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)
A study to investigate subcutaneous isatuximab in combination with carfilzomib and dexamethasone in adult participants with relapsed and/or refractory multiple myeloma
Tanaka Tomoyuki
Sanofi K.K.
Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan
+81-3-6301-3670
clinical-trials-jp@sanofi.com
Clinical Study Unit
Sanofi K.K.
Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan
+81-3-6301-3670
clinical-trials-jp@sanofi.com
Not Recruiting
Mar. 29, 2023
Dec. 04, 2023
71
Interventional
randomized controlled trial
open(masking not used)
active control
parallel assignment
treatment purpose
- 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.
Participants are excluded from the study if any of the following criteria apply:
- 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 the potential participation in a clinical trial.
18age old over
No limit
Both
Relapsed/refractory multiple myeloma
Drug: Isatuximab
Pharmaceutical form: Solution for Subcutaneous administration, Route of administration: Subcutaneous
Drug: Carfilzomib
Pharmaceutical form: Powder for solution for infusion, Route of administration: Intravenous
Drug: Dexamethasone
Pharmaceutical form: Tablet, Route of administration: Oral
Drug: Dexamethasone IV
Pharmaceutical form: Powder for solution for infusion, Route of administration: Intravenous
1.Overall response rate (ORR)
[Time Frame baseline:6 months after the Last Participant In (LPI) i.e., approximately 16 months ]
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).
1.Proportion of participants preferring OBDS over manual administration of isatuximab SC at Day 15 of Cycle 6
[Time Frame baseline:6 months from LPI i.e., approximately 16 months]
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).
2.Incidence rate of infusion reactions (IRs)
[Time Frame baseline:18 months after LPI i.e., approximately 28 months]
3.Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and changes in laboratory parameters
[Time Frame baseline: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]
4.Incidence rate of injection site reactions (ISRs)
[Time Frame baseline:18 months after LPI i.e., approximately 28 months]
5.PK concentration: trough plasma concentration (Ctrough)
[Time Frame baseline:Cycle 2 Day 1 and Cycle 6 Day 1 (1 Cycle = 28 days)]
Blood samples will be collected for measurement of isatuximab concentrations.
6.Proportion of participants with sCR, CR, VGPR, and PR according to the 2016 IMWG criteria assessed by IRC
[Time Frame baseline:18 months after LPI i.e., approximately 28 months]
7.Duration of response (DOR)
[Time Frame baseline:18 months after LPI i.e., approximately 28 months]
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.
8.Time to first response (TT1R)
[Time Frame baseline:18 months after LPI i.e., approximately 28 months]
TT1R defined as time from randomization to first IRC determined response (PR or better) that is subsequently confirmed.
9.Time to best response (TTBR)
[Time Frame baseline:18 months after LPI i.e., approximately 28 months]
TTBR defined as time from randomization to first occurrence of IRC determined best response (PR or better) that is subsequently confirmed.
10.Progression free survival (PFS)
[Time Frame baseline:18 months after LPI i.e., approximately 28 months]
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.
11.Overall survival (OS)
[Time Frame baseline:18 months after LPI i.e., approximately 28 months]
OS defined as time from the date of randomization to death from any cause
12.Incidence of participants with anti-drug antibodies (ADA) against isatuximab
[Time Frame baseline:From Cycle 1 Day 1 to follow-up (90 days from last administration) i.e., approximately 13 months (1 Cycle = 28 days)]
13.Patient Expectations Questionnaire at Baseline (PEQ-BL v2) with isatuximab administered subcutaneously
[Time Frame baseline:Baseline]
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).
14.Patient experience and satisfaction questionnaires (PESQ v2) with isatuximab administered subcutaneously
[Time Frame baseline:18 months after LPI i.e., approximately 28 months]
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.
15.Health state utility assessed using Health Resource Utilization and Productivity Questionnaire (HRUPQ)
[Time Frame baseline:18 months after LPI i.e., approximately 28 months]
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.
16.Health Related Quality of Life (HRQL)
[Time Frame baseline:18 months after LPI i.e., approximately 28 months]
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.
17.European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)
[Time Frame baseline:18 months after LPI i.e., approximately 28 months]
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.
Sanofi K.K.
National Cancer Center Hospital Institutional Review Board
5-1-1 Tsukiji, Chuo-ku, Tokyo
+81-3-3542-2511
chiken_CT@ml.res.ncc.go.jp
Approval
Feb. 08, 2023
Yes
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
