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

Korábbi kezelés

• 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.
• 10. Current or prior central nervous system disorders including seizures, cerebral ischemic/hemorrhagic events, dementia, cerebellar disease, or any autoimmune disease involving the CNS.
• 15. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months before enrollment requiring systemic anticoagulation therapy.
• 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.

Más betegség

• 6. Uncontrolled suspected or confirmed fungal, bacterial, viral or other infections, or infections requiring intravenous (IV) antimicrobial therapy (Excluding prophylactic antimicrobial treatment).
  • 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.
• 11. Cardiac involvement secondary to acute myeloid leukemia.
• 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.
• 16. Any medical condition that may interfere with the assessment of safety or efficacy of the study treatment.
• 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.).

Laborértékek

• 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.

Életkor

• 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).

Egyéb

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

• 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.