A Study to Investigate Subcutaneous Isatuximab in Combination With Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma (IZALCO)

A Randomized, Phase 2, Open Label Study Evaluating Subcutaneous Administration of Isatuximab in Combination With Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma (RRMM)

The main purpose of this study is to measure the efficacy (Myeloma response) of subcutaneous (SC) isatuximab treatment in combination with carfilzomib and dexamethasone in adult participants with RRMM having received 1 to 3 prior lines of therapy, and to characterize the PK of isatuximab in combination with carfilzomib and dexamethasone after manual and On Body Delivery System (OBDS) administration. After confirmation of the feasibility of SC isatuximab by manual administration, patient will be randomized to 1 of the 2 delivery methods of SC isatuximab.

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed/Refractory Multiple Myeloma
• Intervention / Treatment: Drug: Isatuximab; Drug: Carfilzomib; Drug: Dexamethasone; Drug: Dexamethasone IV; Drug: Montelukast; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Methylprednisolone

Detailed Description

The duration of the study for a participant will include a period for screening of up to 28 days. A cycle duration is 28 days. Participants will be allowed to continue therapy until disease progression, unacceptable adverse events (AEs), participant request to discontinue treatment, or any other reason, as well as the study treatment is commercially available and reimbursed in the participant's country, or is available from another source, whichever is first. The overall study duration will be of approximately 45 months.

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Wollongong, New South Wales, Australia, 2500
      • Investigational Site Number : 0360002
  • Victoria
    • Melbourne, Victoria, Australia, 3065
      • Investigational Site Number : 0360001
• Brazil
  • São Paulo, Brazil, 04537-080
    • Clinica São Germano- Site Number : 0760003
  • São Paulo, Brazil, 05403-000
    • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo- Site Number : 0760001
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90880-480
      • Hospital Mae de Deus Site Number : 0760002
• China
  • Changsha, China, 410013
    • Investigational Site Number : 1560006
  • Guangzhou, China, 510060
    • Investigational Site Number : 1560002
  • Nanchang, China, 330006
    • Investigational Site Number : 1560005
  • Shenyang, China, 110004
    • Investigational Site Number : 1560004
  • Tianjin, China, 300020
    • Investigational Site Number : 1560001
  • Tianjin, China, 300060
    • Investigational Site Number : 1560007
  • Wuhan, China, 430030
    • Investigational Site Number : 1560003
• Czechia
  • Brno, Czechia, 625 00
    • Investigational Site Number : 2030002
  • Olomouc, Czechia, 779 00
    • Investigational Site Number : 2030004
  • Ostrava, Czechia, 708 52
    • Investigational Site Number : 2030003
  • Prague, Czechia, 128 08
    • Investigational Site Number : 2030001
• Greece
  • Athens, Greece, 106 76
    • Investigational Site Number : 3000001
  • Athens, Greece, 115 28
    • Investigational Site Number : 3000002
• Japan
  • Okayama, Japan, 701-1192
    • Investigational Site Number : 3920002
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Investigational Site Number : 3920001
• Portugal
  • Braga, Portugal, 4710-243
    • Investigational Site Number : 6200001
  • Lisbon, Portugal, 1400-038
    • Investigational Site Number : 6200004
  • Lisbon, Portugal, 1649-035
    • Investigational Site Number : 6200005

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants must have a documented diagnosis of multiple myeloma (MM)

• Participants with measurable disease defined as at least one of the following:

  • Serum M-protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or
  • Urine M-protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis and/or
  • Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).
• Participant with relapsed and/or refractory MM with at least 1 prior line of therapy and no more than 3 prior lines of therapy.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and either is not a female of childbearing potential (FCBP) or agrees to practice complete abstinence or use approved contraception methods.
• Male participants agree to practice true abstinence or agree to use approved contraception methods while receiving study treatment, during dose interruptions and at least 5 months following study treatment discontinuation, even if has undergone a successful vasectomy.
• Capable of giving signed informed consent.

