Hema-NeoTIL01 Cell Infusion Therapy in Relapsed/Refractory Acute Leukemia

This clinical trial aims to investigate the safety, optimal dosage, and effectiveness of autologous tumor-specific T cells, known as Hema-NeoTIL0 in treating relapsed/refractory B-ALL/AML.

Primary Objective:

To assess the safety of Hema-NeoTIL01 in the treatment of relapsed/refractory acute leukemia (B-ALL/AML).

Secondary Objective:

To evaluate the efficacy of Hema-NeoTIL01 in relapsed/refractory acute leukemia (B-ALL/AML).

Eligibility Criteria:
Inclusion Criteria:

1. Age ≥18 and \<70 years old, gender not specified;
2. Diagnosed with B-ALL or AML according to the World Health Organization (WHO) classification of hematopoietic and lymphoid tissue tumors (2022 version);
3. Meet the diagnosis of relapsed/refractory leukemia, excluding isolated extramedullary relapse; For relapsed or refractory ALL, including any of the following situations: a) Relapse: Peripheral blood or bone marrow recurrence of primitive cells \>5% or extramedullary lesions appear again after complete remission; b) Refractory: Primary refractory patients who fail to achieve complete remission after standard induction chemotherapy; Or meet the diagnosis of relapsed or refractory AML, including any of the following situations: a) Relapse: Recurrence of primitive cells \>5% in bone marrow after complete remission (except for reasons such as bone marrow regeneration after consolidation chemotherapy) or extramedullary infiltration of leukemia cells; b) Refractory: Patients who have failed two cycles of standard treatment; those who relapse within 12 months after CR after consolidation therapy; those who relapse after 12 months and are ineffective after conventional chemotherapy; those with two or more relapses; those with persistent extramedullary leukemia;
4. Patients who have previously received ineffective/relapsed CAR-T cell therapy may be included in this study, provided that the efficacy evaluation of CAR-T therapy has been completed and evaluated as NR, or relapse after remission of CAR-T therapy;
5. Estimated survival \>12 weeks;
6. Eastern Cooperative Oncology Group (ECOG) performance status score ≤2;
7. Left ventricular ejection fraction (LVEF) ≥50%;
8. Pulmonary function ≤Grade 1 dyspnea (CTCAE v5.0), normal oxygen saturation without oxygen supplementation;
9. Total bilirubin (TBil) ≤3×upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5×ULN, creatinine ≤1.6mg/dL;
10. Pregnancy test must be negative, and fertile non-abstinent female patients must agree to use effective contraception from the start of self-screening to 1 year after cell infusion. Fertile male patients with fertile partners must agree to use effective contraception from the start of self-screening to 1 year after cell infusion, and should not donate semen or sperm throughout the study period.
11. The subject and their legal guardian voluntarily participate in this study, understand the trial information and objectives, and provide informed consent with a signed and dated signature.
12. The subject and their legal guardian are willing and able to comply with all trial requirements.

Exclusion Criteria:

1. Patients with a history of severe central nervous system diseases, such as uncontrolled seizures, stroke, severe brain injury resulting in aphasia, paralysis, dementia, Parkinson's disease, psychiatric disorders, etc.;
2. New York Heart Association (NYHA) functional class III or IV heart failure;
3. Any unstable diseases occurring within 6 months before screening (including but not limited to): unstable angina, ischemic or cerebrovascular accidents, myocardial infarction, severe arrhythmias requiring drug treatment (such as rapid atrial fibrillation, high-degree atrioventricular block, ventricular tachycardia, ventricular fibrillation, or torsades de pointes), cardiac catheterization or coronary artery stenting, or coronary artery bypass surgery, thrombotic or embolic events.
4. Presence of disseminated intravascular coagulation;
5. Severe autoimmune diseases or immunodeficiency diseases;
6. Active graft-versus-host disease requiring continued systemic therapy;
7. Subjects receiving systemic corticosteroids or other immunosuppressive therapy before screening, and the investigator determines that they will continue to use long-term therapy after enrollment (excluding inhalation or local use);
8. History of or concomitant active malignant tumors, excluding cured non-invasive basal cell or squamous cell skin cancer, uterine cervical carcinoma in situ or localized prostate cancer or breast ductal carcinoma in situ without recurrence for at least 2 years;
9. Presence of other severe medical conditions as determined by the investigator, such as uncontrolled hypertension or diabetes, severe renal insufficiency, severe pulmonary dysfunction, etc.;
10. Active HBV or HCV infection (HBV-DNA positive or HCV-RNA positive), HIV positive, or syphilis positive;
11. Other severe or persistent active infections;
12. Severity of adverse events related to previous systemic immunotherapy (including other investigational drugs or medical device interventions) at screening not reduced to grade 1 or baseline status;
13. Discontinuation of immunosuppressants within 2 weeks prior to screening;
14. History of allergy to any component of the cell product;
15. Vaccination or any surgical procedure within 4 weeks prior to screening;
16. Other conditions deemed by the investigator to potentially increase subject risk or interfere with trial results.