Refractory/Relapsed Acute Myeloid LeukaemiaPhase 1NCT06326021
Optimised CD33 (FL-33) CAR T Therapy for Refractory/Relapsed Acute Myeloid Leukaemia
A Phase 1 study testing autologous FL-33 CAR T therapy, prior-HSCT donor-derived FL-33 CAR T therapy and Newly matched donor-derived FL-33 CAR T therapy in people with Refractory/Relapsed Acute Myeloid Leukaemia, run by Beijing GoBroad Hospital at 4 sites in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 1 year to 70 years
- Conditions the study is for
- Refractory/Relapsed Acute Myeloid Leukaemia
- What is being tested?
- autologous FL-33 CAR T therapy, prior-HSCT donor-derived FL-33 CAR T therapy and Newly matched donor-derived FL-33 CAR T therapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 4 sitesChina
- Study dates
- 2 Apr 2024to 30 Dec 2026
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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;
- Physical condition: 0-2 ECOG score;
- Expected survival ≥ 60 days;
Show all 9Show fewer
- Bone marrow or cerebrospinal fluid tumour cells are positive for CD33 by flow cytometry assay or tumour tissues positive for CD33 by immunohistochemistry (CD33 determination of positivity: flow cytometry: >80% of tumour cells expressing CD33 and MFI similar to normal myeloid cells is considered as full positivity; tumour cells greater than 80% of expression of CD33 but MFI lower than the CD33 expression of normal myeloid cells by 1 log is considered as low expression (dim). Tumour cells with between 20-80% positive CD33 expression are partially expressed; Pathological immunohistochemistry: tumour cells>30% positive are considered to be positively expressed;
- Self-aware patients aged 19-70 years are required to voluntarily sign an informed consent form in writing; paediatric patients aged 1-7 years can be recruited after their legal representative (guardian) had signed an informed consent form; self-aware paediatric patients aged 8-18 years voluntarily sign an informed consent form in writing, and their legal representative (guardian) are required to sign an informed consent form in writing as well;
- Suitable and available allogeneic haematopoietic stem cell transplant donors are required, and allogeneic haematopoietic stem cell transplantation can be performed after receiving FL-33 CAR T treatment.
Who cannot join
- 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;
- Symptoms of severe respiratory failure;
- With other types of malignancy;
Show all 15Show fewer
- Diffuse intravascular coagulation;
- Serum creatinine and/or urea nitrogen ≥ 1.5 times the normal value;
- With sepsis or other uncontrollable infection;
- Suffering from uncontrollable diabetes mellitus;
- Severe mental disorders;
- Have significant intracranial lesions on cranial MRI;
- Organ transplantation (excluding haematopoietic stem cell transplantation) history;
- Female patients (patients of childbearing potential) with positive blood HCG test;
- Hepatitis (including hepatitis B and C) and positive screening for AIDS and syphilis.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China4 sites, 4 recruiting
- Recruiting
BeijingGoBroadH
Beijing
ZeLing Wang, 86+18835570027, wangzl@gobroadhealthcare.com
- Not yet recruiting
The General Hospital of Western Theater Command PLA
Chengdu, Sichuan, 610083
- Not yet recruiting
Zhaxin Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai
Shanghai, Shanghai Municipality, 200435
- Not yet recruiting
Shanghai Liquan Hospital
Shanghai, Shanghai Municipality, 201418
About this study
Official title: Optimised CD33 (FL-33) CAR T Therapy for Refractory/Relapsed Acute Myeloid Leukaemia：a Multi-center, Open-label, Non-randomised, Single-arm Phase Ⅰ Clinical 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).
- Being tested
- autologous FL-33 CAR T therapy, prior-HSCT donor-derived FL-33 CAR T therapy, Newly matched donor-derived FL-33 CAR T therapy, FL33-03 CAR-T therapy
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
autologous FL-33 CAR T therapyDrug
Autologous FL-33 CAR T cells are infused intravenously.
prior-HSCT donor-derived FL-33 CAR T therapyDrug
Prior-HSCT donor-derived FL-33 CAR T cells are infused intravenously.
Newly matched donor-derived FL-33 CAR T therapyDrug
Newly matched donor-derived FL-33 CAR T cells are infused intravenously
FL33-03 CAR-T therapyDrug
Optimized FL-33-03 CAR-T cells
| Study group | Role | What they receive |
|---|---|---|
| Autologous FL-33 CAR T | Experimental | Peripheral blood mononuclear cells for the production of FL-33 CAR T cells are collected from patients. Receives: Drug: autologous FL-33 CAR T therapy |
| Prior-HSCT donor-derived FL-33 CAR T | Experimental | Peripheral blood mononuclear cells for the production of FL-33 CAR T cells are collected from prior-HSCT donors. Receives: Drug: prior-HSCT donor-derived FL-33 CAR T therapy |
| Newly matched donor-derived FL33 CAR T | Experimental | Peripheral blood mononuclear cells for the production of FL-33 CAR T cells are collected from newly matched donors. Receives: Drug: Newly matched donor-derived FL-33 CAR T therapy |
| FL-33-03 CAR T | Experimental | The independent observation group, serving as an exploratory arm, will uniformly enroll at least 3 subjects starting from the lowest dose level (DL-1) into Cohort 1 to evaluate the safety and efficacy of FL33-03 CAR-T (with TNFα inhibitor). If the results from this stage meet expectations, at least 3 additional subjects will be enrolled into Cohort 2 to evaluate the safety and efficacy of FL33-03 CAR-T (without TNFα inhibitor) at the same lowest dose level. Receives: Drug: FL33-03 CAR-T therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity(DLT)
Incidence and type of dose-limiting toxicity(DLT) within 21 days of FL-33 CAR T infusion.
Measured: 21 days
Adverse events (AEs)
Total number, incidence and severity of adverse events (AEs) within 30 days of FL-33 CAR T infusion.
Measured: 30 days
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2024
- Study start2 Apr 2024
- Primary completion15 Jun 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory/Relapsed Acute Myeloid LeukaemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing GoBroad Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- The General Hospital of Western Theater Command, Zhaxin Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, Shanghai Liquan Hospital, Ruijin Hospital
- Responsible party
- Principal investigator, Jing Pan, Beijing GoBroad Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06326021
- Sponsor's protocol ID
- BJGBYY-IIT-LCYJ-2024-004
- Status last verified
- Mar 2026
- First submitted
- 10 Mar 2024
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No