Optimised CD33 (FL-33) CAR T Therapy for Refractory/Relapsed Acute Myeloid Leukaemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age1-70
SponsorBeijing GoBroad Hospital
About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients who met all the inclusion criteria were eligible for enrolment.
Patients diagnosed with primary resistance acute myeloid leukemia, tumour surface antigen CD33 expression, chemotherapy relapse, extramedullary relapse, persistent residual positivity or relapse/refractory after allogeneic haematopoietic stem cell transplantation;
Age 1-70 years old;
No severe allergies;
Disqualifiers
Patients who fulfil any of the following criteria may not be enrolled.
Patients with history of allogeneic HSCT but PBMNC is not available from prior- transplant donor for preparation of CAR T cells and peripheral blood tumour load >30%; patients without history of allogeneic HSCT and peripheral blood tumour load >30%;
Intracranial hypertension or cerebral impaired consciousness;
Symptomatic heart failure or severe arrhythmia;
Trial design
Design model
Parallel
Treatments tested in this trial
autologous FL-33 CAR T therapy
DrugAutologous FL-33 CAR T cells are infused intravenously.
prior-HSCT donor-derived FL-33 CAR T therapy
DrugPrior-HSCT donor-derived FL-33 CAR T cells are infused intravenously.
Newly matched donor-derived FL-33 CAR T therapy
DrugNewly matched donor-derived FL-33 CAR T cells are infused intravenously
FL33-03 CAR-T therapy
DrugOptimized FL-33-03 CAR-T cells
Treatment groups
27 Participants
are divided into 4 treatment groupsGroup A: Autologous FL-33 CAR TExperimental treatment 1 intervention
Group B: Prior-HSCT donor-derived FL-33 CAR TExperimental treatment 1 intervention
Group C: Newly matched donor-derived FL33 CAR TExperimental treatment 1 intervention
Group D: FL-33-03 CAR TExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Dose-limiting toxicity(DLT)
Incidence and type of dose-limiting toxicity(DLT) within 21 days of FL-33 CAR T infusion.
Time frame
21 days2
Adverse events (AEs)
Total number, incidence and severity of adverse events (AEs) within 30 days of FL-33 CAR T infusion.
Time frame
30 daysSecondary outcomes
1
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 years2
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 days3
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 years4
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 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Beijing GoBroad Hospital
Lead sponsor
The General Hospital of Western Theater Command
Collaborator
Zhaxin Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai
Collaborator
Shanghai Liquan Hospital
Collaborator
Ruijin Hospital
Collaborator
Source ClinicalTrials.gov