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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05704049




Registration number
NCT05704049
Ethics application status
Date submitted
20/01/2023
Date registered
30/01/2023

Titles & IDs
Public title
A Study to Investigate Subcutaneous Isatuximab in Combination With Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma
Scientific 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)
Secondary ID [1] 0 0
U1111-1280-5090
Secondary ID [2] 0 0
ACT17453
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed/Refractory Multiple 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
Treatment: Drugs - Carfilzomib
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Dexamethasone IV
Treatment: Drugs - Montelukast
Treatment: Drugs - Acetaminophen
Treatment: Drugs - Diphenhydramine
Treatment: Drugs - Methylprednisolone

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.

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.

Experimental: Part 2 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.

Experimental: Part 2 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.


Treatment: Drugs: Isatuximab
Investigational medicinal product; Pharmaceutical form: Solution for Subcutaneous administration; Route of administration: Subcutaneous

Treatment: Drugs: Carfilzomib
Investigational medicinal product; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous

Treatment: Drugs: Dexamethasone
Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Tablet; Route of administration: Oral

Treatment: Drugs: Dexamethasone IV
Investigational medicinal product/background treatment; ATC code: H02AB02; Pharmaceutical form: Powder for solution for infusion; Route of administration: Intravenous

Treatment: Drugs: Montelukast
Background Treatment; ATC code: R03DC03; Pharmaceutical form: As per local commercial product; Route of administration: Oral

Treatment: Drugs: Acetaminophen
Background Treatment; ATC code: N02BE01; Pharmaceutical form: As per local commercial product; Route of administration: Oral or intravenous (IV)

Treatment: Drugs: Diphenhydramine
Background Treatment; ATC code: R06AA02; Pharmaceutical form: As per local commercial product; Route of administration: Oral or IV

Treatment: Drugs: Methylprednisolone
Background Treatment/Rescue medication; ATC code: H02AB04; Pharmaceutical form: As per local commercial product; Route of administration: IV

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall response rate (ORR)
Timepoint [1] 0 0
6 months after the Last Participant In (LPI) i.e., approximately 16 months
Secondary outcome [1] 0 0
Proportion of participants preferring OBDS over manual administration of isatuximab SC at Day 15 of Cycle 6
Timepoint [1] 0 0
6 months from LPI i.e., approximately 16 months
Secondary outcome [2] 0 0
Incidence rate of infusion reactions (IRs)
Timepoint [2] 0 0
18 months after LPI i.e., approximately 28 months
Secondary outcome [3] 0 0
Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and changes in laboratory parameters
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Incidence rate of injection site reactions (ISRs)
Timepoint [4] 0 0
18 months after LPI i.e., approximately 28 months
Secondary outcome [5] 0 0
PK concentration: trough plasma concentration (Ctrough)
Timepoint [5] 0 0
Cycle 2 Day 1 and Cycle 6 Day 1 (1 Cycle = 28 days)
Secondary outcome [6] 0 0
Proportion of participants with sCR, CR, VGPR, and PR according to the 2016 IMWG criteria assessed by IRC
Timepoint [6] 0 0
18 months after LPI i.e., approximately 28 months
Secondary outcome [7] 0 0
Duration of response (DOR)
Timepoint [7] 0 0
18 months after LPI i.e., approximately 28 months
Secondary outcome [8] 0 0
Time to first response (TT1R)
Timepoint [8] 0 0
18 months after LPI i.e., approximately 28 months
Secondary outcome [9] 0 0
Time to best response (TTBR)
Timepoint [9] 0 0
18 months after LPI i.e., approximately 28 months
Secondary outcome [10] 0 0
Progression free survival (PFS)
Timepoint [10] 0 0
18 months after LPI i.e., approximately 28 months
Secondary outcome [11] 0 0
Overall survival (OS)
Timepoint [11] 0 0
18 months after LPI i.e., approximately 28 months
Secondary outcome [12] 0 0
Incidence of participants with anti-drug antibodies (ADA) against isatuximab
Timepoint [12] 0 0
From Cycle 1 Day 1 to follow-up (90 days from last administration) i.e., approximately 13 months (1 Cycle = 28 days)
Secondary outcome [13] 0 0
Patient Expectations Questionnaire at Baseline (PEQ-BL v2) with isatuximab administered subcutaneously
Timepoint [13] 0 0
Baseline
Secondary outcome [14] 0 0
Patient experience and satisfaction questionnaires (PESQ v2) with isatuximab administered subcutaneously
Timepoint [14] 0 0
18 months after LPI i.e., approximately 28 months
Secondary outcome [15] 0 0
Health state utility assessed using Health Resource Utilization and Productivity Questionnaire (HRUPQ)
Timepoint [15] 0 0
18 months after LPI i.e., approximately 28 months
Secondary outcome [16] 0 0
Health Related Quality of Life (HRQL)
Timepoint [16] 0 0
18 months after LPI i.e., approximately 28 months
Secondary outcome [17] 0 0
European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)
Timepoint [17] 0 0
18 months after LPI i.e., approximately 28 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 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 2
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)
NSW,VIC
Recruitment hospital [1] 0 0
Investigational Site Number : 0360002 - Wollongong
Recruitment hospital [2] 0 0
Investigational Site Number : 0360001 - Fitzroy
Recruitment postcode(s) [1] 0 0
2500 - Wollongong
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment outside Australia
Country [1] 0 0
Brazil
State/province [1] 0 0
Rio Grande Do Sul
Country [2] 0 0
Brazil
State/province [2] 0 0
São Paulo
Country [3] 0 0
Czechia
State/province [3] 0 0
Brno
Country [4] 0 0
Czechia
State/province [4] 0 0
Olomouc
Country [5] 0 0
Czechia
State/province [5] 0 0
Ostrava - Poruba
Country [6] 0 0
Czechia
State/province [6] 0 0
Praha 2
Country [7] 0 0
Greece
State/province [7] 0 0
Athens
Country [8] 0 0
Greece
State/province [8] 0 0
Thessaloniki
Country [9] 0 0
Japan
State/province [9] 0 0
Chiba
Country [10] 0 0
Japan
State/province [10] 0 0
Okayama
Country [11] 0 0
Portugal
State/province [11] 0 0
Braga
Country [12] 0 0
Portugal
State/province [12] 0 0
Lisboa

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.