Clinical trial NCT03275285: Multinational Clinical Study Comparing Isatuximab, Carfilzomib And Dexamethasone To Carfilzomib And Dexamethasone In Relapse And/Or Refractory Multiple Myeloma Patients
Official title: Randomized, Open Label, Multicenter Study Assessing The Clinical Benefit Of Isatuximab Combined With Carfilzomib (Kyprolis®) And Dexamethasone Versus Carfilzomib With Dexamethasone In Patients With Relapse And/Or Refractory Multiple Myeloma Previously Treated With 1 to 3 Prior Lines
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Plasma Cell Myeloma
Keywords: Anti-CD38 monoclonal antibody
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2017-09-07
Enrollment: 302
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study it to compare the efficacity of isatuximab when combined to carfilzomib and dexamethasone versus carfilzomib and dexamethasone in patients with multiple myeloma already treated with 1 to 3 prior lines of therapy.

Detailed description: The duration of the study for a patient will include a period for screening of up to 3 weeks. Patients will be treated until disease progression, unacceptable AE, or patient decision to stop the study treatment. After study treatment discontinuation, patients will have follow-up visits until the analysis of overall survival.

Eligibility criteria: Inclusion criteria:

* Participants with MM previously treated with prior 1 to 3 lines and with measurable serum M-protein (\>= 0.5 gram/deciliter) and/or urine M-protein (\>= 200 milligram/24 hours).

Exclusion criteria:

* Participants previously pretreated with carfilzomib, who never achieved at least one minor response during previous therapies and/or last previous therapy completed within 14 last days.
* Participants with serum free light chain (FLC) measurable disease only.
* Participants less than 18 years old, participants with Eastern Cooperative Oncology Group performance status more than 2.
* Participants with inadequate biological tests.
* Participants with myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association class III or IV congestive heart failure, superior or equal to grade 3 arrhythmias, stroke or transient ischemic attack within last 6 months, and/or left ventricular ejection fraction lower than 40%.
* Participants with previous cancer unless disease free for more than 5 years or in situ cancer curatively treated.
* Participants with known acquired immunodeficiency syndrome related illness or human immunodeficiency virus requiring antiretroviral treatment, or hepatitis A, B, or C active infection.
* Women of childbearing potential or male participant with women of childbearing potential who do not agree to use highly effective method of birth control.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Progression Free Survival (PFS) As Determined by Independent Response Committee (IRC): Primary Analysis
timeFrame: From randomization until the primary analysis data cut-off date of 7 Feb 2020 (median duration of follow-up was 20.73 months)
measure: Progression Free Survival as Determined by Independent Response Committee: [Event Censored if Occurred >8 Weeks From Last Disease Assessment]: Primary Analysis
timeFrame: From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)
measure: Progression Free Survival as Determined by Independent Response Committee: Final Analysis
timeFrame: From randomization until the final analysis data cut-off date of 14 January 2022 (the median duration of follow-up was 43.96 months)
measure: Progression Free Survival as Determined by Independent Response Committee [Event Censored if Occurred >8 Weeks From Last Disease Assessment]: Final Analysis
timeFrame: From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)
Secondary outcomes:
measure: Percentage of Participants With Overall Response (OR) as Determined by Independent Response Committee: Primary Analysis
timeFrame: From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)
measure: Percentage of Participants With Very Good Partial Response (VGPR) or Better as Determined by Independent Response Committee: Primary Analysis
timeFrame: From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)
measure: Percentage of Participants With VGPR or Better With Minimal Residual Disease (MRD) Negativity: Primary Analysis
timeFrame: From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)
measure: Percentage of Participants With VGPR or Better With Minimal Residual Disease (MRD) Negativity: Final Analysis
