Clinical trial NCT06326021: Optimised CD33 (FL-33) CAR T Therapy for Refractory/Relapsed Acute Myeloid Leukaemia
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Refractory/Relapsed Acute Myeloid Leukaemia
Lead sponsor: Beijing GoBroad Hospital
Sponsor class: OTHER
Collaborators: name: The General Hospital of Western Theater Command
name: Zhaxin Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai
name: Shanghai Liquan Hospital
First posted: 2024-03-22
Enrollment: 27
Sex: ALL
Minimum age (years): 1
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Patients who met all the inclusion criteria were eligible for enrolment.

  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.

Primary outcomes:
measure: Dose-limiting toxicity(DLT)
timeFrame: 21 days
measure: Adverse events (AEs)
timeFrame: 30 days
Secondary outcomes:
measure: Long-term Adverse events (AEs)
timeFrame: From 30 days after FL-33 CAR T infusion to 2 years
measure: Objective Response Rate (ORR)
timeFrame: 15, 30, 90 days
measure: Duration of response (DOR)
timeFrame: Up to 2 years
measure: Progression-free survival (PFS)
timeFrame: Up to 2 years
measure: Overall survival (OS)
timeFrame: Up to 2 years
measure: The persistence of FL-33 CAR T cells
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhaxin Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Liquan Hospital
state: Shanghai
city: Chengdu
country: China
facility: The General Hospital of Western Theater Command PLA
state: Sichuan
city: Beijing
country: China
facility: BeijingGoBroadH
Study officials:
References: