This is a single center, single arm, open-label, dose escalation, phase 1 study to evaluate the safety, tolerability, preliminary efficacy and immunogenicity of ESO-T01 for patients with relapsed/refractory multiple myeloma.
This investigator-initiated clinical study aims to evaluate ESO-T01, the third-generation self-inactivating lentiviral vector that carries a BCMA-targeted CAR, in patients with relapsed refractory multiple myeloma (MM). The study employs a dose-escalation design to assess safety, tolerability, and preliminary efficacy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
ESO-T01 Injection is one kind of third-generation non-replicative self-inactivating lentivirus vector which carries an effective BCMA-targeted CAR. ESO-T01 can be administered intravenously and produce CAR-T in vivo.
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
Cytokine release syndrome (CRS)
Cytokine release syndrome (CRS) would be graded according to the ASTCT consensus.
Time frame: up to Day 28 post-infusion
Dose-limiting toxicities (DLTs)
Time frame: Dose-limiting toxicities (DLTs) are evaluated between the infusion and 28 days post-infusion.
immune cell-associated immune effector cell-associated neurotoxicity syndrome (ICANS)
ICANS would be scored according to Immune Effector Cell-Associated Encephalopathy (ICE), and then graded by the ASTCT consensus.
Time frame: up to Day 28 post-infusion
Treatment-associated adverse effects (AEs)
All other AEs would be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
Time frame: up to 2 years after treatment of ESO-T01
Overall response rate (ORR)
Clinical efficacy can be evaluated according to the 2016 International Myeloma Working Group consensus criteria.
Time frame: Day 14, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of ESO-T01.
Complete response (CR) rate
sCR/CR can be evaluated according to the 2016 International Myeloma Working Group consensus criteria.
Time frame: Day 14, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of ESO-T01.
Duration of response (DOR)
DOR is defined as the interval between the first sCR, CR, VGPR, or PR after infusion and the disease progression or death.
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Time frame: Through study completion, an average of 2 year
Progression-free survival (PFS)
PFS is defined as the interval between a subject's receipt of ESO-T01 infusion and the first assessment of disease progression or death.
Time frame: up to 2 years after treatment of ESO-T01.
Overall survival (OS)
OS is defined as the interval between a subject's receipt of ESO-T01 infusion and death from any cause.
Time frame: up to 2 years after treatment of ESO-T01
Cmax
CAR-T kinetics would be detected by flow cytometry and droplet digital PCR in peripheral blood and bone marrow at each important time points. Cmax is the peak expansion value of CAR-T cells.
Time frame: Baseline, Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 14, Day 17, Day 21, Day 24, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of ESO-T01
Tmax
CAR-T kinetics would be detected by flow cytometry and droplet digital PCR in peripheral blood and bone marrow at each important time points. Tmax is the time of the occurrence of expansion peak.
Time frame: Baseline, Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 14, Day 17, Day 21, Day 24, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment of ESO-T01
AUC(0-day 28)
CAR-T kinetics would be detected by flow cytometry and droplet digital PCR in peripheral blood and bone marrow at each important time points. Cmax is the peak expansion value of CAR-T cells. AUC(0- day28) refers to the area under curve of CAR-T cell expansion between infusion and day 28 post infusion. They all reflect the pharmacokinetics.
Time frame: Baseline, Day 2, Day 4, Day 6, Day 8, Day 10, Day 12, Day 14, Day 17, Day 21, Day 24, Day 28 after the treatment of ESO-T01