Exclusion Criteria:

• Primary refractory MM defined as participants who have never achieved at least a minimal response (MR) with any treatment during the disease course
• Participants with prior anti-CD38 treatment if: a) administered <9 months before first isatuximab administration or randomization as applicable or, b) Intolerant to the anti-CD38 previously received
• Prior treatment with carfilzomib
• Known history of allergy to captisol (a cyclodextrin derivative used to solubilize carfilzomib), prior hypersensitivity to sucrose, histidine (as base and hydrochloride salt), polysorbate 80, or any of the components (active substance or excipient) of study treatment that are not amenable to premedication with steroids, or intolerance to arginine and Poloxamer 188 that would prohibit further treatment with these agents
• Uncontrolled or active infection with hepatitis A, B, and C virus; known acquired immunodeficiency syndrome (AIDS)-related illness; active primary amyloid light chain (AL) amyloidosis
• Any severe acute or chronic medical condition which could impair the ability of the participant to participate in the study or interfere with interpretation of study results (eg, systemic infection unless specific anti-infective therapy is employed) or participant unable to comply with the study procedures.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: manual administration; Isatuximab will be administered manually for 8 minutes on Day 1 of Cycle 1 followed by 6 minutes from Day 8 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.	Drug: Isatuximab; Investigational medicinal product; Pharmaceutical form: Solution for Subcutaneous administration; Route of administration: Subcutaneous; Drug: Carfilzomib; Investigational medicinal product; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous; Other Names: Kyprolis; Drug: Dexamethasone; Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Tablet; Route of administration: Oral; Drug: Dexamethasone IV; Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous; Drug: Montelukast; Background Treatment; ATC code: R03DC03; Pharmaceutical form: As per local commercial product; Route of administration: Oral; Drug: Acetaminophen; Background Treatment; ATC code: N02BE01; Pharmaceutical form: As per local commercial product; Route of administration: Oral or intravenous (IV); Drug: Diphenhydramine; Background Treatment; ATC code: R06AA02; Pharmaceutical form: As per local commercial product; Route of administration: Oral or IV; Drug: Methylprednisolone; Background Treatment/Rescue medication; ATC code: H02AB04; Pharmaceutical form: As per local commercial product; Route of administration: IV
Experimental: Part 1 Cohort 2: manual administration; Isatuximab will be administered manually for 6 minutes on Day 1 of Cycle 1 and thereafter, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.	Drug: Isatuximab; Investigational medicinal product; Pharmaceutical form: Solution for Subcutaneous administration; Route of administration: Subcutaneous; Drug: Carfilzomib; Investigational medicinal product; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous; Other Names: Kyprolis; Drug: Dexamethasone; Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Tablet; Route of administration: Oral; Drug: Dexamethasone IV; Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous; Drug: Montelukast; Background Treatment; ATC code: R03DC03; Pharmaceutical form: As per local commercial product; Route of administration: Oral; Drug: Acetaminophen; Background Treatment; ATC code: N02BE01; Pharmaceutical form: As per local commercial product; Route of administration: Oral or intravenous (IV); Drug: Diphenhydramine; Background Treatment; ATC code: R06AA02; Pharmaceutical form: As per local commercial product; Route of administration: Oral or IV; Drug: Methylprednisolone; Background Treatment/Rescue medication; ATC code: H02AB04; Pharmaceutical form: As per local commercial product; Route of administration: IV
Experimental: Part 2 Cohort 3 Randomized Cohort: OBDS to manual; Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.	Drug: Isatuximab; Investigational medicinal product; Pharmaceutical form: Solution for Subcutaneous administration; Route of administration: Subcutaneous; Drug: Carfilzomib; Investigational medicinal product; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous; Other Names: Kyprolis; Drug: Dexamethasone; Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Tablet; Route of administration: Oral; Drug: Dexamethasone IV; Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous; Drug: Montelukast; Background Treatment; ATC code: R03DC03; Pharmaceutical form: As per local commercial product; Route of administration: Oral; Drug: Acetaminophen; Background Treatment; ATC code: N02BE01; Pharmaceutical form: As per local commercial product; Route of administration: Oral or intravenous (IV); Drug: Diphenhydramine; Background Treatment; ATC code: R06AA02; Pharmaceutical form: As per local commercial product; Route of administration: Oral or IV; Drug: Methylprednisolone; Background Treatment/Rescue medication; ATC code: H02AB04; Pharmaceutical form: As per local commercial product; Route of administration: IV
Experimental: Part 2 Cohort 3 Randomized Cohort: Manual to OBDS; Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.	Drug: Isatuximab; Investigational medicinal product; Pharmaceutical form: Solution for Subcutaneous administration; Route of administration: Subcutaneous; Drug: Carfilzomib; Investigational medicinal product; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous; Other Names: Kyprolis; Drug: Dexamethasone; Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Tablet; Route of administration: Oral; Drug: Dexamethasone IV; Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous; Drug: Montelukast; Background Treatment; ATC code: R03DC03; Pharmaceutical form: As per local commercial product; Route of administration: Oral; Drug: Acetaminophen; Background Treatment; ATC code: N02BE01; Pharmaceutical form: As per local commercial product; Route of administration: Oral or intravenous (IV); Drug: Diphenhydramine; Background Treatment; ATC code: R06AA02; Pharmaceutical form: As per local commercial product; Route of administration: Oral or IV; Drug: Methylprednisolone; Background Treatment/Rescue medication; ATC code: H02AB04; Pharmaceutical form: As per local commercial product; Route of administration: IV
