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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02990338




Registration number
NCT02990338
Ethics application status
Date submitted
4/12/2016
Date registered
13/12/2016

Titles & IDs
Public title
Multinational Clinical Study Comparing Isatuximab, Pomalidomide, and Dexamethasone to Pomalidomide and Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma Patients
Scientific title
A Phase 3 Randomized, Open-label, Multicenter Study Comparing Isatuximab (SAR650984) in Combination With Pomalidomide and Low-Dose Dexamethasone Versus Pomalidomide and Low-Dose Dexamethasone in Patients With Refractory or Relapsed and Refractory Multiple Myeloma
Secondary ID [1] 0 0
U1111-1180-6262
Secondary ID [2] 0 0
EFC14335
Universal Trial Number (UTN)
Trial acronym
ICARIA-MM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Plasma Cell Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Isatuximab
Treatment: Drugs - Pomalidomide
Treatment: Drugs - Dexamethasone

Active comparator: Pd (pomalidomide + dexamethasone) - Participants received pomalidomide 4 milligrams (mg) Per os (PO) on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants greater than or equal to (\>=) 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 241.6 weeks).

Experimental: IPd (isatuximab + pomalidomide + dexamethasone) - Participants received isatuximab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 245.6 weeks).


Treatment: Drugs: Isatuximab
Pharmaceutical form: solution for infusion Route of administration: intravenous

Treatment: Drugs: Pomalidomide
Pharmaceutical form: capsule Route of administration: oral

Treatment: Drugs: Dexamethasone
Pharmaceutical form: tablets or solution for infusion Route of administration: oral or intravenous
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
From the date of randomization to the date of first documentation of progression, or the date of death from any cause, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration: 76.7 weeks)
Secondary outcome [1] 0 0
Overall Response Rate (ORR): Percentage of Participants With Disease Response as Per Independent Response Committee (IRC)
Timepoint [1] 0 0
From the date of randomization to the date of first documentation of progression or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)
Secondary outcome [2] 0 0
Percentage of Participants With Best Overall Response (BOR) as Per Independent Response Committee
Timepoint [2] 0 0
From the date of randomization until disease progression, or death, initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)
Secondary outcome [3] 0 0
Percentage of Participants With Very Good Partial Response (VGPR) or Better as Per Independent Response Committee
Timepoint [3] 0 0
From the date of randomization to the date of first documentation of progression, death, initiation of further anti-myeloma treatment, or data cut-off whichever comes first (maximum duration 76.7 weeks)
Secondary outcome [4] 0 0
Clinical Benefit Rate (CBR): Percentage of Participants With Clinical Benefit as Per Independent Response Committee
Timepoint [4] 0 0
From the date of randomization to the date of first documentation of progression, death, initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)
Secondary outcome [5] 0 0
Overall Survival (OS): Final Analysis
Timepoint [5] 0 0
From the date of randomization to date of death from any cause or data cut-off date, whichever was earlier (maximum duration 245.6 weeks)
Secondary outcome [6] 0 0
Time to Progression (TTP) as Per Independent Response Committee
Timepoint [6] 0 0
From the date of randomization to the date of first documentation of progression, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)
Secondary outcome [7] 0 0
Progression Free Survival in High Risk Cytogenetic Population
Timepoint [7] 0 0
From the date of randomization to the date of first documentation of progression, or the date of death from any cause, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)
Secondary outcome [8] 0 0
Duration of Response (DOR) as Per Independent Response Committee
Timepoint [8] 0 0
From the date of the first IRC determined response to the date of first IRC progression or death, whichever occurred first (maximum duration 76.7 weeks)
Secondary outcome [9] 0 0
Time to First Response (TT1R) as Per Independent Response Committee
Timepoint [9] 0 0
From the date of randomization to the date of first IRC determined response, or death or data cut-off whichever comes first (maximum duration 76.7 weeks)
Secondary outcome [10] 0 0
Time to Best Response (TTBR) as Per Independent Response Committee
Timepoint [10] 0 0
From the date of randomization to date of first occurrence of IRC determined best overall response or data cut-off whichever comes first (maximum duration 76.7 weeks)
Secondary outcome [11] 0 0
Number of Participants With Minimal Residual Disease (MRD)
Timepoint [11] 0 0
Up to 76.7 weeks
Secondary outcome [12] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Timepoint [12] 0 0
From randomization up to 30 days after last dose of study drug (maximum duration up to 241.6 weeks for Pd arm and 245.6 weeks for IPd arm)
Secondary outcome [13] 0 0
Pharmacokinetics (PK) Parameter: Plasma Concentration of Isatuximab at End of Infusion (CEOI)
Timepoint [13] 0 0
End of infusion on Cycle(C)1 Day(D)1 and Cycle1 Day 15; Cycle 2 Day 1; and Cycle 4 Day 1
Secondary outcome [14] 0 0
Pharmacokinetic Parameter: Accumulation Ratio of Isatuximab at Concentration at the End of Infusion (CEOI)
Timepoint [14] 0 0
End of infusion on Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 4 Day 1
Secondary outcome [15] 0 0
Pharmacokinetic Parameter: Plasma Concentration of Isatuximab at 1 Hour After End of Infusion (CEOI+1 Hour)
Timepoint [15] 0 0
Cycle 1:1 hour after End of Infusion on Day 1; Cycle 4:1 hour after End of Infusion on Day 1
Secondary outcome [16] 0 0
PK Parameter: Plasma Concentration of Isatuximab at Ctrough
Timepoint [16] 0 0
Pre-infusion on C1D1, C1D8, C1D15, C1D22, C2D1, C2D15, C3D1, C3D15, C4D1, C4D15, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1; End of treatment (EOT [30 days after last drug administration])
Secondary outcome [17] 0 0
PK Parameter: Accumulation Ratio of Isatuximab at Trough Concentration (Ctrough)
Timepoint [17] 0 0
Pre-infusion on Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 4 Day 1
Secondary outcome [18] 0 0
Number of Participants With Anti-drug Antibodies (ADA)
Timepoint [18] 0 0
From randomization up to 60 days after last dose of study drug (maximum duration 76.7 weeks)
Secondary outcome [19] 0 0
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 (GHS)/Quality of Life (QOL) Score
Timepoint [19] 0 0
Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)
Secondary outcome [20] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Disease Symptoms Domain Score
Timepoint [20] 0 0
Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)
Secondary outcome [21] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Side Effects of Treatment Domain Score
Timepoint [21] 0 0
Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)
Secondary outcome [22] 0 0
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health State Utility Index Value
Timepoint [22] 0 0
Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)
Secondary outcome [23] 0 0
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)
Timepoint [23] 0 0
Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)