timeFrame: From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)
measure: Percentage of Participants With Complete Response (CR) as Per Independent Response Committee: Final Analysis
timeFrame: From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)
measure: Percentage of Participants With Complete Response With MRD Negativity: Final Analysis
timeFrame: From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)
measure: Overall Survival (OS)
timeFrame: From randomization until the final analysis data cut-off date of 7 Feb 2023 (the median duration of follow-up was 56.61 months)
measure: Duration of Response (DOR): Primary Analysis
timeFrame: From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)
measure: Time to Progression (TTP): Primary Analysis
timeFrame: From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)
measure: Time to First Response: Primary Analysis
timeFrame: From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)
measure: Time to Best Response: Primary Analysis
timeFrame: From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)
measure: Second Progression Free Survival (PFS2): Final Analysis - Data Cut-off Date of 14 Jan 2022
timeFrame: From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)
measure: Second Progression Free Survival (PFS2): Overal Survival Analysis - Data Cut-off Date of 07 Feb 2023
timeFrame: From randomization until the overal survival analysis data cut-off date of 07 Feb 2023 (the median duration of follow-up was 56.61 months)
measure: Number of Participants With Renal Response (RR): Primary Analysis
timeFrame: From the first dose of study treatment to 30 days following the last administration of study treatment (maximum duration: up to 114 weeks)
measure: Health Related Quality of Life (HRQL): Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 30 Items (EORTC QLQ-C30): Global Health Status Score at Specified Timepoints
timeFrame: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)
measure: HRQL: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 20 Items (EORTC QLQ-MY20): Disease Symptoms Domain Score at Specified Timepoints: Primary Analysis
timeFrame: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)
measure: HRQL: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 20 Items (EORTC QLQ-MY20): Side Effects of Treatment at Specified Timepoints: Primary Analysis
timeFrame: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)
measure: HRQL: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 20 Items (EORTC QLQ-MY20): Body Image Score at Specified Timepoints: Primary Analysis
timeFrame: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)
measure: HRQL: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 20 Items (EORTC QLQ-MY20): Future Perspective at Specified Timepoints: Primary Analysis
timeFrame: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)
measure: HRQL: Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints: Primary Analysis
timeFrame: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)
measure: HRQL: Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) at Specified Timepoints: Primary Analysis
timeFrame: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)
measure: Pharmacokinetics: Plasma Concentration at End of Infusion (Ceoi) of Isatuximab: Primary Analysis
timeFrame: End of infusion on Cycle 1 Day 1 and Cycle 1 Day 15; Cycle 2 Day 1
measure: Pharmacokinetics: Plasma Concentration of Isatuximab at Ctrough: Primary Analysis
timeFrame: Pre-infusion on Cycle 1 Day 1, Day 8, Day 15 and Day 22, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1, Cycle 8 Day 1, Cycle 9 Day 1 and Cycle 10 Day 1
measure: Pharmacokinetics: Maximum Observed Concentration (Cmax) of Carfilzomib: Primary Analysis
timeFrame: Cycle 1: pre-dose (0 hour), 30 minutes (min), 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
measure: Pharmacokinetics: Clast of Carfilzomib: Primary Analysis
timeFrame: Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
measure: Pharmacokinetics: Tmax of Carfilzomib: Primary Analysis
timeFrame: Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
measure: Pharmacokinetics: Tlast of Carfilzomib: Primary Analysis
timeFrame: Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
measure: Pharmacokinetics: Area Under the Plasma Concentration Time Curve (AUC) of Carfilzomib: Primary Analysis
