Optimised CD33 (FL-33) CAR T Therapy for Refractory/Relapsed Acute Myeloid Leukaemia

NCT ID: NCT06326021

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-02
• Study Completion Date: 2026-12-30

Brief 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. 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.

Conditions

Refractory/Relapsed Acute Myeloid Leukaemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Autologous FL-33 CAR T

Peripheral blood mononuclear cells for the production of FL-33 CAR T cells are collected from patients.

Group Type: EXPERIMENTAL

autologous FL-33 CAR T therapy

Intervention Type: DRUG

Autologous FL-33 CAR T cells are infused intravenously.

Prior-HSCT donor-derived FL-33 CAR T

Peripheral blood mononuclear cells for the production of FL-33 CAR T cells are collected from prior-HSCT donors.

Group Type: EXPERIMENTAL

prior-HSCT donor-derived FL-33 CAR T therapy

Intervention Type: DRUG

Prior-HSCT donor-derived FL-33 CAR T cells are infused intravenously.

Newly matched donor-derived FL33 CAR T

Peripheral blood mononuclear cells for the production of FL-33 CAR T cells are collected from newly matched donors.

Group Type: EXPERIMENTAL

Newly matched donor-derived FL-33 CAR T therapy

Intervention Type: DRUG

Newly matched donor-derived FL-33 CAR T cells are infused intravenously

Interventions

autologous FL-33 CAR T therapy

Autologous FL-33 CAR T cells are infused intravenously.

Intervention Type: DRUG

prior-HSCT donor-derived FL-33 CAR T therapy

Prior-HSCT donor-derived FL-33 CAR T cells are infused intravenously.

Intervention Type: DRUG

Newly matched donor-derived FL-33 CAR T therapy

Newly matched donor-derived FL-33 CAR T cells are infused intravenously

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. 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;

2. Age 1-70 years old;

3. No severe allergies;

4. Physical condition: 0-2 ECOG score;

5. Expected survival ≥ 60 days;

6. 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;

7. 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;

8. 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.

Exclusion Criteria

• Patients who fulfil any of the following criteria may not be enrolled.

1. 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%;

2. Intracranial hypertension or cerebral impaired consciousness;

3. Symptomatic heart failure or severe arrhythmia;

4. Symptoms of severe respiratory failure;

5. With other types of malignancy;

6. Diffuse intravascular coagulation;

7. Serum creatinine and/or urea nitrogen ≥ 1.5 times the normal value;

8. With sepsis or other uncontrollable infection;

9. Suffering from uncontrollable diabetes mellitus;

10. Severe mental disorders;

11. Have significant intracranial lesions on cranial MRI;

12. Organ transplantation (excluding haematopoietic stem cell transplantation) history;

13. Female patients (patients of childbearing potential) with positive blood HCG test;

14. Hepatitis (including hepatitis B and C) and positive screening for AIDS and syphilis.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The General Hospital of Western Theater Command

OTHER

Sponsor Role: collaborator

Zhaxin Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai

OTHER

Sponsor Role: collaborator

Shanghai Liquan Hospital

OTHER

Sponsor Role: collaborator

Ruijin Hospital

OTHER

Sponsor Role: collaborator

Beijing GoBroad Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jing Pan

Director of Dept of Hemato-Oncology and Immunotherapy

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Zhaxin Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai

Shanghai, Shanghai Municipality, China

Site Status: NOT_YET_RECRUITING

Shanghai Liquan Hospital

Shanghai, Shanghai Municipality, China

Site Status: NOT_YET_RECRUITING

The General Hospital of Western Theater Command PLA

Chengdu, Sichuan, China

Site Status: NOT_YET_RECRUITING

BeijingGoBroadH

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Shaocong Miao

Role: CONTACT

miaosc@gobroadhealthcare.com

86+ 18831006667

Facility Contacts

Tengyu Wang

Role: primary

miaosc@gobroadhealthcare.com

86+18831006667

Other Identifiers

BJGBYY-IIT-LCYJ-2024-004

Identifier Type: -

Identifier Source: org_study_id