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

Primary Purpose

Relapsed/Refractory Multiple Myeloma

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Isatuximab
Carfilzomib
Dexamethasone
Dexamethasone IV
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed/Refractory Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site Number :0360002Recruiting
  • Investigational Site Number :0360001Recruiting
  • Investigational Site Number :0760002Recruiting
  • Investigational Site Number :0760003Recruiting
  • Investigational Site Number :0760001Recruiting
  • Investigational Site Number :3000001Recruiting
  • Investigational Site Number :3000002Recruiting
  • Investigational Site Number :3920001Recruiting
  • Investigational Site Number :3920002Recruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1: manual administration

Part 1 Cohort 2: manual administration

Part 2 Randomized Cohort: OBDS to manual

Part 2 Randomized Cohort: Manual to OBDS

Arm Description

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.

Isatuximab will be administered manually for 6 minutes on Day 1 of Cycle 1 and thereafter.

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.

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.

Outcomes

Primary Outcome Measures

Overall response rate (ORR)
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).

Secondary Outcome Measures

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).
Incidence rate of infusion reactions (IRs)
Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and changes in laboratory parameters
Incidence rate of injection site reactions (ISRs)
PK concentration: trough plasma concentration (Ctrough)
Blood samples will be collected for measurement of isatuximab concentrations.
Proportion of participants with sCR, CR, VGPR, and PR according to the 2016 IMWG criteria assessed by IRC
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.
Time to first response (TT1R)
TT1R defined as time from randomization to first IRC determined response (PR or better) that is subsequently confirmed.
Time to best response (TTBR)
TTBR defined as time from randomization to first occurrence of IRC determined best response (PR or better) that is subsequently confirmed.
Progression free survival (PFS)
PFS defined as time from the date of randomization to the date of first documentation of PD as determined by IRC or the date of death from any cause, whichever comes first.
Overall survival (OS)
OS defined as time from the date of randomization to death from any cause
Incidence of participants with anti-drug antibodies (ADA) against isatuximab
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).
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.
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. The data collected include number, nature (emergency or routine) and duration of hospitalizations, emergency room visits and outpatient medical encounters and employment history.
Health Related Quality of Life (HRQL)
HRQL is assessed 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.
European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)
Health status is assessed 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.