timeFrame: Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
measure: Pharmacokinetics: Area Under the Plasma Concentration Time Curve From Time 0 to Last Quantifiable Concentration (AUClast) of Carfilzomib: Primary Analysis
timeFrame: Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
measure: Pharmacokinetics: Percentage of Extrapolation of AUC (AUCext) of Carfilzomib: Primary Analysis
timeFrame: Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
measure: Pharmacokinetics: Terminal Half-life (t1/2z) of Carfilzomib: Primary Analysis
timeFrame: Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
measure: Pharmacokinetics: Clearance at Steady State (CLss) of Carfilzomib: Primary Analysis
timeFrame: Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
measure: Pharmacokinetics: Volume of Distribution at Steady State (Vss) of Carfilzomib: Primary Analysis
timeFrame: Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15
measure: Number of Participants With Anti-Drug Antibodies (ADA): Primary Analysis
timeFrame: From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: 111 weeks)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs): Final Analysis
timeFrame: From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: up to 265 weeks for Kd arm and 268 weeks for IKd arm)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF MS Center Site Number : 8400002
state: California
city: Spartanburg
country: United States
facility: Spartanburg Medical Center Site Number : 8400003
state: South Carolina
city: Blacktown
country: Australia
facility: Investigational Site Number : 0360005
state: New South Wales
city: Tweed Heads
country: Australia
facility: Investigational Site Number : 0360006
state: New South Wales
city: Wollongong
country: Australia
facility: Investigational Site Number : 0360002
state: New South Wales
city: Fitzroy
country: Australia
facility: Investigational Site Number : 0360001
state: Victoria
city: Heidelberg West
country: Australia
facility: Investigational Site Number : 0360004
state: Victoria
city: Nedlands
country: Australia
facility: Investigational Site Number : 0360007
state: Western Australia
city: West Perth
country: Australia
facility: Investigational Site Number : 0360008
state: Western Australia
city: Salvador
country: Brazil
facility: Hospital Sao Rafael - Rede D'OR Sao Luiz Site Number : 0760005
state: Bahia
city: Porto Alegre
country: Brazil
facility: Hospital Mae de Deus Site Number : 0760003
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Hospital de Amor - Hospital do Cancer de Barretos - Fundacao Pio XII Site Number : 0760001
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas de Sao Paulo Site Number : 0760002
state: São Paulo
city: Rio De Janeiro
country: Brazil
facility: Instituto COI de Educacao e Pesquisa Site Number : 0760004
city: Surrey
country: Canada
facility: Investigational Site Number : 1240003
state: British Columbia
city: Saint John
country: Canada
facility: Investigational Site Number : 1240001
state: New Brunswick
city: Montreal
country: Canada
facility: Investigational Site Number : 1240002
state: Quebec
city: Brno
country: Czechia
facility: Investigational Site Number : 2030002
city: Olomouc
country: Czechia
facility: Investigational Site Number : 2030004
city: Ostrava - Poruba
country: Czechia
facility: Investigational Site Number : 2030003
city: Praha 2
country: Czechia
facility: Investigational Site Number : 2030001
city: Lille
country: France
facility: Investigational Site Number : 2500003
city: Nantes
country: France
facility: Investigational Site Number : 2500001
city: Paris
country: France
facility: Investigational Site Number : 2500006
city: Pessac
country: France
facility: Investigational Site Number : 2500002
city: Pierre Benite
country: France
facility: Investigational Site Number : 2500005
city: POITIERS Cedex
country: France
facility: Investigational Site Number : 2500004
city: Athens
country: Greece
facility: Investigational Site Number : 3000002
city: Athens
country: Greece
facility: Investigational Site Number : 3000005
city: Athens
country: Greece
facility: Investigational Site Number : 3000001
city: Patra
country: Greece
facility: Investigational Site Number : 3000004
city: Thessaloniki
country: Greece
facility: Investigational Site Number : 3000003
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480003
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480001
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480004
