This is an investigator-initiated (IIS), phase 2, prospective, open-label, multinational study, designed to be conducted in approximately 14 sites. Eligible patients will initially receive six 28-day cycles of isatuximab, pomalidomide, and low-dose dexamethasone. Following this phase: Patients who achieve ≥VGPR will be randomized in a 1:1 ratio to receive isatuximab, given either Q2W or once monthly, plus pomalidomide and low-dose dexamethasone. Patients with \<VGPR will continue treatment with isatuximab Q2W, pomalidomide, and low-dose dexamethasone. The study will last for 42 months (recruitment and follow-up period), starting from the date of the first patient in (FPI) to the date of the last patient last visit (LPLV). Core study procedures consist of baseline and post-baseline safety and disease evaluations, including physical examination, hematologic/clinical chemistry tests, radiologic assessments, bone marrow evaluations, and blood/urine M-protein assessments. Patients will be allowed to continue treatment until disease progression, death, unacceptable AEs, lost to follow-up, or consent withdrawal.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
108
Intravenous (IV) infusion. Dose regimen: Isatuximab will be given at a dose of 10 mg/kg QW by IV infusion on Days 1, 8, 15, and 22 in Cycle 1 and Days 1 and 15 in subsequent cycles. In patients with ≥VGPR who will be randomized to receive isatuximab once monthly from Cycle 7, isatuximab will be given on day 1 of each cycle.
Route of administration: Oral (PO). Dose regimen: Pomalidomide will be given at 4 mg orally (PO) will be given on Days 1-21 of each cycle.
Route of administration: PO or IV. Dose regimen: Dexamethasone will be given at 40 mg (20 mg for ≥75 years old) PO, or IV will be given on days 1, 8, 15, and 22 in each cycle.
Route of administration: PO. Dose regimen: Acetaminophen (paracetamol) will be given at 650-1000 mg PO 15-30 minutes (but no longer than 60 minutes) before isatuximab infusion
Route of administration: IV. Dose regimen: Ranitidine or equivalent will be given at 50 mg 15-30 minutes (but no longer than 60 minutes) before isatuximab infusion.
Route of administration: IV. Dose regimen: Diphenhydramine or equivalent will be given at 25-50 mg 15-30 minutes (but no longer than 60 minutes) before isatuximab infusion.
General Hospital of Athens "Evangelismos"
Athens, Greece
Anticancer Oncology Hospital of Athens "Agios Savvas"
Athens, Greece
General Hospital of Athens "Alexandra"
Athens, Greece
University General Hospital of Ioannina
Ioannina, Greece
University General Hospital of Patra
Pátrai, Greece
Anticancer Hospital of Thessaloniki "Theageneio"
Thessaloniki, Greece
Overall Response Rate (ORR)
The primary endpoint is the ORR after six months of treatment with isatuximab in combination with pomalidomide, and low-dose dexamethasone. ORR is defined as the proportion of patients with stringent complete response (sCR), complete response (CR), VGPR, and partial response (PR), as assessed by the Investigator using the IMWG response criteria.
Time frame: After six months of treatment with isatuximab plus pomalidomide and low-dose dexamethasone
Progression-free Survival
Defined as the time from study treatment initiation (Cycle 1 Day 1) to the date of first documentation of progressive disease (PD), as assessed by the Investigator using the IMWG response criteria, or the date of death from any cause, or the initiation of further anti-myeloma treatment, or data cut-off, whichever occurs first.
Time frame: From study treatment initiation to progressive disease (PD), or initiation of further anti-myeloma treatment, or death, whichever occurs first. Maximum time period 42 months.
Overall Survival (OS)
Defined as the time from study treatment initiation (Cycle 1 Day 1) to the date of death from any cause. OS will be assessed throughout the treatment period and post EOT during long term follow-up until the end of the study.
Time frame: From study treatment initiation to death. Maximum time period 42 months.
Minimal Residual Response (MRD)
Defined as the proportion of patients achieving MRD-negative status, assessed at CR.
Time frame: Through study completion. Maximum time 42 months.
Time to Response (TTR)
Defined as the time from study treatment initiation (Cycle 1, Day 1) to the date of the first objective response of PR or better.
Time frame: From study treatment initiation to partial response (PR), or better. Maximum time period 42 months.
Duration of Response (DoR)
Defined as the time from the date of the first response, as determined by the Investigator, to the date of the first PD (based on the International Myeloma Working Group \[IMWG\] response criteria) or death, whichever occurs first. DoR will be determined only for patients who have achieved ≥PR.
Time frame: From time response is achieved to progressive disease (PD), or death, whichever comes first. Maximum time period 42 months.
Safety
i.e. Adverse Events (AEs), Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs).
Time frame: Study treatment initiation until 30 days after last study treatment. Maximum time period 42 months.
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