Plasma Cell Myeloma Refractory
Conditions
Keywords
Anti CD38 monoclonal antibody, SARCLISA
Brief summary
The primary purpose of this study is to assess the efficacy (overall response rate) of subcutaneous (SC) via on body delivery system (SC-OBDS) isatuximab in combination with weekly carfilzomib and dexamethasone (Kd) in adult participants with RRMM having received 1 to 3 prior lines of therapy.
Detailed description
The duration of the study for a participant will include a period for screening of up to 28 days, a study treatment period of 12 months (except early discontinuation), the end-of-treatment (EOT) visit about 30 days after the last dose of study treatment, and a study follow-up period until death or the final study cut-off date. A cycle duration is 28 days. After study treatment discontinuation, participants will return to the study site 30 days after the last dose of study treatment for the EOT visit or before further anti-myeloma therapy initiation, whichever comes first.
Interventions
DRUGDiphenhydramine
Pharmaceutical form:As per local commercial product-Route of administration:Oral (as premedication) or IV/oral equivalent (for management of infusion reaction)
Pharmaceutical form:Solution for SC-OBDS administration-Route of administration:SC-OBDS
DRUGMontelukast
Pharmaceutical form:As per local commercial product-Route of administration:Oral
DRUGDexamethasone
Pharmaceutical form:As per local commercial product-Route of administration:Oral or IV
DRUGAcetaminophen
Pharmaceutical form:As per local commercial product-Route of administration:Oral or IV
DRUGMethylprednisolone
Pharmaceutical form:As per local commercial product-Route of administration:IV
DRUGCarfilzomib
Pharmaceutical form:As per local commercial product-Route of administration:IV
Sponsors
Sanofi
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have a documented diagnosis of 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). * Participants with relapsed and/or refractory MM with at least 1 prior line of therapy and no more than 3 prior lines of therapy. * Contraceptive use by \[men and women\] should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Male participants agree to practice true abstinence or agree to use contraception while receiving study treatment, during dose interruptions and at least 5 months following study treatment discontinuation, even if has undergone a successful vasectomy. * A female participant is eligible to participate if she is not pregnant, not breastfeeding, and either is not a female of childbearing potential (FCBP XE " FCBP " \\f Abbreviation \\t "female of childbearing potential" ) or agrees to practice complete abstinence or use contraception. * Capable of giving signed informed consent.
Exclusion criteria
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 \< 6 months before first isatuximab administration or, b) intolerant to the anti-CD38 previously received. * Participants who are refractory to 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. * Participants with contraindication to dexamethasone and/or to carfilzomib. * Any anti-myeloma drug treatment within 14 days before the first isatuximab administration, including dexamethasone. * Prior allogenic HSC transplant with active graft versus host disease (GvHD XE " GvHD " \\f Abbreviation \\t "graft versus host disease" ) (GvHD any grade and/or being under immunosuppressive treatment within the last 2 months). * Any major procedure within 14 days before the first isatuximab administration: plasmapheresis, major surgery (kyphoplasty is not considered a major procedure), radiotherapy. * Vaccination with a live vaccine within 4 weeks before the first isatuximab administration. Seasonal flu vaccines that do not contain live virus are permitted. * Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures. The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | 6 months after the Last Participant In (LPI) i.e., approximately 32 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 IMWG criteria assessed by investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with infusion reactions (IRs) | From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 38 months | — |
| Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and laboratory abnormalities (per NCI-CTCAE grade or PCSA if NCI-CTCAE scale is not applicable) | From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 38 months | — |
| Number of participants with injection site reactions (ISRs) | From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 38 months | — |
| CR or better | 12 months after the Last Participant In (LPI) i.e., approximately 38 months | CR or better assessed according to International Myeloma Working Group (IMWG) criteria assessed by investigator. CR is defined as negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, \<5% plasma cells in bone marrow aspirates, and a normal FLC ratio of 0.26-1.65 is required for FLC disease only. Two consecutive assessments are needed. No known evidence of progressive disease or new bone/soft tissue lesions if radiographic studies were performed. |
| VGPR or better | 12 months after the Last Participant In (LPI) i.e., approximately 38 months | VGPR or better assessed according to IMWG criteria assessed by investigator. VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 h, or ≥90% decrease in the sum of maximal perpendicular diameter compared to baseline in soft tissue plasmacytoma. FLC only: a ≥90% decrease in the difference between involved and uninvolved FLC levels. Two consecutive assessments are needed. No known evidence of progressive disease or new bone/soft tissue lesions if radiographic studies were performed. |
| Duration of response (DOR) | 12 months after the Last Participant In (LPI) i.e., approximately 38 months | DOR, defined as the time from date of first investigator determined response for achieving PR or better to first documentation of progressive disease (PD) determined by investigator or death, whichever occurred first. |
| Time to first response (TT1R) | 12 months after the Last Participant In (LPI) i.e., approximately 38 months | TT1R, defined as the time from first isatuximab administration to first investigator-determined response (PR or better) that is subsequently confirmed. |
| Time to best response (TTBR) | 12 months after the Last Participant In (LPI) i.e., approximately 38 months | TTBR, defined as the time from first isatuximab administration to first occurrence of investigator-determined best response (PR or better) that is subsequently confirmed. |
| Patient experience and Satisfaction Questionnaire v2 (PESQ v2) | Cycle 3/Day 15 and Cycle 6/Day 15 | The PESQ v2 has been designed to follow up on participant experience and satisfaction regarding the treatment (side effects and recommendation) and the administration method (comfortability, pain, side effects and overall satisfaction). 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 trial specific version of the PESQ v2 contains of items administered for the duration of treatment. Response options are presented as a 5-point Likert scale ranging from Strongly agree/very satisfied/definitely yes to strongly disagree/very dissatisfied/definitely no. |
| Positivity titer of anti-drug antibodies (ADA) in a subset of approximately 30 participants | From Cycle 1 Day 1 to follow-up (90 days from last administration) i.e, approximately up to 15 months (1 cycle = 28 days) | Blood samples will be collected for assessing the presence of ADA against isatuximab in plasma from approximately 30 participants. Plasma samples will be screened for antibodies binding to isatuximab and the titer of confirmed positive samples will be reported. |
| Maximum observed concentration (Cmax) of isatuximab in a subset of approximately 30 participants | Multiple timepoints in Cycle 1 (1 cycle = 28 days) | — |
| Cumulative area under the curve over the first 4 weeks of isatuximab treatment (AUC4 weeks) in a subset of approximately 30 participants | Multiple timepoints in Cycle 1 (1 cycle = 28 days) | — |
Countries
United States
Contacts
CONTACTTrial Transparency email recommended (Toll free for US & Canada)
Outcome results
None listed