Optimized CAR T Therapy for Acute Myeloid Leukaemia

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 testing a new CAR T therapy to see if it can safely help people with tough cases of acute myeloid leukaemia get better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 1 Year to 70 Years
• Sex: All
• Sponsor: Beijing GoBroad Hospital (Academic / other)
• Drugs / interventions: CAR T, chemotherapy, CAR-T
• Locations: 4 sites (Shanghai, Shanghai Municipality and 3 other locations)
• Trial ID: NCT06326021 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and efficacy of FL-33 CAR T therapy in patients with refractory or relapsed acute myeloid leukaemia. It is a multi-center, open-label, non-randomized, single-arm phase 1 trial that aims to determine the optimal biological dose of CAR T cells. The study will assess various endpoints including dose-limiting toxicity, adverse events, and response rates over a period of time following CAR T infusion. Participants will receive autologous or donor-derived FL-33 CAR T therapy based on their eligibility criteria.

Who should consider this trial

Good fit: Ideal candidates include patients aged 1-70 years with CD33 positive refractory or relapsed acute myeloid leukaemia.

Not a fit: Patients with severe allergies or those not expressing CD33 on their tumor cells may not benefit from this therapy.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with difficult-to-treat acute myeloid leukaemia.

How similar studies have performed: Other studies using CAR T therapy for hematological malignancies have shown promising results, indicating potential for success in this approach.

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.

Where this trial is running

Shanghai, Shanghai Municipality and 3 other locations

• Zhaxin Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai — Shanghai, Shanghai Municipality, China (Not_yet_recruiting)
• Shanghai Liquan Hospital — Shanghai, Shanghai Municipality, China (Not_yet_recruiting)
• The General Hospital of Western Theater Command PLA — Chengdu, Sichuan, China (Not_yet_recruiting)
• BeijingGoBroadH — Beijing, China (Recruiting)

Study contacts

• Study coordinator: Shaocong Miao

Conditions Refractory/Relapsed Acute Myeloid Leukaemia