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

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).

Inclusion criteria

• Age ≥18 and <70 years old, gender not specified;
• Diagnosed with B-ALL or AML according to the World Health Organization (WHO) classification of hematopoietic and lymphoid tissue tumors (2022 version);
• 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;
• 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;
• Estimated survival >12 weeks;
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤2;
• Left ventricular ejection fraction (LVEF) ≥50%;
• Pulmonary function ≤Grade 1 dyspnea (CTCAE v5.0), normal oxygen saturation without oxygen supplementation;
• Total bilirubin (TBil) ≤3×upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5×ULN, creatinine ≤1.6mg/dL;
• 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.
• 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.
• The subject and their legal guardian are willing and able to comply with all trial requirements.

Exclusion criteria

• 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.;
• New York Heart Association (NYHA) functional class III or IV heart failure;
• 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.
• Presence of disseminated intravascular coagulation;
• Severe autoimmune diseases or immunodeficiency diseases;
• Active graft-versus-host disease requiring continued systemic therapy;
• 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);
• 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;
• Presence of other severe medical conditions as determined by the investigator, such as uncontrolled hypertension or diabetes, severe renal insufficiency, severe pulmonary dysfunction, etc.;
• Active HBV or HCV infection (HBV-DNA positive or HCV-RNA positive), HIV positive, or syphilis positive;
• Other severe or persistent active infections;
• 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;
• Discontinuation of immunosuppressants within 2 weeks prior to screening;
• History of allergy to any component of the cell product;
• Vaccination or any surgical procedure within 4 weeks prior to screening;
• Other conditions deemed by the investigator to potentially increase subject risk or interfere with trial results.