city: Kaposvár
country: Hungary
facility: Investigational Site Number : 3480005
city: Bologna
country: Italy
facility: Investigational Site Number : 3800003
city: Pisa
country: Italy
facility: Investigational Site Number : 3800001
city: Reggio Emilia
country: Italy
facility: Investigational Site Number : 3800004
city: Torino
country: Italy
facility: Investigational Site Number : 3800002
city: Shiwa-gun
country: Japan
facility: Investigational Site Number : 3920005
state: Iwate
city: Kumamoto-shi
country: Japan
facility: Investigational Site Number : 3920007
state: Kumamoto
city: Suwa-shi
country: Japan
facility: Investigational Site Number : 3920001
state: Nagano
city: Sunto-gun
country: Japan
facility: Investigational Site Number : 3920003
state: Shizuoka
city: Shibuya-ku
country: Japan
facility: Investigational Site Number : 3920004
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Investigational Site Number : 3920006
state: Tokyo
city: Yamagata-shi
country: Japan
facility: Investigational Site Number : 3920002
city: Busan
country: Korea, Republic of
facility: Investigational Site Number : 4100006
state: Busan-gwangyeoksi
city: Gangnam-gu
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100004
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100005
city: Auckland
country: New Zealand
facility: Investigational Site Number : 5540001
city: Wellington
country: New Zealand
facility: Investigational Site Number : 5540002
city: Ekaterinburg
country: Russian Federation
facility: Investigational Site Number : 6430002
city: Kirov
country: Russian Federation
facility: Investigational Site Number : 6430003
city: Novosibirsk
country: Russian Federation
facility: Investigational Site Number : 6430004
city: Badalona
country: Spain
facility: Investigational Site Number : 7240001
state: Catalunya [Cataluña]
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240005
state: Catalunya [Cataluña]
city: Valencia
country: Spain
facility: Investigational Site Number : 7240002
state: Valenciana, Comunidad
city: Madrid
country: Spain
facility: Investigational Site Number : 7240003
city: Sevilla
country: Spain
facility: Investigational Site Number : 7240004
city: Adana
country: Turkey
facility: Investigational Site Number : 7920003
city: Ankara
country: Turkey
facility: Investigational Site Number : 7920001
city: Bursa
country: Turkey
facility: Investigational Site Number : 7920005
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920002
city: Samsun
country: Turkey
facility: Investigational Site Number : 7920004
city: Plymouth
country: United Kingdom
facility: Investigational Site Number : 8260004
state: Devon
city: Leicester
country: United Kingdom
facility: Investigational Site Number : 8260005
state: Leicestershire
city: Bristol
country: United Kingdom
facility: Investigational Site Number : 8260001
state: Somerset
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Moreau P, Dimopoulos MA, Mikhael J, Yong K, Capra M, Facon T, Hajek R, Spicka I, Baker R, Kim K, Martinez G, Min CK, Pour L, Leleu X, Oriol A, Koh Y, Suzuki K, Risse ML, Asset G, Mace S, Martin T; IKEMA study group. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet. 2021 Jun 19;397(10292):2361-2371. doi: 10.1016/S0140-6736(21)00592-4. Epub 2021 Jun 4.
citation: Martin TG, Capra M, Mohty M, Suzuki K, Quach H, Cavo M, Moreau P, Dimopoulos M, Yong K, Tekle C, Foster MC, Barnes Y, Risse ML, Mikhael J. Isatuximab Plus Carfilzomib and Dexamethasone Versus Carfilzomib and Dexamethasone in Patients with Relapsed Multiple Myeloma: IKEMA Subgroup Analysis by Prior Transplantation. Transplant Cell Ther. 2023 Feb;29(2):134.e1-134.e7. doi: 10.1016/j.jtct.2022.11.005. Epub 2022 Nov 11.
citation: Chami B, Okuda M, Moayeri M, Pirenne F, Hidaka Y, Nambiar A, Song Z, Bedel O, Zhang B, Hopke J, Deng G, Zhu C, Mace S, Chiron M, Adrian F, Fukao T, Basile FG, Martin T. Anti-CD38 monoclonal antibody interference with blood compatibility testing: Differentiating isatuximab and daratumumab via functional epitope mapping. Transfusion. 2022 Nov;62(11):2334-2348. doi: 10.1111/trf.17137. Epub 2022 Oct 14.
citation: Moreau P, Dimopoulos MA, Yong K, Mikhael J, Risse ML, Asset G, Martin T. Isatuximab plus carfilzomib/dexamethasone versus carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma: IKEMA Phase III study design. Future Oncol. 2020 Jan;16(2):4347-4358. doi: 10.2217/fon-2019-0431. Epub 2019 Dec 13.