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

Sanofi

Status and phase

Active, not recruiting

Phase 2

Conditions

Relapsed/Refractory Multiple Myeloma

Treatments

Drug: Dexamethasone IV

Drug: Isatuximab

Drug: Acetaminophen

Drug: Dexamethasone

Drug: Diphenhydramine

Drug: Montelukast

Drug: Methylprednisolone

Drug: Carfilzomib

Study type

Interventional

Funder types

Industry

Identifiers

NCT05704049

2023-508870-27 (Registry Identifier)

ACT17453

U1111-1280-5090 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

74 patients

Sex

All

Ages

18+ years old

Volunteers

No 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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

74 participants in 4 patient groups

Cohort 1: manual administration

Experimental group

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, in combination with carfilzomib and dexamethasone. Participants may receive other treatments as rescue medication or background medication.

Treatment:

Drug: Carfilzomib

Drug: Methylprednisolone

Drug: Montelukast

Drug: Diphenhydramine

Drug: Dexamethasone

Drug: Acetaminophen

Drug: Dexamethasone IV

Drug: Isatuximab

Part 1 Cohort 2: manual administration

Experimental group

Description:

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.

Treatment:

Drug: Carfilzomib

Drug: Methylprednisolone

Drug: Montelukast

Drug: Diphenhydramine

Drug: Dexamethasone

Drug: Acetaminophen

Drug: Dexamethasone IV

Drug: Isatuximab

Part 2 Randomized Cohort: OBDS to manual

Experimental group

Description:

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.

Treatment:

Drug: Carfilzomib

Drug: Methylprednisolone

Drug: Montelukast

Drug: Diphenhydramine

Drug: Dexamethasone

Drug: Acetaminophen

Drug: Dexamethasone IV

Drug: Isatuximab

Part 2 Randomized Cohort: Manual to OBDS

Experimental group

Description:

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:

Drug: Carfilzomib

Drug: Methylprednisolone

Drug: Montelukast

Drug: Diphenhydramine

Drug: Dexamethasone

Drug: Acetaminophen

Drug: Dexamethasone IV

Drug: Isatuximab