This is a single-center, open-label, single-arm, phase 1 dose-escalation study to evaluate the safety, tolerability, preliminary efficacy, and cellular kinetics of SL1CC Injection, an in vivo CAR-T therapy targeting CLL-1, in patients with relapsed or refractory acute myeloid leukemia (R/R AML; acute promyelocytic leukemia excluded). SL1CC Injection is administered as a single intravenous infusion without lymphodepleting conditioning. Dose escalation follows a traditional 3+3 design with planned dose levels of 1 × 10\^9, 3 × 10\^9, and 6 × 10\^9 transducing units (TU), guided by the occurrence of dose-limiting toxicities (DLTs). Treatment-emergent adverse events and serious adverse events, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematologic toxicity, organ toxicity, and other immune therapy-related toxicities, will be assessed. Preliminary antitumor activity, assessed by composite complete remission (CR/CRi) and measurable residual disease (MRD) status according to the European LeukemiaNet (ELN) 2022 criteria, and the expansion and persistence of CAR-T cells in peripheral blood will also be evaluated.
This is a single-center, single-arm, open-label, phase 1 dose-escalation study of SL1CC Injection in adults with R/R AML. SL1CC is an in vivo CAR-T product in which a lentiviral vector (LVV) encoding a CLL-1-specific chimeric antigen receptor is administered intravenously to transduce the patient's endogenous T cells in situ; no leukapheresis, ex vivo manufacturing, or lymphodepleting conditioning is required. Three dose levels are planned (1 × 10\^9, 3 × 10\^9, and 6 × 10\^9 TU) using a traditional 3+3 escalation design, and dose-limiting toxicity (DLT) is assessed during the first 28 days after a single infusion. Anticipated enrollment is 12 participants (range 9-18, depending on the number of dose levels requiring expansion). The study includes a screening period, a treatment (infusion) period, and a follow-up period of up to 24 months. Safety assessments include adverse events and serious adverse events graded per NCI CTCAE v6.0, with CRS and ICANS graded per the ASTCT consensus criteria; hematologic recovery, infection, organ toxicity, and viral shedding (blood, saliva, and urine; qPCR) are also monitored. Disease response is assessed by bone marrow morphology according to the ELN 2022 criteria (CR, CRi, MLFS, and PR), together with MRD measured by multiparameter flow cytometry. Exploratory cellular kinetics include peripheral blood CAR transgene copies (qPCR), CAR-positive T-cell counts, Cmax, Tmax, and AUC0-28d. Long-term safety monitoring for potential insertional mutagenesis associated with integrating lentiviral vectors is planned in accordance with applicable gene therapy guidance.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
SL1CC Injection is an investigational in vivo CLL-1-targeted CAR T-cell therapy for patients with relapsed or refractory acute myeloid leukemia. Participants will receive SL1CC Injection by intravenous infusion at protocol-specified dose levels. Dose escalation will follow a traditional 3+3 design and will be guided by the occurrence of dose-limiting toxicities (DLTs).
Chinese PLA General Hospital, Beijing, Beijing 100853
Beijing, China
Incidence and Severity of Adverse Events and Serious Adverse Events
The number, percentage, severity, and relatedness of adverse events (AEs) and serious adverse events (SAEs) occurring from SL1CC infusion through the 12-month safety observation period, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematologic toxicity, organ toxicity, infection, and other immunotherapy-related toxicities. AEs are graded per NCI CTCAE v6.0; CRS and ICANS are graded per the ASTCT consensus criteria.
Time frame: From SL1CC infusion through 12 months after treatment (primary safety observation period); long-term follow-up continues through 24 months
Incidence of Dose-Limiting Toxicities (DLTs)
The number and percentage of participants who experience dose-limiting toxicities (DLTs) during the protocol-defined DLT observation period (Days 0-28) after a single intravenous infusion of SL1CC Injection. DLT definitions are specified in the protocol.
Time frame: From Day 0 through Day 28 after a single SL1CC infusion (protocol-defined DLT observation window)
Objective Response Rate at Prespecified Follow-up Time Points
The objective response rate (ORR) at 1, 2, 3, 6, 9, 12, 18, and 24 months after treatment, defined as the proportion of participants who achieve a complete remission (CR), CR with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), or partial remission (PR), as defined by the European LeukemiaNet (ELN) 2022 recommendations for AML.
Time frame: At 1, 2, 3, 6, 9, 12, 18, and 24 months after SL1CC infusion
Complete Response Rate
The proportion of participants who achieve composite complete remission (CRc; CR + CRi) at each prespecified assessment time point, per the ELN 2022 criteria.
Time frame: At 1, 2, 3, 6, 9, 12, 18, and 24 months after SL1CC infusion
Partial Remission (PR) Rate
The proportion of participants who achieve partial remission (PR) at each prespecified assessment time point, per the ELN 2022 criteria.
Time frame: At 1, 2, 3, 6, 9, 12, 18, and 24 months after SL1CC infusion
Overall Survival
Overall survival (OS), defined as the time from SL1CC 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 SL1CC infusion through 24 months after treatment
Progression-Free Survival
Progression-free survival (PFS), defined as the time from SL1CC infusion to relapse after CR/CRi, disease progression, or death from any cause, whichever occurs first, using the ELN 2022 criteria for relapse and progressive disease. Participants without an event will be censored at the date of the last disease assessment.
Time frame: From SL1CC infusion through 24 months after treatment
Event-Free Survival
Event-free survival (EFS), defined as the time from SL1CC infusion to the occurrence of a protocol-defined event, including failure to achieve CR/CRi at the protocol-defined response assessment, relapse after CR/CRi, initiation of new anti-leukemia therapy, or death from any cause, whichever occurs first, as defined by the ELN 2022 criteria. Participants without an event will be censored at the date of their last follow-up.
Time frame: From SL1CC infusion through 24 months after treatment
Measurable Residual Disease (MRD) Negativity Rate
The proportion of participants with MRD negativity in bone marrow assessed by multiparameter flow cytometry (sensitivity of at least 10\^-4) among participants who achieve CR/CRi, at each prespecified assessment time point.
Time frame: At 1, 2, 3, 6, 9, 12, 18, and 24 months after SL1CC infusion
CAR Transgene Copy Number in Peripheral Blood (qPCR)
CAR transgene copy number in peripheral blood measured by quantitative PCR (qPCR)
Time frame: From Day 0 through 24 months after SL1CC infusion
CAR-Positive T-Cell Counts in Peripheral Blood (Flow Cytometry)
Number of CAR-positive T cells in peripheral blood measured by flow cytometry
Time frame: From Day 0 through 24 months after SL1CC infusion
Peak Expansion of CAR-T Cells (Cmax)
Peak level of CAR transgene expansion in peripheral blood
Time frame: From Day 0 through Day 28 after SL1CC infusion
Time to Peak Expansion (Tmax)
Time from infusion to peak CAR transgene expansion
Time frame: From Day 0 through Day 28 after SL1CC infusion
AUC from Day 0 to Day 28 (AUC0-28d)
Area under the curve of peripheral blood CAR transgene levels from Day 0 to Day 28
Time frame: From Day 0 through Day 28 after SL1CC infusion
Li-Ping Dou, Dr
CONTACT
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