Clinical trial NCT05704049: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Relapsed/Refractory Multiple Myeloma
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2023-01-30
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 methods 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.

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.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: 6 months after the Last Participant In (LPI) i.e., approximately 16 months
Secondary outcomes:
measure: Proportion of participants preferring OBDS over manual administration of isatuximab SC at Day 15 of Cycle 6
timeFrame: 6 months from LPI i.e., approximately 16 months
measure: Incidence rate of infusion reactions (IRs)
timeFrame: 18 months after LPI i.e., approximately 28 months
measure: Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and changes in laboratory parameters
timeFrame: 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
measure: Incidence rate of injection site reactions (ISRs)
timeFrame: 18 months after LPI i.e., approximately 28 months
measure: PK concentration: trough plasma concentration (Ctrough)
timeFrame: Cycle 2 Day 1 and Cycle 6 Day 1 (1 Cycle = 28 days)
measure: Proportion of participants with sCR, CR, VGPR, and PR according to the 2016 IMWG criteria assessed by IRC
timeFrame: 18 months after LPI i.e., approximately 28 months
measure: Duration of response (DOR)
timeFrame: 18 months after LPI i.e., approximately 28 months
measure: Time to first response (TT1R)
timeFrame: 18 months after LPI i.e., approximately 28 months
measure: Time to best response (TTBR)
timeFrame: 18 months after LPI i.e., approximately 28 months
measure: Progression free survival (PFS)
timeFrame: 18 months after LPI i.e., approximately 28 months
measure: Overall survival (OS)
timeFrame: 18 months after LPI i.e., approximately 28 months
measure: Incidence of participants with anti-drug antibodies (ADA) against isatuximab
timeFrame: From Cycle 1 Day 1 to follow-up (90 days from last administration) i.e., approximately 13 months (1 Cycle = 28 days)
measure: Patient Expectations Questionnaire at Baseline (PEQ-BL v2) with isatuximab administered subcutaneously
timeFrame: Baseline
measure: Patient experience and satisfaction questionnaires (PESQ v2) with isatuximab administered subcutaneously
timeFrame: 18 months after LPI i.e., approximately 28 months
measure: Health state utility assessed using Health Resource Utilization and Productivity Questionnaire (HRUPQ)
timeFrame: 18 months after LPI i.e., approximately 28 months
measure: Health Related Quality of Life (HRQL)
timeFrame: 18 months after LPI i.e., approximately 28 months
measure: European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)
timeFrame: 18 months after LPI i.e., approximately 28 months
Other outcomes:
Locations:
city: Wollongong
country: Australia
facility: Investigational Site Number : 0360002
state: New South Wales
city: Fitzroy
country: Australia
facility: Investigational Site Number : 0360001
state: Victoria
city: Porto Alegre
country: Brazil
facility: Hospital Mae de Deus Site Number : 0760002
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Clínica São Germano Site Number : 0760003
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas de Sao Paulo Site Number : 0760001
state: São Paulo
city: Brno
country: Czechia
facility: Investigational Site Number : 2030002
city: Olomouc
country: Czechia
facility: Investigational Site Number : 2030004
city: Ostrava - Poruba
country: Czechia
facility: Investigational Site Number : 2030003
city: Praha 2
country: Czechia
facility: Investigational Site Number : 2030001
city: Athens
country: Greece
facility: Investigational Site Number : 3000001
city: Athens
country: Greece
facility: Investigational Site Number : 3000002
city: Thessaloniki
country: Greece
facility: Investigational Site Number : 3000003
city: Kashiwa-shi
country: Japan
facility: Investigational Site Number : 3920001
state: Chiba
city: Okayama-shi
country: Japan
facility: Investigational Site Number : 3920002
state: Okayama
city: Braga
country: Portugal
facility: Investigational Site Number : 6200001
city: Lisboa
country: Portugal
facility: Investigational Site Number : 6200004
city: Lisboa
country: Portugal
facility: Investigational Site Number : 6200005
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: