CLL-1-Targeted In Vivo CAR-T Cell Immunotherapy for Relapsed/Refractory Acute Myeloid Leukemia
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorLiping Dou
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Voluntarily agrees to participate in the study, has signed the informed consent form, and is willing and able to comply with scheduled visits, study treatment, laboratory tests, and other study procedures.
Relapsed AML: Reappearance of leukemic cells in the peripheral blood after achieving complete remission (CR), bone marrow blasts ≥5% (excluding bone marrow regeneration after consolidation chemotherapy or other non-leukemic causes), or the presence of extramedullary leukemic infiltration.
Refractory AML: Newly diagnosed AML with no response after two courses of standard induction therapy; relapse within 12 months after achieving CR followed by consolidation/intensification therapy; relapse more than 12 months after CR with failure to respond to conventional chemotherapy; two or more relapses; or persistent extramedullary leukemia.
CLL-1 expression ≥50% on AML blasts, confirmed by flow cytometry on bone marrow or peripheral blood samples at the local certified laboratory.
Disqualifiers
The patient has severe cardiac dysfunction, or left ventricular ejection fraction (LVEF) <50%, or a history within the 12 months prior to enrollment of myocardial infarction, coronary angioplasty or coronary stent implantation, unstable angina, clinically significant arrhythmia, or other severe cardiovascular diseases.
A history of severe pulmonary disease associated with impaired lung function.
Concurrent progressive malignancy other than acute myeloid leukemia.
Severe active infection that cannot be effectively controlled.
Trial design
Design model
Single group
Treatments tested in this trial
SL1CC Injection
DrugSL1CC 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).
Treatment groups
12 Participants
are divided into 1 treatment groupGroup A: SL1CC Treatment GroupExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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 months2
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)Secondary outcomes
1
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 infusion2
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 infusion3
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 infusion4
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 treatmentSponsors and contacts
Click on the lead sponsor to view all of their trials.
Liping Dou
Lead sponsor
Chinese PLA General Hospital
Sponsor institution
Hebei Senlang Biotechnology Inc., Ltd.
Collaborator
Source ClinicalTrials.gov
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