A Clinical Study to Investigate the Safety and Efficacy of Off-the-Shelf iNKT Cell Injection Targeting CD33/CD70 in Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia

A Clinical Study to Investigate the Safety and Efficacy of Off-the-Shelf iNKT Cell Injection Targeting CD33/CD70 in Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia

This is a single-arm, open-label, dose-escalation, prospective exploratory clinical study intended to evaluate the safety, efficacy and cellular pharmacokinetics of GT737 cells in adult patients with relapsed/refractory acute myeloid leukemia (AML).

Inclusion Criteria:

• 1. Voluntarily participate in this clinical study, fully understand the study content, sign the informed consent form, and be willing to comply with all study procedures and complete all follow-up visits.
• 2. Aged between 18 and 75 years old (inclusive), with no restriction on gender.
• 3. Confirmed diagnosis of relapsed/refractory acute myeloid leukemia (AML) per the 2016 WHO Classification, with the specific definitions as follows:

Confirmed AML with bone marrow blasts ≥5% at screening, and meeting any one of the following criteria:

• Relapsed disease: Relapse after achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) following standard induction chemotherapy;

• Refractory disease: a) Failure to achieve CR/CRi after 2 cycles of induction chemotherapy; b) Relapse within 12 months of first remission with no response to subsequent re-treatment; c) Relapse after autologous or allogeneic hematopoietic stem cell transplantation; d) Failure to achieve CR/CRi after at least two lines of salvage therapy.

  • 4. Confirmed positive expression of CD33 or CD70 via flow cytometry and/or immunohistochemistry.
  • 5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
  • 6. Estimated survival of more than 12 weeks.
  • 7. Toxicities resulting from prior therapies must be stabilized and recovered to Grade ≤1 (alopecia and other toxicities with no significant clinical impact are excluded).
  • 8. Adequate hepatic, renal, pulmonary and cardiac function, meeting the following specific criteria:
  • o Estimated creatinine clearance (calculated via the Cockcroft-Gault formula) ≥60 mL/min;
  • o Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤2.5 times the upper limit of normal (ULN);
  • o Total bilirubin ≤1.5 mg/dL (participants with Gilbert's syndrome excluded from this criterion);
  • o Cardiac ejection fraction ≥50%, no evidence of pleural effusion on echocardiogram (ECHO), and no clinically significant abnormalities on electrocardiogram (ECG);
  • o Absence of clinically significant pleural effusion;
  • o Baseline oxygen saturation >92% while breathing room air.
  • 9. Females of childbearing potential: Serum or urine pregnancy test negative at screening (subjects with surgical sterilization or menopause for ≥2 years are not considered of childbearing potential). Must agree to use highly effective and reliable contraception for 1 year after receiving study treatment, and refrain from oocyte donation.
  • 10. Male participants: If sexually active with females of childbearing potential, must agree to use highly effective and reliable contraception for 1 year after receiving study treatment, and refrain from sperm donation.

Exclusion Criteria:

• 1. Prior history of central nervous system (CNS) leukemia; or intracranial magnetic resonance imaging (MRI)/PET-CT at screening suggestive of CNS leukemia; or malignant cells identified in cerebrospinal fluid (CSF).

• 2. Other untreated malignant neoplasms diagnosed within the past 5 years or concurrent malignancies (Exceptions: adequately treated cervical carcinoma in situ, localized cutaneous squamous cell carcinoma, basal cell carcinoma, localized prostate cancer, ductal carcinoma in situ of the breast, urothelial carcinoma ≤T1; participants with prostate cancer under active surveillance are eligible).

• 3. Prior receipt of CD33- or CD70-targeted cellular therapies including CAR-T, NK or iNKT cells (Excluding subjects previously treated with GT737 who qualify for re-treatment).

• 4. Systemic corticosteroids administered within 7 days prior to cell infusion (Exceptions: inhaled corticosteroids and subjects with prior allogeneic transplantation history).

• 5. History of hypersensitivity to any component of investigational products to be used in this study, including but not limited to GT737 cell infusion product, cyclophosphamide and fludarabine.

• 6. Uncontrolled suspected or confirmed fungal, bacterial, viral or other infections, or infections requiring intravenous (IV) antimicrobial therapy (Excluding prophylactic antimicrobial treatment).

  7. Positive test results for any of the following: human immunodeficiency virus (HIV) antibody, Treponema pallidum antibody, cytomegalovirus IgM (CMV-IgM), Epstein-Barr virus IgM (EBV-IgM).

• 8. Active hepatitis B (positive HBV-DNA) and/or active hepatitis C (positive HCV RNA).

Participants positive for HBsAg/HBcAb must undergo HBV-DNA testing; those with negative HBV-DNA may be enrolled. Post-enrollment, prophylactic antiviral therapy shall be administered if clinically indicated per investigator assessment.

Subjects with negative HCV antibody are eligible for enrollment. Participants with positive HCV antibody must receive HCV RNA testing and may be enrolled only if HCV RNA is negative.

• 9. Presence of any indwelling line or drainage tube (Exceptions: dedicated central venous access catheters such as Port-a-Cath and Hickman catheter).

• 10. Current or prior central nervous system disorders including seizures, cerebral ischemic/hemorrhagic events, dementia, cerebellar disease, or any autoimmune disease involving the CNS.

• 11. Cardiac involvement secondary to acute myeloid leukemia.

• 12. Occurrence of any of the following within 6 months prior to signing the informed consent form:

  • Uncontrolled congestive heart failure (New York Heart Association Class III-IV), angina pectoris, myocardial infarction, cardiomyopathy;
  • Stroke (Excluding lacunar infarction), coronary or peripheral artery bypass graft surgery;
  • Clinically significant arrhythmias (e.g., ventricular arrhythmia), markedly prolonged QT interval (corrected QTc ≥500 ms by Bazett's formula, as judged by the investigator);
  • Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg), uncontrolled diabetes mellitus;
  • Pulmonary embolism, diffuse pulmonary infiltrates, impaired pulmonary function;
  • Other medical conditions deemed unsuitable for study participation by the investigator.

• 13. Anticipated or potential need for emergency treatment within 6 weeks due to ongoing or imminent oncologic emergencies (e.g., tumor mass effect, tumor lysis syndrome).

• 14. Primary immunodeficiency disorders.

• 15. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months before enrollment requiring systemic anticoagulation therapy.

• 16. Any medical condition that may interfere with the assessment of safety or efficacy of the study treatment.

• 17. Live attenuated vaccines or mRNA vaccines administered within 8 weeks prior to lymphodepleting conditioning; inactivated vaccines administered within 4 weeks prior to lymphodepleting conditioning.

• 18. Females of childbearing potential who are pregnant or breastfeeding (Subjects with surgical sterilization or menopause for ≥2 years are not regarded as of childbearing potential).

• 19. Male or female participants unwilling to use contraceptive measures from the time of informed consent through 6 months after completion of study treatment.

• 20. Participants judged by the investigator to be unlikely to complete all study visits and procedures (including follow-up) or unable to comply with study participation requirements.

• 21. History of autoimmune disease within the past 2 years causing end-organ damage or requiring systemic immunosuppressive agents/systemic disease-modifying therapy (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, etc.).