This study is a multi-center, open-label, non-randomised, single-arm phaseⅠclinical trial to explore the safety and efficacy of FL-33 CAR T therapy for refractory/relapsed acute myeloid leukaemia. The primary endpoints are incidence and type of dose limiting toxicity within 21 days of CAR T infusion; total number, incidence and severity of adverse events (AE) 30 days after CAR T infusion. The secondary endpoints are total number, incidence and severity of AEs 30 days to 2 years after CAR T infusion; objective response rate (ORR), complete response rate (CR) and complete response with incomplete haematological recovery (CRi) by dose group at 15, 30 and 90 Days after CAR T Infusion; duration of response (DOR), progression-free survival (PFS), overall survival (OS); pharmacokinetic characteristics. The trial will use BOIN12 design to explore the optimal biological dose (OBD) of FL-33 CAR T cells for refractory/relapsed acute myeloid leukaemia. FL-33 CAR T is set at two dose levels: 5\*10\^5 (±20%) CAR-T cells/kg for dose 1 (DL-1) and 1\*10\^6 (±20%) CAR-T cells/kg for dose 2 (DL-2), and after the optimal biological dose (OBD) is determined in the dose exploration phase, the dose expansion phase will expand the trial by 6-12 cases at the OBD, enrolling up to 21-27 cases. Enrolment of more than 21 cases can be reported for analysis and the trial will be stopped when enrolment reaches 27 cases.Additionally, an independent observation group was established, comprising two sequential cohorts: a minimum of 3 subjects were enrolled starting from the lowest dose level (DL-1).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
27
Autologous FL-33 CAR T cells are infused intravenously.
Prior-HSCT donor-derived FL-33 CAR T cells are infused intravenously.
Newly matched donor-derived FL-33 CAR T cells are infused intravenously
Optimized FL-33-03 CAR-T cells
Zhaxin Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai
Shanghai, Shanghai Municipality, China
NOT_YET_RECRUITINGShanghai Liquan Hospital
Shanghai, Shanghai Municipality, China
NOT_YET_RECRUITINGThe General Hospital of Western Theater Command PLA
Chengdu, Sichuan, China
NOT_YET_RECRUITINGBeijingGoBroadH
Beijing, China
RECRUITINGDose-limiting toxicity(DLT)
Incidence and type of dose-limiting toxicity(DLT) within 21 days of FL-33 CAR T infusion.
Time frame: 21 days
Adverse events (AEs)
Total number, incidence and severity of adverse events (AEs) within 30 days of FL-33 CAR T infusion.
Time frame: 30 days
Long-term Adverse events (AEs)
Total number, incidence and severity of AEs from 30 days to 2 years after FL-33 CAR T infusion will be recorded.
Time frame: From 30 days after FL-33 CAR T infusion to 2 years
Objective Response Rate (ORR)
The assessment of ORR by dose group at 15, 30 and 90 Days after FL-33 CAR T infusion according to National Comprehensive Cancer Network (NCCN) Guidelines Version 1.2024 of Acute myeloid Leukemia.
Time frame: 15, 30, 90 days
Duration of response (DOR)
DOR is defined as the date when CR or CRi response criteria are first met to the date of relapse or death caused by AML in the absence of documented relapse.
Time frame: Up to 2 years
Progression-free survival (PFS)
PFS is defined as the earliest date of occurrence from the first infusion of FL-33 CAR T cells back into the patient who achieved ORR to the earliest date of death from any cause after relapse or remission.
Time frame: Up to 2 years
Overall survival (OS)
OS is defined as the time from FL-33 CAR T infusion to death due to any cause.
Time frame: Up to 2 years
The persistence of FL-33 CAR T cells
The persistence of FL-33 CAR T cells in cerebral spinal fluid (CSF) and peripheral blood (PB) will be measured by flowcytometry and quantitative polymerase chain reaction (qPCR).
Time frame: Up to 2 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.