This Phase 1, open-label, single-arm, dose-escalation study is designed to evaluate the safety and tolerability of SL1617 Injection in patients with relapsed or refractory B-cell lymphoma. SL1617 is an investigational in vivo CAR T-cell immunotherapy targeting CD19 and CD20, utilizing an engineered lentiviral vector to generate functional CAR-T cells in vivo without the need for ex vivo cell processing or lymphodepletion. Participants will receive a single intravenous infusion of SL1617 using a traditional 3+3 dose-escalation design. The planned starting dose is 1.0 × 10\^9 transducing units (TU), followed by dose levels of 3.0 × 10\^9 TU and 6.0 × 10\^9 TU. Dose escalation will be guided by the occurrence of dose-limiting toxicities (DLTs).
This Phase 1, open-label, single-arm, dose-escalation study is designed to evaluate the safety and tolerability of SL1617 Injection in patients with relapsed or refractory B-cell lymphoma. SL1617 Injection is an investigational in vivo CAR T-cell immunotherapy targeting CD19 and CD20, based on an engineered lentiviral vector system. The vector is designed to specifically target and transduce T cells and NK cells in vivo, enabling in situ generation of functional CAR-expressing immune cells following a single intravenous infusion SL1617 Injection will be administered as a single intravenous infusion. Dose escalation will follow a traditional 3+3 design. The planned starting dose is 1.0 × 10\^9 transducing units (TU), followed sequentially by dose levels of 3.0 × 10\^9 TU and 6.0 × 10\^9 TU. At each dose level, three participants will initially be enrolled. If none of the first three participants experiences a dose-limiting toxicity (DLT), enrollment may proceed to the next dose level. If two or more of the first three participants experience a DLT, further dose escalation will be stopped. If one of the first three participants experiences a DLT, three additional participants will be enrolled at the same dose level. Dose escalation may proceed if none of the three additional participants experiences a DLT. Dose escalation will be stopped if at least one of the three additional participants experiences a DLT, resulting in DLTs in at least two of six participants at that dose level. If the maximum tolerated dose (MTD) is not reached after completion of the DLT observation period for the 6.0 × 10\^9 TU dose cohort, the investigators may explore higher dose levels based on cumulative safety data and pharmacodynamic evidence. The primary objective is to evaluate the safety of SL1617 Injection, including the incidence and severity of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, hematologic toxicity, organ toxicity, and other treatment-related adverse events. Secondary objectives include assessment of preliminary antitumor activity using objective response rate, complete response rate, partial response rate, overall survival, progression-free survival, and event-free survival. Exploratory objectives include characterization of in vivo CAR-T cell kinetics (CAR copy number, Cmax, Tmax, and AUC28d) and clonal evolution.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Participants with relapsed or refractory B-cell lymphoma will receive SL1617 Injection, an investigational in vivo CD19/CD20-targeted CAR T-cell immunotherapy, by intravenous infusion according to the protocol. Participants will subsequently undergo safety and efficacy assessments for up to 24 months after treatment.
Chinese PLA General Hospital, Beijing, Beijing 100853
Beijing, China
RECRUITINGIncidence and Severity of Adverse Events
The number, percentage, and severity of adverse events (AEs) following SL1617 Injection infusion, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematologic toxicity, organ toxicity, and other immune therapy-related toxicities, graded per CTCAE v6.0.
Time frame: From SL1617 infusion through 24 months after treatment
Incidence of Dose-Limiting Toxicities (DLTs)
The number and percentage of participants who experience DLTs during the protocol-defined DLT observation period (Days 1-28) following a single intravenous infusion of SL1617 Injection.
Time frame: During the protocol-defined DLT observation period after SL1617 infusion
Objective Response Rate at Prespecified Follow-up Time Points
The objective response rate (ORR) at 1, 3, 6, 9, 12, 18, and 24 months after treatment, defined as the proportion of participants who achieve a complete response (CR) or partial response (PR).
Time frame: At 1, 3, 6, 9, 12, 18, and 24 months after SL1617 infusion
Complete Response Rate
The proportion of participants who achieve a complete response at each prespecified assessment time point.
Time frame: At 1, 3, 6, 9, 12, 18, and 24 months after SL1617 infusion
Partial Response Rate
The proportion of participants who achieve a partial response at each prespecified assessment time point.
Time frame: At 1, 3, 6, 9, 12, 18, and 24 months after SL1617 infusion
Overall Survival
Overall survival (OS), defined as the time from SL1617 infusion to death from any cause. Participants who are alive at the last follow-up will be censored on the date of their last known survival status.
Time frame: From SL1617 infusion through 24 months after treatment
Progression-Free Survival
Progression-free survival (PFS), defined as the time from SL1617 infusion to the first documented disease progression or death from any cause, whichever occurs first. Participants without an event will be censored at the date of their last disease assessment.
Time frame: From SL1617 infusion through 24 months after treatment
Event-Free Survival
Event-free survival (EFS), defined as the time from SL1617 infusion to the occurrence of a protocol-defined event, including disease progression, relapse, initiation of new anti-lymphoma therapy, or death from any cause, whichever occurs first. Participants without an event will be censored at the date of their last follow-up.
Time frame: From SL1617 infusion through 24 months after treatment
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