Experimental: Part 3 Cohort 4 Randomized Cohort: OBDS to manual; Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.	Drug: Isatuximab; Investigational medicinal product; Pharmaceutical form: Solution for Subcutaneous administration; Route of administration: Subcutaneous; Drug: Carfilzomib; Investigational medicinal product; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous; Other Names: Kyprolis; Drug: Dexamethasone; Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Tablet; Route of administration: Oral; Drug: Dexamethasone IV; Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous; Drug: Montelukast; Background Treatment; ATC code: R03DC03; Pharmaceutical form: As per local commercial product; Route of administration: Oral; Drug: Acetaminophen; Background Treatment; ATC code: N02BE01; Pharmaceutical form: As per local commercial product; Route of administration: Oral or intravenous (IV); Drug: Diphenhydramine; Background Treatment; ATC code: R06AA02; Pharmaceutical form: As per local commercial product; Route of administration: Oral or IV; Drug: Methylprednisolone; Background Treatment/Rescue medication; ATC code: H02AB04; Pharmaceutical form: As per local commercial product; Route of administration: IV
Experimental: Part 3 Cohort 4: Randomized Cohort: manual to OBDS; Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.	Drug: Isatuximab; Investigational medicinal product; Pharmaceutical form: Solution for Subcutaneous administration; Route of administration: Subcutaneous; Drug: Carfilzomib; Investigational medicinal product; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous; Other Names: Kyprolis; Drug: Dexamethasone; Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Tablet; Route of administration: Oral; Drug: Dexamethasone IV; Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous; Drug: Montelukast; Background Treatment; ATC code: R03DC03; Pharmaceutical form: As per local commercial product; Route of administration: Oral; Drug: Acetaminophen; Background Treatment; ATC code: N02BE01; Pharmaceutical form: As per local commercial product; Route of administration: Oral or intravenous (IV); Drug: Diphenhydramine; Background Treatment; ATC code: R06AA02; Pharmaceutical form: As per local commercial product; Route of administration: Oral or IV; Drug: Methylprednisolone; Background Treatment/Rescue medication; ATC code: H02AB04; Pharmaceutical form: As per local commercial product; Route of administration: IV
Experimental: Part 3 Cohort 5 Randomized Cohort: OBDS to manual administration in Chinese participants; Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered via OBDS from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from OBDS to manual administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.	Drug: Isatuximab; Investigational medicinal product; Pharmaceutical form: Solution for Subcutaneous administration; Route of administration: Subcutaneous; Drug: Carfilzomib; Investigational medicinal product; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous; Other Names: Kyprolis; Drug: Dexamethasone; Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Tablet; Route of administration: Oral; Drug: Dexamethasone IV; Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous; Drug: Montelukast; Background Treatment; ATC code: R03DC03; Pharmaceutical form: As per local commercial product; Route of administration: Oral; Drug: Acetaminophen; Background Treatment; ATC code: N02BE01; Pharmaceutical form: As per local commercial product; Route of administration: Oral or intravenous (IV); Drug: Diphenhydramine; Background Treatment; ATC code: R06AA02; Pharmaceutical form: As per local commercial product; Route of administration: Oral or IV; Drug: Methylprednisolone; Background Treatment/Rescue medication; ATC code: H02AB04; Pharmaceutical form: As per local commercial product; Route of administration: IV
Experimental: Part 3 Cohort 5 Randomized Cohort: manual to OBDS administration in Chinese participants; Isatuximab will be administered in combination with carfilzomib and dexamethasone. Isatuximab will be administered manually from Cycle 1 to 3. For Cycle 4 to 6, the method of administration will be switched for each participant from manual to OBDS administration. From Cycle 7 and onwards, participants can choose manual or OBDS. Participants may receive other treatments as rescue medication or background medication.	Drug: Isatuximab; Investigational medicinal product; Pharmaceutical form: Solution for Subcutaneous administration; Route of administration: Subcutaneous; Drug: Carfilzomib; Investigational medicinal product; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous; Other Names: Kyprolis; Drug: Dexamethasone; Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Tablet; Route of administration: Oral; Drug: Dexamethasone IV; Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous; Drug: Montelukast; Background Treatment; ATC code: R03DC03; Pharmaceutical form: As per local commercial product; Route of administration: Oral; Drug: Acetaminophen; Background Treatment; ATC code: N02BE01; Pharmaceutical form: As per local commercial product; Route of administration: Oral or intravenous (IV); Drug: Diphenhydramine; Background Treatment; ATC code: R06AA02; Pharmaceutical form: As per local commercial product; Route of administration: Oral or IV; Drug: Methylprednisolone; Background Treatment/Rescue medication; ATC code: H02AB04; Pharmaceutical form: As per local commercial product; Route of administration: IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) - Cohorts 1 to 3	ORR defined as the proportion of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to the 2016 International Myeloma Working Group (IMWG) criteria assessed by Independent Review Committee (IRC).	6 months after the Last Participant In (LPI) i.e., approximately 16 months
Maximum observed concentration (Cmax) over Cycle 1- Cohorts 4 to 5		Cycle 1 (28 days)
Cumulative area under the curve over the first 4 weeks (AUC4weeks) of isatuximab treatment- Cohorts 4 to 5		Cycle 1 (28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants preferring OBDS over manual administration of isatuximab SC at Day 15 of Cycle 6	Patient preference for method of administration defined as the proportion of participants preferring OBDS over manual administration of isatuximab SC at Day 15 of Cycle 6 using the patient experience and satisfaction questionnaire version 2 (PESQ v2).	6 months from LPI i.e., approximately 16 months
Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and changes in laboratory parameters		From the signing of the informed consent to 30 days following the last administration of any study treatment i.e., up to approximately 45 months