Eligibility
Key inclusion criteria
Inclusion criteria :

* Age superior or equal to 18 years or country's legal age of majority if the legal age was superior to 18 years old.
* Participants had a documented diagnosis of multiple myeloma with evidence of measurable disease i.e. serum M protein superior or equal to 0.5 grams per decilitre (g/dL) measured using serum protein immunoelectrophoresis and or urine M protein superior or equal to 200 mg per 24 hours measured using urine protein immunoelectrophoresis.
* Participants had received at least 2 prior lines of anti-myeloma therapy, which must include at least 2 consecutive cycles of lenalidomide and a proteasome inhibitor (bortezomib, carfilzomib or ixazomib) given alone or in combination.
* Participants had failed treatment with lenalidomide and a proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) alone or in combination (Intolerant, progression within 6 months after reaching Partial Response or better).
* Participants had progressed on or within 60 days after end of previous therapy before to study entry, i.e., refractory to the last line of treatment.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* Primary refractory multiple myeloma defined as participants who had never achieved at least a minimal response (MR) with any treatment during the disease course.
* Free Light Chain measurable disease only.
* Prior therapy with pomalidomide.
* Any anti-myeloma drug treatment within 14 days before randomization, including dexamethasone.
* Eastern Cooperative Oncology Group performance status superior to 2.
* Platelets inferior to 75 000 cells per microliter (mcL) if inferior to 50% of bone marrow (BM) nucleated cells are plasma cells, and inferior to 30 000 cells per mcL if superior or equal to 50% of BM nucleated cells are plasma cells. Platelet transfusion was not allowed within three days before the screening visit.
* Absolute neutrophil count inferior to 1000 per mcL (1*10^9/L).
* Creatinine clearance inferior to 30 mL per minute (Modification of Diet in Renal Disease [MDRD] Formula).
* Total bilirubin superior to 2*ULN (Upper Limit of Normal).
* Corrected serum calcium superior to 14 milligrams per deciliter (mg/dL) (superior to 3.5 millimoles per liter (mmol/L).
* Aspartate aminotransferase (AST) and/or Alanine Aminotransferase (ALT) superior to 3*ULN.
* Hypersensitivity to immunomodulatory drugs (IMiDs) (thalidomide or lenalidomide) defined as any hypersensitivity reaction leading to stop IMiDs within the 2 first cycles or toxicity, which does meet intolerance definition.
* Hypersensitivity to dexamethasone, sucrose histidine (as base and hydrochloride salt), and polysorbate 80 or any of the components of study therapy that are not amenable to premedication with steroids, or H2 blockers that would prohibit further treatment with these agents.
* Significant cardiac dysfunction; myocardial infarction within 12 months; unstable, poorly controlled angina pectoris.
* Pregnant or breastfeeding woman or female who intends to become pregnant during the participation in the study.
* Male participants who disagreed to practice true abstinence or disagreed to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and at least 3 or 5 months following study treatment discontinuation, even if he had undergone a successful vasectomy.
* All participants who disagreed to refrain from donating blood while on study treatment and for 4 weeks after discontinuation from this study treatment.

