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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02990338
Ethics application status
Date submitted
4/12/2016
Date registered
13/12/2016
Date last updated
6/06/2019

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
2016-003097-41
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 SAR650984
Treatment: Drugs - pomalidomide
Treatment: Drugs - dexamethasone

Experimental: IPd (Isatuximab + Pomalidomide + Dexamethasone) - Isatuximab (intravenous) on Day 1, 8, 15, and 22 of 1st 28-day cycle, then on Day 1 and 15 of subsequent cycles in combination with pomalidomide per os on Day 1 to 21 + dexamethasone IV (intravenous) or per os on Day 1, 8, 15, 22 in 28-day cycles up to disease progression

Active Comparator: Pd (Pomalidomide + Dexamethasone) - Pomalidomide per os on Day 1 to 21 + dexamethasone IV (intravenous) or per os on Day 1, 8, 15, 22 in 28-day cycles up to disease progression


Treatment: Drugs: isatuximab SAR650984
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, whichever comes first, assessed approximatively up to 18 months
Secondary outcome [1] 0 0
Overall Response Rate (ORR)
Timepoint [1] 0 0
From the date of randomization to the date of first documentation of progression, assessed approximately up to 18 months
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
up to 51 months
Secondary outcome [3] 0 0
Time to Progression (TTP)
Timepoint [3] 0 0
From the date of randomization to the date of first documentation of progression, assessed approximately up to 18 months
Secondary outcome [4] 0 0
Progression Free Survival in high risk cytogenetic population
Timepoint [4] 0 0
From the date of randomization to the date of first documentation of progression or the date of death from any cause, whichever comes first, assessed approximately up to 18 months
Secondary outcome [5] 0 0
Duration of response
Timepoint [5] 0 0
From the date of randomization to the date of first documentation of progression or the date of death from any cause, whichever comes first, assessed approximately up to 18 months
Secondary outcome [6] 0 0
Number of patients with adverse events according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 grade scaling
Timepoint [6] 0 0
Up to 30 days after last study treatment administration
Secondary outcome [7] 0 0
Patient-reported outcome measured with Quality of Life questionnaire EORTC-QLQ-C30
Timepoint [7] 0 0
Approximately up to 18 months
Secondary outcome [8] 0 0
Patient-reported outcome measured with Quality of Life questionnaire MY20
Timepoint [8] 0 0
Approximately up to 18 months
Secondary outcome [9] 0 0
Patient-reported outcome measured with Quality of Life questionnaire EQ-5D-5L
Timepoint [9] 0 0
Approximately up to 18 months
Secondary outcome [10] 0 0
Plasma concentrations of isatuximab (IPd Arm)
Timepoint [10] 0 0
Up to 30 days after last study treatment administration
Secondary outcome [11] 0 0
Immune response (IPd Arm) : levels of human anti-drug antibodies (ADA)
Timepoint [11] 0 0
Up to 60 days after last study treatment administration, or until test is negative whichever comes last

Eligibility
Key inclusion criteria
Inclusion criteria :

- Age superior or equal to 18 years or country's legal age of majority if the legal age
is superior to 18 years old.

- Patients must have a documented diagnosis of multiple myeloma with evidence of
measurable disease i.e. serum M protein superior or equal to 0.5 g per 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.

- Patients must have 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.

- Patients must have failed treatment with lenalidomide and a proteasome inhibitor
(bortezomib, carfilzomib, or ixazomib) alone or in combination.

- Patients must have 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
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Primary refractory multiple myeloma defined as patients who have 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 µL if inferior to 50% of bone marrow (BM)
nucleated cells are plasma cells, and inferior to 30 000 cells per µL if superior or
equal to 50% of BM nucleated cells are plasma cells. Platelet transfusion is not
allowed within three days before the screening visit.

- Absolute neutrophils count inferior to 1000 per µL (1 x 10E9/L). The use of G-CSF is
not allowed to reach this level.

- Creatinine clearance inferior to 30 mL per min (MDRD Formula).

- Total bilirubin superior to 2 x ULN (Upper Limit of Normal).

- Corrected serum calcium superior to 14 mg per dL (superior to 3.5 mmol per L).