Incidence rate of injection site reactions (ISRs)		18 months after LPI i.e., approximately 28 months
PK concentration: trough plasma concentration (Ctrough)	Blood samples will be collected for measurement of isatuximab concentrations.	Cycle 2 Day 1 and Cycle 6 Day 1 (1 Cycle = 28 days)
Incidence of participants with anti-drug antibodies (ADA) against isatuximab		From Cycle 1 Day 1 to follow-up (90 days from last administration) i.e., approximately 13 months (1 Cycle = 28 days)
Patient Expectations Questionnaire at Baseline (PEQ-BL v2) with isatuximab administered subcutaneously	PEQ-BL v2 is a participant assessed questionnaire. It will be completed at baseline prior to study treatment administration or other study related procedures. This questionnaire has been designed to assess the expectations of the participants regarding both the treatment (side effects, worth taking) and the administration method (confidence, comfortability, pain, side effects, potential time-savings), as well as to understand previous treatment experience from the participant (experience with injection methods for oncology medication).	Baseline
Patient experience and satisfaction questionnaires (PESQ v2) with isatuximab administered subcutaneously	PESQ v2 is a participant assessed questionnaire. It has been designed to follow up on participant experience and satisfaction regarding the treatment (side effects, worth taking and overall satisfaction) and the administration method (confidence, comfortability, pain, side effects, potential time-savings and overall satisfaction). The PESQ v2 includes items to assess preference on subcutaneous injection method. This questionnaire has been developed using industry standard for instrument development and has been debriefed and adapted based on qualitative interviews with oncology patients. The more general treatment expectations instrument (v1) was further adapted and debriefed with patients to assess manual and OBDS subcutaneous delivery (v2). The PESQ v2 contains a total of 9 items. There are 6 items that are administered for the duration of treatment, and 3 preference items administered only after patient experience of both manual and OBDS.	18 months after LPI i.e., approximately 28 months
Overall survival (OS)	OS defined as time from the date of first IMP administration or randomization to death from any cause.	18 months after LPI i.e., approximately 28 months
Incidence rate of infusion reactions (IRs)		From the signing of the informed consent to 30 days following the last administration of any study treatment i.e., up to approximately 45 months
Overall response rate (ORR)	Proportion of participants with sCR, CR, VGPR, and PR according to the 2016 IMWG criteria assessed by investigator.	6 months after the Last Participant In (LPI) i.e., approximately 16 months
Duration of response (DOR)	DOR defined as time from date of first IRC-determined response for participants achieving PR or better to first documentation of progressive disease (PD) determined by IRC or death, whichever occurred first, for Cohorts 1 to 3. For Cohorts 4-5, the time from date of first investigator determined response for participants achieving PR or better to first documentation of progressive disease (PD) determined by investigator or death, whichever occurred first.	6 months after the Last Participant In (LPI) i.e., approximately 16 months
Time to first response (TT1R)	TT1R defined as time from first investigational medicinal product (IMP) administration or randomization to first IRC determined response (PR or better) that is subsequently confirmed, for Cohorts 1 to 3. For cohorts 4-5, the time from first IMP administration or randomization to first investigator determined response (PR or better) that is subsequently confirmed.	6 months after the Last Participant In (LPI) i.e., approximately 16 months
Time to best response (TTBR)	TTBR defined as time from first IMP administration or randomization to first occurrence of IRC determined best response (PR or better) that is subsequently confirmed, for Cohorts 1 to 3. For cohorts 4-5, the time from first IMP administration or randomization to first occurrence of investigator determined best response (PR or better) that is subsequently confirmed.	6 months after the Last Participant In (LPI) i.e., approximately 16 months
Progression free survival (PFS)	PFS defined as time from the date of first IMP administration or randomization to the date of first documentation of PD as determined by IRC for Cohorts 1 to 3 and by Investigator for all cohorts, or the date of death from any cause, whichever comes first.	18 months after LPI i.e., approximately 28 months
Health state utility assessed using Health Resource Utilization and Productivity Questionnaire (HRUPQ)	Medical resource utilization and participant productivity will be collected from participants through a specific questionnaire developed by Sanofi for cohorts 1,2, 3, and 5. The data collected include number, nature (emergency or routine) and duration of hospitalizations, emergency room visits and outpatient medical encounters and employment history.	18 months after LPI i.e., approximately 28 months
Health Related Quality of Life (HRQL)	HRQL is assessed for cohorts 1, 2, and 3 using the European Organization for Research and Treatment of Cancer (EORTC) myeloma module with 20 items (QLQ-MY20) and EORTC quality of life questionnaire with 30 questions (QLQ-C30); a total of 50 items. The EORTC QLQ-C30 provides a comprehensive assessment of the principal HRQL dimensions identified as relevant by cancer patients. The EORTC QLQ-MY20 is to be used in conjunction with the EORTC QLQ-C30 to assess symptoms and side effects due to the treatment or the disease which impact HRQL in participants with MM.	18 months after LPI i.e., approximately 28 months
European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)	Health status is assessed for cohorts 1, 2, and 3, using the EQ-5D-5L, a standardized measure of health status that provides a simple, generic measure of health utility, and consists of 2 sections: descriptive and VAS. The descriptive system consists of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The VAS records the respondent's self-rated health on a 20 cm vertical VAS with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine'. This information can be used as a quantitative measure of health as judged by the individual respondents.	18 months after LPI i.e., approximately 28 months

