This is a single center, single arm, open-label, dose escalation, phase 1 study to evaluate the safety, tolerability, preliminary efficacy and immunogenicity of OriV508 injection for patients with relapsed/refractory hematological malignancies.
This investigator-initiated clinical study aims to evaluate OriV506 injection, the self-inactivating lentiviral vector that carries a BCMA/CD19 dual-target CAR, in patients with relapsed refractory B-cell hematological malignancies. The study employs a dose-escalation design to assess safety, tolerability, and preliminary efficacy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
OriV508 injection is one kind of non-replicative self-inactivating lentivirus vector which carries an effective BCMA/CD19 dual-target CAR. OriV508 can be administered intravenously and produce BCMA/CD19 CAR-T in vivo.
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGDose-limiting toxicities (DLTs)
Time frame: Dose-limiting toxicities (DLTs) are evaluated between the infusion and 28 days post-infusion.
Cytokine release syndrome (CRS)
Cytokine release syndrome (CRS) would be graded according to the ASTCT consensus.
Time frame: up to Day 28 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: From the enrollment to up to the end of treatment at 96 weeks after treatment of OriV508 or withdrawal from the study
Overall response rate (ORR)
Clinical efficacy of MM cohort can be evaluated according to the 2016 International Myeloma Working Group consensus criteria. ORR = stringent complete response (sCR) rate + complete response (CR) rate + very good partial response (VGPR) rate + partial response (PR) rate. Clinical efficacy of B-NHL cohort can be evaluated according to the Lugano 2014 criteria. ORR = CR+PR.
Time frame: From OriV508 infusion to the end of treatment at 96 weeks
Complete response (CR) rate
Clinical efficacy of MM cohort can be evaluated according to the 2016 International Myeloma Working Group consensus criteria.Clinical efficacy of B-NHL cohort can be evaluated according to the Lugano 2014 criteria.
Time frame: From OriV508 infusion to the end of treatment at 96 weeks
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.
Time frame: From OriV508 infusion to the end of the treatment at 96 weeks
Time to response (TTR)
TTR is defined as the interval between the initiation of OriV508 treatment and the first assessment of sCR, CR, VGPR or PR.
Time frame: From OriV508 infusion to the end of treatment at 96 weeks
Progression-free survival (PFS)
PFS is defined as the interval between a subject's receipt of OriV508 infusion and the first assessment of disease progression or death.
Time frame: From OriV508 infusion to the end of the treatment at 96 weeks
Overall survival (OS)
OS is defined as the interval between a subject's receipt of OriV508 infusion and death from any cause.
Time frame: From OriV508 infusion to the end of treatment at 96 weeks
Minimal residual disease (MRD) - negative assessment
This outcome is primarily chosen for patients with multiple myeloma and aims to calculate the proportion of all patients achieving MRD negative status.
Time frame: From OriV508 infusion to the end of treatment at 96 weeks
CAR-T kinetics
CAR-T kinetics would be detected by flow cytometry and droplet digital or quantitative polymerase chain reaction 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 4, Day 7, Day 10, Day 14, Day 21, Day 28, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, Week 96 or withdrawal from the study
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