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/12/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2023
Sample size
Target
Accrual to date
Final
307
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Investigational Site Number : 0360004 - St Leonards
Recruitment hospital [2] 0 0
Investigational Site Number : 0360001 - Waratah
Recruitment hospital [3] 0 0
Investigational Site Number : 0360005 - Melbourne
Recruitment hospital [4] 0 0
Investigational Site Number : 0360002 - Melbourne
Recruitment hospital [5] 0 0
Investigational Site Number : 0360006 - Richmond
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
3121 - Richmond
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
Belgium
State/province [3] 0 0
Antwerpen
Country [4] 0 0
Belgium
State/province [4] 0 0
Brussel
Country [5] 0 0
Belgium
State/province [5] 0 0
Gent
Country [6] 0 0
Belgium
State/province [6] 0 0
Leuven
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
Czechia
State/province [8] 0 0
Brno
Country [9] 0 0
Czechia
State/province [9] 0 0
Hradec Kralove
Country [10] 0 0
Czechia
State/province [10] 0 0
Olomouc
Country [11] 0 0
Czechia
State/province [11] 0 0
Ostrava - Poruba
Country [12] 0 0
Czechia
State/province [12] 0 0
Praha 2
Country [13] 0 0
Denmark
State/province [13] 0 0
Aalborg
Country [14] 0 0
France
State/province [14] 0 0
Bayonne
Country [15] 0 0
France
State/province [15] 0 0
Caen
Country [16] 0 0
France
State/province [16] 0 0
Dijon
Country [17] 0 0
France
State/province [17] 0 0
Grenoble
Country [18] 0 0
France
State/province [18] 0 0
La Roche Sur Yon
Country [19] 0 0
France
State/province [19] 0 0
Lille
Country [20] 0 0
France
State/province [20] 0 0
Limoges
Country [21] 0 0
France
State/province [21] 0 0
Montpellier Cedex
Country [22] 0 0
France
State/province [22] 0 0
Nantes
Country [23] 0 0
France
State/province [23] 0 0
Paris
Country [24] 0 0
France
State/province [24] 0 0
Pessac
Country [25] 0 0
France
State/province [25] 0 0
Pierre Benite
Country [26] 0 0
France
State/province [26] 0 0
POITIERS Cedex
Country [27] 0 0
France
State/province [27] 0 0
Reims
Country [28] 0 0
France
State/province [28] 0 0
Rennes
Country [29] 0 0
France
State/province [29] 0 0
TOULOUSE Cedex 9
Country [30] 0 0
France
State/province [30] 0 0
Tours
Country [31] 0 0
France
State/province [31] 0 0
Vandoeuvre-les-nancy
Country [32] 0 0
Germany
State/province [32] 0 0
Leipzig
Country [33] 0 0
Greece
State/province [33] 0 0
Athens
Country [34] 0 0
Greece
State/province [34] 0 0
Patra
Country [35] 0 0
Greece
State/province [35] 0 0
Thessaloniki
Country [36] 0 0
Hungary
State/province [36] 0 0
Budapest
Country [37] 0 0
Hungary
State/province [37] 0 0
Debrecen
Country [38] 0 0
Italy
State/province [38] 0 0
Bologna
Country [39] 0 0
Italy
State/province [39] 0 0
Catania
Country [40] 0 0
Italy
State/province [40] 0 0
Firenze
Country [41] 0 0
Italy
State/province [41] 0 0
Genova
Country [42] 0 0
Italy
State/province [42] 0 0
Milano
Country [43] 0 0
Italy
State/province [43] 0 0
Padova
Country [44] 0 0
Italy
State/province [44] 0 0
Terni
Country [45] 0 0
Italy
State/province [45] 0 0
Torino
Country [46] 0 0
Japan
State/province [46] 0 0
Aichi
Country [47] 0 0
Japan
State/province [47] 0 0
Gunma
Country [48] 0 0
Japan
State/province [48] 0 0
Hokkaido
Country [49] 0 0
Japan
State/province [49] 0 0
Kyoto
Country [50] 0 0
Japan
State/province [50] 0 0
Nagano
Country [51] 0 0
Japan
State/province [51] 0 0
Okayama
Country [52] 0 0
Japan
State/province [52] 0 0
Sunto Gun
Country [53] 0 0
Japan
State/province [53] 0 0
Tokyo
Country [54] 0 0
Korea, Republic of
State/province [54] 0 0
Jeollanam-do
Country [55] 0 0
Korea, Republic of
State/province [55] 0 0
Seoul-teukbyeolsi
Country [56] 0 0
Korea, Republic of
State/province [56] 0 0
Incheon
Country [57] 0 0
Korea, Republic of
State/province [57] 0 0
Seoul
Country [58] 0 0
New Zealand
State/province [58] 0 0
Auckland
Country [59] 0 0
New Zealand
State/province [59] 0 0
Otago
Country [60] 0 0
New Zealand
State/province [60] 0 0
Waikato
Country [61] 0 0
Norway
State/province [61] 0 0
Oslo
Country [62] 0 0
Poland
State/province [62] 0 0
Lubuskie
Country [63] 0 0
Poland
State/province [63] 0 0
Malopolskie
Country [64] 0 0
Poland
State/province [64] 0 0
Mazowieckie
Country [65] 0 0
Poland
State/province [65] 0 0
Slaskie
Country [66] 0 0
Portugal
State/province [66] 0 0
Coimbra
Country [67] 0 0
Portugal
State/province [67] 0 0
Lisboa
Country [68] 0 0
Portugal
State/province [68] 0 0
Porto
Country [69] 0 0
Russian Federation
State/province [69] 0 0
Moscow
Country [70] 0 0
Slovakia
State/province [70] 0 0
Bratislava
Country [71] 0 0
Spain
State/province [71] 0 0
A Coruña [La Coruña]
Country [72] 0 0
Spain
State/province [72] 0 0
Barcelona [Barcelona]
Country [73] 0 0
Spain
State/province [73] 0 0
Cantabria
Country [74] 0 0
Spain
State/province [74] 0 0
Navarra
Country [75] 0 0
Spain
State/province [75] 0 0
Madrid
Country [76] 0 0
Spain
State/province [76] 0 0
Salamanca
Country [77] 0 0
Sweden
State/province [77] 0 0
Luleå
Country [78] 0 0
Sweden
State/province [78] 0 0
Uddevalla
Country [79] 0 0
Taiwan
State/province [79] 0 0
Kaohsiung
Country [80] 0 0
Taiwan
State/province [80] 0 0
Taichung
Country [81] 0 0
Taiwan
State/province [81] 0 0
Taipei
Country [82] 0 0
Taiwan
State/province [82] 0 0
Taoyuan
Country [83] 0 0
Turkey
State/province [83] 0 0
Ankara
Country [84] 0 0
Turkey
State/province [84] 0 0
Antalya
Country [85] 0 0
Turkey
State/province [85] 0 0
Istanbul
Country [86] 0 0
Turkey
State/province [86] 0 0
Izmir
Country [87] 0 0
Turkey
State/province [87] 0 0
Kayseri
Country [88] 0 0
Turkey
State/province [88] 0 0
Kocaeli
Country [89] 0 0
United Kingdom
State/province [89] 0 0
London, City Of

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02990338