- Aspartate aminotransferase (AST) and/or Alanine Aminotransferase (ALT) superior to 3 x
ULN.

- Hypersensitivity to 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 disagree to practice true abstinence or disagree 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 months
following study treatment discontinuation, even if he has undergone a successful
vasectomy.

- All patients who disagree to refrain from donating blood while on study treatment and
for 4 weeks after discontinuation from this study treatment.

The above information is not intended to contain all considerations relevant to a patient'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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 0360005 - Melbourne
Recruitment hospital [2] 0 0
Investigational Site Number 0360002 - Prahran
Recruitment hospital [3] 0 0
Investigational Site Number 0360006 - Richmond
Recruitment hospital [4] 0 0
Investigational Site Number 0360004 - St Leonards
Recruitment hospital [5] 0 0
Investigational Site Number 0360001 - Waratah
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
3004 - Prahran
Recruitment postcode(s) [3] 0 0
3121 - Richmond
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment postcode(s) [5] 0 0
2298 - Waratah
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
Montreal
Country [8] 0 0
Canada
State/province [8] 0 0
Sherbrooke
Country [9] 0 0
Czechia
State/province [9] 0 0
Brno
Country [10] 0 0
Czechia
State/province [10] 0 0
Hradec Kralove
Country [11] 0 0
Czechia
State/province [11] 0 0
Olomouc
Country [12] 0 0
Czechia
State/province [12] 0 0
Ostrava - Poruba
Country [13] 0 0
Czechia
State/province [13] 0 0
Praha 2
Country [14] 0 0
Denmark
State/province [14] 0 0
Ålborg
Country [15] 0 0
France
State/province [15] 0 0
Bayonne
Country [16] 0 0
France
State/province [16] 0 0
Caen
Country [17] 0 0
France
State/province [17] 0 0
Dijon
Country [18] 0 0
France
State/province [18] 0 0
Grenoble
Country [19] 0 0
France
State/province [19] 0 0
La Roche Sur Yon
Country [20] 0 0
France
State/province [20] 0 0
Lille
Country [21] 0 0
France
State/province [21] 0 0
Limoges
Country [22] 0 0
France
State/province [22] 0 0
Montpellier Cedex
Country [23] 0 0
France
State/province [23] 0 0
Nantes Cedex 01
Country [24] 0 0
France
State/province [24] 0 0
Paris
Country [25] 0 0
France
State/province [25] 0 0
Pessac
Country [26] 0 0
France
State/province [26] 0 0
Pierre Benite
Country [27] 0 0
France
State/province [27] 0 0
Poitiers
Country [28] 0 0
France
State/province [28] 0 0
Reims
Country [29] 0 0
France
State/province [29] 0 0
Rennes
Country [30] 0 0
France
State/province [30] 0 0
Toulouse Cedex 9
Country [31] 0 0
France
State/province [31] 0 0
Tours
Country [32] 0 0
France
State/province [32] 0 0
Vandoeuvre-Les-Nancy
Country [33] 0 0
Germany
State/province [33] 0 0
Leipzig
Country [34] 0 0
Greece
State/province [34] 0 0
Athens
Country [35] 0 0
Greece
State/province [35] 0 0
Patra
Country [36] 0 0
Greece
State/province [36] 0 0
Thessaloniki
Country [37] 0 0
Hungary
State/province [37] 0 0
Budapest
Country [38] 0 0
Hungary
State/province [38] 0 0
Debrecen
Country [39] 0 0
Italy
State/province [39] 0 0
Bologna
Country [40] 0 0
Italy
State/province [40] 0 0
Catania
Country [41] 0 0
Italy
State/province [41] 0 0
Firenze
Country [42] 0 0
Italy
State/province [42] 0 0
Genova
Country [43] 0 0
Italy
State/province [43] 0 0
Milano
Country [44] 0 0
Italy
State/province [44] 0 0
Padova
Country [45] 0 0
Italy
State/province [45] 0 0
Terni
Country [46] 0 0
Italy
State/province [46] 0 0
Torino
Country [47] 0 0
Japan
State/province [47] 0 0