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

General Publications

• Parmar G, Capra M, Seguro F, Hungria V, Dimopoulos MA, Delimpasi S, Minarik J, Spicka I, Pour L, Marques H, Esteves G, Sunami K, Yuda J, Hajek R, Mihalyova J, Soufflet C, Yu D, Benlhassan K, Koch V, Comerford E, Cordero P, Suzan F, Quach H. Efficacy and safety of isatuximab subcutaneous plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma: results of the Phase 2 study IZALCO. Blood Cancer J. 2025 Dec 27. doi: 10.1038/s41408-025-01436-0. Online ahead of print.

Helpful Links

• ACT17453 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2023
• Primary Completion (Actual): December 22, 2025
• Study Completion (Estimated): May 12, 2028

Study Registration Dates

• First Submitted: January 20, 2023
• First Submitted That Met QC Criteria: January 20, 2023
• First Posted (Actual): January 30, 2023

Study Record Updates

• Last Update Posted (Actual): December 29, 2025
• Last Update Submitted That Met QC Criteria: December 26, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzene Derivatives; Pregnadienetriols; Ethylamines; Prednisolone; Benzhydryl Compounds; Dexamethasone; Acetaminophen; Methylprednisolone; Diphenhydramine; carfilzomib; isatuximab; montelukast
• Other Study ID Numbers: ACT17453; U1111-1280-5090 (Registry Identifier: ICTRP); 2023-508870-27 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes