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History of Changes for Study: NCT02990338
Multinational Clinical Study Comparing Isatuximab, Pomalidomide, and Dexamethasone to Pomalidomide and Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma Patients (ICARIA-MM)
Latest version (submitted September 26, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 December 8, 2016 None (earliest Version on record)
2 December 21, 2016 Recruitment Status, Contacts/Locations and Study Status
3 January 11, 2017 Study Status and Contacts/Locations
4 April 10, 2017 Study Status and Contacts/Locations
5 April 27, 2017 Contacts/Locations and Study Status
6 May 11, 2017 Study Status and Contacts/Locations
7 June 12, 2017 Study Status and Contacts/Locations
8 June 26, 2017 Contacts/Locations and Study Status
9 June 28, 2017 Arms and Interventions, Study Status, IPDSharing, Outcome Measures and Study Description
10 July 10, 2017 Study Status and Contacts/Locations
11 August 2, 2017 Contacts/Locations and Study Status
12 August 21, 2017 Contacts/Locations and Study Status
13 September 4, 2017 Contacts/Locations and Study Status
14 September 14, 2017 Study Status and Contacts/Locations
15 October 3, 2017 Contacts/Locations and Study Status
16 October 10, 2017 Study Status and Contacts/Locations
17 October 18, 2017 Study Status
18 October 25, 2017 Study Status and Contacts/Locations
19 November 8, 2017 Study Status and Contacts/Locations
20 December 6, 2017 Study Status and Contacts/Locations
21 December 8, 2017 Study Status
22 December 20, 2017 Study Status and Contacts/Locations
23 January 8, 2018 Study Status
24 January 10, 2018 Contacts/Locations and Study Status
25 January 11, 2018 Study Status
26 January 24, 2018 Study Status and Contacts/Locations
27 February 7, 2018 Contacts/Locations and Study Status
28 February 22, 2018 Contacts/Locations and Study Status
29 March 8, 2018 Study Status and Contacts/Locations
30 March 27, 2018 Contacts/Locations and Study Status
31 April 3, 2018 Study Status
32 April 11, 2018 Contacts/Locations and Study Status
33 May 14, 2018 Contacts/Locations and Study Status
34 May 29, 2018 Contacts/Locations and Study Status
35 June 5, 2018 Recruitment Status, Study Status and Contacts/Locations
36 June 14, 2018 Study Status and Contacts/Locations
37 June 26, 2018 Contacts/Locations and Study Status
38 September 26, 2018 Contacts/Locations and Study Status
39 October 25, 2018 Study Status
40 November 8, 2018 Study Status
41 December 19, 2018 Study Status
42 January 11, 2019 Study Status
43 January 30, 2019 Contacts/Locations and Study Status
44 February 15, 2019 Study Status and Contacts/Locations
45 April 8, 2019 Study Status
46 April 18, 2019 Study Status
47 June 5, 2019 Study Status
48 November 19, 2019 Study Status, Outcome Measures, Arms and Interventions, Contacts/Locations, Study Design, Study Description, Document Section, Results and Eligibility
49 December 19, 2019 Study Status and References
50 January 14, 2020 Study Status
51 March 4, 2020 Contacts/Locations and Study Status
52 May 15, 2020 Study Status
53 May 29, 2020 Study Status
54 June 2, 2020 Study Status, Arms and Interventions and Conditions
55 June 17, 2020 Study Status
56 July 20, 2020 Study Status
57 July 21, 2020 Study Status
58 August 11, 2020 Study Status
59 September 28, 2020 Study Status
60 October 27, 2020 Study Status
61 February 23, 2021 Contacts/Locations and Study Status
62 September 27, 2021 Study Status
63 February 16, 2022 Contacts/Locations and Study Status
64 March 30, 2022 Study Status and IPDSharing
65 September 26, 2022 Study Status and Contacts/Locations
Comparison Format:

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Study NCT02990338
Submitted Date:  December 8, 2016 (v1)

Open or close this module Study Identification
Unique Protocol ID: EFC14335
Brief Title: Multinational Clinical Study Comparing Isatuximab, Pomalidomide, and Dexamethasone to Pomalidomide and Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma Patients (ICARIA-MM)
Official 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 IDs: 2016-003097-41 [EudraCT Number]
U1111-1180-6262 [UTN]
Open or close this module Study Status
Record Verification: December 2016
Overall Status: Not yet recruiting
Study Start: December 2016
Primary Completion: May 2018 [Anticipated]
Study Completion: April 2021 [Anticipated]
First Submitted: December 4, 2016
First Submitted that
Met QC Criteria:
December 8, 2016
First Posted: December 13, 2016 [Estimate]
Last Update Submitted that
Met QC Criteria:
December 8, 2016
Last Update Posted: December 13, 2016 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Sanofi
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
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.
Detailed Description:

The duration of the study for the patients will include a period for screening of up to 3 weeks. Patients will continue study treatment until disease progression, unacceptable adverse reaction, patients' wish or other reason of discontinuation.

During follow-up, patients who discontinue the study treatment due to progression of the disease will be followed every 3 months (12 weeks) for survival (or until cut- off date), and patients who discontinue the study treatment prior to documentation of disease progression will be followed-up every 4 weeks until disease progression, and then every 3 months (12 weeks) for survival (or until cut-off date).

Open or close this module Conditions
Conditions: Plasma Cell Myeloma
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 300 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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
Drug: isatuximab (EFC14335)
Pharmaceutical form:solution for infusion Route of administration: intravenous
Other Names:
  • SAR650984
Drug: pomalidomide
Pharmaceutical form:capsule Route of administration: oral
Drug: dexamethasone
Pharmaceutical form:tablets or solution for infusion Route of administration: oral or intravenous
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
Drug: pomalidomide
Pharmaceutical form:capsule Route of administration: oral
Drug: dexamethasone
Pharmaceutical form:tablets or solution for infusion Route of administration: oral or intravenous
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Progression Free Survival (PFS)
[ Time Frame: 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 Measures:
1. Overall Response Rate (ORR)
[ Time Frame: From the date of randomization to the date of first documentation of progression, assessed approximately up to 18 months ]

2. Overall Survival (OS)
[ Time Frame: up to 51 months ]

3. Time to Progression (TTP)
[ Time Frame: From the date of randomization to the date of first documentation of progression, assessed approximately up to 18 months ]

4. Progression Free Survival in high risk cytogenetic population
[ Time Frame: 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 ]

5. Duration of response
[ Time Frame: From the date of randomization to the date of first documentation of progression, assessed approximately up to 18 months ]

6. Number of patients with adverse events according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 grade scaling
[ Time Frame: Up to 30 days after last study treatment administration ]

7. Patient-reported outcome measured with Quality of Life questionnaire EORTC-QLQ-C30
[ Time Frame: Approximately up to 18 months ]

8. Patient-reported outcome measured with Quality of Life questionnaire MY20
[ Time Frame: Approximately up to 18 months ]

9. Patient-reported outcome measured with Quality of Life questionnaire EQ-5D-5L
[ Time Frame: Approximately up to 18 months ]

10. Plasma concentrations of isatuximab (IPd Arm)
[ Time Frame: Up to 30 days after last study treatment administration ]

11. Immune response (IPd Arm) : levels of human anti-drug antibodies (ADA)
[ Time Frame: Up to 60 days after last study treatment administration, or until test is negative whichever comes last ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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.

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.

Open or close this module Contacts/Locations
Central Contact Person: Trial Transparency Team
Email: Contact-US@sanofi.com
Study Officials: Clinical Sciences & Operations
Study Director
Sanofi
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

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