, France
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, Germany
Investigational Site Number : 3000003
🇬🇷Athens, Greece
Investigational Site Number : 3000001
🇬🇷Athens, Greece
Investigational Site Number : 3000002
🇬🇷Thessaloniki, Greece
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, Italy
Investigational Site Number : 3920007
🇯🇵Nagoya-shi, Aichi, 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 : 3920009
🇯🇵Sendai-shi, Miyagi, Japan
Investigational Site Number : 3920005
🇯🇵Okayama-shi, Okayama, Japan
Investigational Site Number : 3920006
🇯🇵Sunto-gun, Shizuoka, Japan
Investigational Site Number : 3920001
🇯🇵Shibuya-ku, Tokyo, Japan
Investigational Site Number : 3920002
🇯🇵Shinjuku-ku, Tokyo, Japan
Investigational Site Number : 3920010
🇯🇵Yamagata-shi, Japan
Investigational Site Number : 4400002
🇱🇹Klaipeda, Lithuania
Investigational Site Number : 4400001
🇱🇹Vilnius, Lithuania
Investigational Site Number : 4840001
🇲🇽Monterrey, Nuevo León, Mexico
Investigational Site Number : 5540002
🇳🇿Takapuna, Auckland, New Zealand
Investigational Site Number : 5540003
🇳🇿Hamilton, Waikato, New Zealand
Investigational Site Number : 5540001
🇳🇿Auckland, New Zealand
Investigational Site Number : 6160003
🇵🇱Lodz, Lódzkie, Poland
Investigational Site Number : 6160001
🇵🇱Warszawa, Mazowieckie, Poland
Investigational Site Number : 6160002
🇵🇱Gdansk, Pomorskie, Poland
Investigational Site Number : 6160004
🇵🇱Poznan, Wielkopolskie, Poland
Investigational Site Number : 6200002
🇵🇹Braga, Portugal
Investigational Site Number : 6200006
🇵🇹Coimbra, Portugal
Investigational Site Number : 6200001
🇵🇹Lisboa, Portugal
Investigational Site Number : 6200005
🇵🇹Porto, Portugal
Investigational Site Number : 6200003
🇵🇹Porto, Portugal
Investigational Site Number : 6430001
🇷🇺Moscow, Russian Federation
Investigational Site Number : 6430002
🇷🇺Moscow, Russian Federation
Investigational Site Number : 7240005
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 7240004
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 7240003
🇪🇸Madrid, Spain
Investigational Site Number : 7240001
🇪🇸Murcia, Spain
Investigational Site Number : 7520002
🇸🇪Lund, Sweden
Investigational Site Number : 7520001
🇸🇪Stockholm, Sweden
Investigational Site Number : 1580003
🇨🇳Changhua, Taiwan
Investigational Site Number : 1580002
🇨🇳Taichung, Taiwan
Investigational Site Number : 1580001
🇨🇳Taipei, Taiwan
Investigational Site Number : 7920006
🇹🇷Adana, Turkey
Investigational Site Number : 7920007
🇹🇷Ankara, Turkey
Investigational Site Number : 7920001
🇹🇷Ankara, Turkey
Investigational Site Number : 7920002
🇹🇷Istanbul, Turkey
Investigational Site Number : 7920004
🇹🇷Izmir, Turkey
Investigational Site Number : 7920003
🇹🇷Izmir, Turkey
Investigational Site Number : 7920005
🇹🇷Kayseri, Turkey
Investigational Site Number : 7920008
🇹🇷Samsun, Turkey