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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
64
Pharmaceutical form:Solution for SC-OBDS administration-Route of administration:SC-OBDS
Pharmaceutical form:As per local commercial product-Route of administration:Oral
Pharmaceutical form:As per local commercial product-Route of administration:Oral or IV
Overall response rate (ORR)
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.
Time frame: 6 months after the Last Participant In (LPI) i.e., approximately 32 months
Number of participants with infusion reactions (IRs)
Time frame: 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)
Time frame: 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)
Time frame: 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
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.
Time frame: 12 months after the Last Participant In (LPI) i.e., approximately 38 months
VGPR or better
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CONTACT
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Pharmaceutical form:As per local commercial product-Route of administration:Oral or IV
Pharmaceutical form:As per local commercial product-Route of administration:Oral (as premedication) or IV/oral equivalent (for management of infusion reaction)
Pharmaceutical form:As per local commercial product-Route of administration:IV
Pharmaceutical form:As per local commercial product-Route of administration:IV
Mayo Clinic in Arizona - Phoenix- Site Number : 8400058
Phoenix, Arizona, United States
RECRUITINGLos Angeles Hematology Oncology Medical Group- Site Number : 8400027
Los Angeles, California, United States
RECRUITINGPrivate Practice - Dr. James R. Berenson- Site Number : 8400044
West Hollywood, California, United States
RECRUITINGSmilow Cancer Center at Yale-New Haven- Site Number : 8400020
New Haven, Connecticut, United States
RECRUITINGMaryland Oncology Hematology- Site Number : 8400038
Washington D.C., District of Columbia, United States
RECRUITINGLife Clinical Trials - Coral Springs- Site Number : 8400055
Coral Springs, Florida, United States
RECRUITINGCenter for Rheumatology, Immunology and Arthritis- Site Number : 8400031
Fort Lauderdale, Florida, United States
RECRUITINGMayo Clinic in Florida- Site Number : 8400002
Jacksonville, Florida, United States
RECRUITINGThe Oncology Institute of Hope & Innovation - Lakeland- Site Number : 8400054
Lakeland, Florida, United States
RECRUITINGD&H Pompano Research Center- Site Number : 8400049
Margate, Florida, United States
RECRUITING...and 24 more locations
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.
Time frame: 12 months after the Last Participant In (LPI) i.e., approximately 38 months
Duration of response (DOR)
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 frame: 12 months after the Last Participant In (LPI) i.e., approximately 38 months
Time to first response (TT1R)
TT1R, defined as the time from first isatuximab administration to first investigator-determined response (PR or better) that is subsequently confirmed.
Time frame: 12 months after the Last Participant In (LPI) i.e., approximately 38 months
Time to best response (TTBR)
TTBR, defined as the time from first isatuximab administration to first occurrence of investigator-determined best response (PR or better) that is subsequently confirmed.
Time frame: 12 months after the Last Participant In (LPI) i.e., approximately 38 months
Patient experience and Satisfaction Questionnaire v2 (PESQ v2)
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.
Time frame: Cycle 3/Day 15 and Cycle 6/Day 15
Positivity titer of anti-drug antibodies (ADA) in a subset of approximately 30 participants
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.
Time frame: From Cycle 1 Day 1 to follow-up (90 days from last administration) i.e, approximately up to 15 months (1 cycle = 28 days)
Maximum observed concentration (Cmax) of isatuximab in a subset of approximately 30 participants
Time frame: 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
Time frame: Multiple timepoints in Cycle 1 (1 cycle = 28 days)