Full Information

First Posted
January 20, 2023
Last Updated
September 29, 2023
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT05704049
Brief Title
A Study to Investigate Subcutaneous Isatuximab in Combination With Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
September 30, 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 5, 2023 (Actual)
Primary Completion Date
June 20, 2024 (Anticipated)
Study Completion Date
October 12, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
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. After confirmation of the feasibility of SC isatuximab by manual administration, patient will be randomized to 1 of the 2 delivery method of SC isatuximab.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/Refractory Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
68 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: manual administration
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 1 Cohort 2: manual administration
Arm Type
Experimental
Arm Description
Isatuximab will be administered manually for 6 minutes on Day 1 of Cycle 1 and thereafter.
Arm Title
Part 2 Randomized Cohort: OBDS to manual
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 2 Randomized Cohort: Manual to OBDS
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Isatuximab
Intervention Description
Pharmaceutical form: Solution for Subcutaneous administration; Route of administration: Subcutaneous
Intervention Type
Drug
Intervention Name(s)
Carfilzomib
Other Intervention Name(s)
Kyprolis
Intervention Description
Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Pharmaceutical form: Tablet; Route of administration: Oral
Intervention Type
Drug
Intervention Name(s)
Dexamethasone IV
Intervention Description
Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous
Primary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
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).
Time Frame
6 months after the Last Participant In (LPI) i.e., approximately 16 months
Secondary Outcome Measure Information:
Title
Proportion of participants preferring OBDS over manual administration of isatuximab SC at Day 15 of Cycle 6
Description
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).
Time Frame
6 months from LPI i.e., approximately 16 months
Title
Incidence rate of infusion reactions (IRs)
Time Frame
18 months after LPI i.e., approximately 28 months
Title
Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and changes in laboratory parameters
Time Frame
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
Title
Incidence rate of injection site reactions (ISRs)
Time Frame
18 months after LPI i.e., approximately 28 months
Title
PK concentration: trough plasma concentration (Ctrough)
Description
Blood samples will be collected for measurement of isatuximab concentrations.
Time Frame
Cycle 2 Day 1 and Cycle 6 Day 1 (1 Cycle = 28 days)
Title
Proportion of participants with sCR, CR, VGPR, and PR according to the 2016 IMWG criteria assessed by IRC
Time Frame
18 months after LPI i.e., approximately 28 months
Title
Duration of response (DOR)
Description
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.
Time Frame
18 months after LPI i.e., approximately 28 months
Title
Time to first response (TT1R)
Description
TT1R defined as time from randomization to first IRC determined response (PR or better) that is subsequently confirmed.
Time Frame
18 months after LPI i.e., approximately 28 months
Title
Time to best response (TTBR)
Description
TTBR defined as time from randomization to first occurrence of IRC determined best response (PR or better) that is subsequently confirmed.
Time Frame
18 months after LPI i.e., approximately 28 months
Title
Progression free survival (PFS)
Description
PFS defined as time from the date of randomization to the date of first documentation of PD as determined by IRC or the date of death from any cause, whichever comes first.
Time Frame
18 months after LPI i.e., approximately 28 months
Title
Overall survival (OS)
Description
OS defined as time from the date of randomization to death from any cause
Time Frame
18 months after LPI i.e., approximately 28 months
Title
Incidence of participants with anti-drug antibodies (ADA) against isatuximab
Time Frame
From Cycle 1 Day 1 to follow-up (90 days from last administration) i.e., approximately 13 months (1 Cycle = 28 days)
Title
Patient Expectations Questionnaire at Baseline (PEQ-BL v2) with isatuximab administered subcutaneously
Description
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).
Time Frame
Baseline
Title
Patient experience and satisfaction questionnaires (PESQ v2) with isatuximab administered subcutaneously
Description
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.
Time Frame
18 months after LPI i.e., approximately 28 months
Title
Health state utility assessed using Health Resource Utilization and Productivity Questionnaire (HRUPQ)
Description
Medical resource utilization and participant productivity will be collected from participants through a specific questionnaire developed by Sanofi. The data collected include number, nature (emergency or routine) and duration of hospitalizations, emergency room visits and outpatient medical encounters and employment history.
Time Frame
18 months after LPI i.e., approximately 28 months
Title
Health Related Quality of Life (HRQL)
Description
HRQL is assessed 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.
Time Frame
18 months after LPI i.e., approximately 28 months
Title
European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)
Description
Health status is assessed 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.
Time Frame
18 months after LPI i.e., approximately 28 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Trial Transparency email recommended (Toll free for US & Canada)
Phone
800-633-1610
Ext
option 6
Email
Contact-US@sanofi.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number :0360002
City
Wollongong
State/Province
New South Wales
ZIP/Postal Code
2500
Country
Australia
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :0360001
City
Fitzroy
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :0760002
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90110-270
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :0760003
City
Sao Paulo
State/Province
São Paulo
ZIP/Postal Code
04537-081
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :0760001
City
Sao Paulo
State/Province
São Paulo
ZIP/Postal Code
05403-000
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :3000001
City
Athens
ZIP/Postal Code
10676
Country
Greece
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :3000002
City
Athens
ZIP/Postal Code
11528
Country
Greece
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :3920001
City
Kashiwa-shi
State/Province
Chiba
ZIP/Postal Code
277-8577
Country
Japan
Individual Site Status
Recruiting
Facility Name
Investigational Site Number :3920002
City
Okayama-shi
State/Province
Okayama
ZIP/Postal Code
701-1192
Country
Japan
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

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

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