Kyoto-Shi
Country [48] 0 0
Japan
State/province [48] 0 0
Nagoya-Shi
Country [49] 0 0
Japan
State/province [49] 0 0
Okayama-Shi
Country [50] 0 0
Japan
State/province [50] 0 0
Sapporo-Shi
Country [51] 0 0
Japan
State/province [51] 0 0
Shibukawa-Shi
Country [52] 0 0
Japan
State/province [52] 0 0
Shibuya-Ku
Country [53] 0 0
Japan
State/province [53] 0 0
Sunto-Gun
Country [54] 0 0
Japan
State/province [54] 0 0
Suwa-Shi
Country [55] 0 0
Korea, Republic of
State/province [55] 0 0
Hwasun-Gun
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
Dunedin
Country [60] 0 0
New Zealand
State/province [60] 0 0
Hamilton
Country [61] 0 0
New Zealand
State/province [61] 0 0
Takapuna
Country [62] 0 0
Norway
State/province [62] 0 0
Oslo
Country [63] 0 0
Poland
State/province [63] 0 0
Chorzow
Country [64] 0 0
Poland
State/province [64] 0 0
Krakow
Country [65] 0 0
Poland
State/province [65] 0 0
Lublin
Country [66] 0 0
Poland
State/province [66] 0 0
Warszawa
Country [67] 0 0
Portugal
State/province [67] 0 0
Coimbra
Country [68] 0 0
Portugal
State/province [68] 0 0
Lisboa
Country [69] 0 0
Portugal
State/province [69] 0 0
Porto
Country [70] 0 0
Russian Federation
State/province [70] 0 0
Moscow
Country [71] 0 0
Slovakia
State/province [71] 0 0
Bratislava
Country [72] 0 0
Spain
State/province [72] 0 0
Barcelona
Country [73] 0 0
Spain
State/province [73] 0 0
Madrid
Country [74] 0 0
Spain
State/province [74] 0 0
Pamplona
Country [75] 0 0
Spain
State/province [75] 0 0
Salamanca
Country [76] 0 0
Spain
State/province [76] 0 0
Santander
Country [77] 0 0
Spain
State/province [77] 0 0
Santiago De Compostela
Country [78] 0 0
Sweden
State/province [78] 0 0
Luleå
Country [79] 0 0
Sweden
State/province [79] 0 0
Uddevalla
Country [80] 0 0
Taiwan
State/province [80] 0 0
Kaohsiung
Country [81] 0 0
Taiwan
State/province [81] 0 0
Taichung
Country [82] 0 0
Taiwan
State/province [82] 0 0
Taipei
Country [83] 0 0
Taiwan
State/province [83] 0 0
Taoyuan
Country [84] 0 0
Turkey
State/province [84] 0 0
Ankara
Country [85] 0 0
Turkey
State/province [85] 0 0
Antalya
Country [86] 0 0
Turkey
State/province [86] 0 0
Istanbul
Country [87] 0 0
Turkey
State/province [87] 0 0
Izmir
Country [88] 0 0
Turkey
State/province [88] 0 0
Kayseri
Country [89] 0 0
Turkey
State/province [89] 0 0
Kocaeli
Country [90] 0 0
United Kingdom
State/province [90] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objective:

To demonstrate the benefit of isatuximab in combination with pomalidomide and low-dose
dexamethasone in the prolongation of Progression Free Survival (PFS) as compared to
pomalidomide and low-dose dexamethasone in patients with refractory or relapsed and
refractory multiple myeloma (MM).

Secondary Objectives:

- To evaluate the Overall Response Rate (ORR) as per International Myeloma Working Group
(IMWG) criteria in each arm.

- To compare the Overall Survival (OS) between the two arms.

- To evaluate the Time To Progression (TTP) in each arm.

- To evaluate the Progression Free Survival (PFS) in high risk cytogenetic population in
each arm.

- To evaluate the Duration of Response (DOR) in each arm.

- To evaluate the safety in both treatment arms.

- To determine the Pharmacokinetic profile of isatuximab in combination with pomalidomide.

- To evaluate the immunogenicity of isatuximab.

- To assess disease-specific and generic health-related quality of life (HRQL), disease
and treatment-related symptoms, health state utility, and health status.
Trial website
https://clinicaltrials.gov/show/NCT02990338
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

Summary results
Other publications