Clinical Study of Anti-CLL1-CD33-NKG2D Bicephali CAR-T for Relapsed/Refractory Acute Myeloid Leukemia

This clinical trial aims to assess the safety and efficacy of a novel CAR-T cell therapy in patients with relapsed/refractory acute myeloid leukemia (AML). The treatment involves the infusion of genetically modified anti-CLL1-CD33-NKG2D Bicephali CAR-T cells, a type of immunotherapy that enhances the body's immune system to target and destroy cancerous leukemia cells. The therapy is designed to specifically target AML cells by utilizing unique markers (CLL1, CD33, and NKG2D) on the surface of the leukemia cells.

Participants in this study will undergo T cell collection, which involves harvesting their own T cells through a procedure known as apheresis. These cells will then be modified in the laboratory to express the specific CAR-T receptors. Once the cells are modified, they will be re-infused back into the patient, with the goal of activating the immune system to fight off the leukemia.

This study will closely monitor adverse effects, including any side effects of the CAR-T therapy, such as cytokine release syndrome (CRS) or neurological effects, which are known risks of CAR-T treatments. Patients will be followed for a designated period to track response rates, including the reduction of leukemia cells, progression-free survival, and overall survival.

Participants will also undergo regular health assessments, including laboratory tests, imaging studies, and routine examinations, to evaluate both the effectiveness of the treatment and potential complications.

Eligibility for this study includes adult patients with relapsed/refractory AML, meaning their disease has returned after previous treatments or has not responded to standard therapies. This trial provides an opportunity for patients who have limited treatment options to receive access to an advanced, experimental treatment that may improve their outcomes.

Patients will be fully informed about the potential risks and benefits of participating in this study, and their participation will be voluntary. Detailed informed consent will be obtained before any study-related procedures are performed.

Inclusion criteria

Age: Patients must be ≥18 years old. Diagnosis: Confirmed diagnosis of relapsed or refractory acute myeloid leukemia (AML) as per the World Health Organization (WHO) criteria.

Prior Treatment: Must have failed at least one prior line of chemotherapy or targeted therapy.

Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

Adequate Organ Function:

Hematologic function: Absolute neutrophil count (ANC) ≥ 1,000/μL, platelet count ≥ 50,000/μL, and hemoglobin ≥ 8 g/dL (without transfusion support).

Renal function: Serum creatinine ≤ 1.5 x upper limit of normal (ULN). Liver function: Total bilirubin ≤ 2 x ULN, AST/ALT ≤ 2.5 x ULN. Informed Consent: The patient must be willing and able to provide written informed consent to participate in the study.

Eligible for Apheresis: Patients must be able to undergo the apheresis procedure to collect T cells for CAR-T cell modification.

Exclusion criteria

Active Central Nervous System (CNS) Leukemia: Presence of active leukemia in the CNS.

Pregnancy or Breastfeeding: Female patients who are pregnant or breastfeeding. Severe Active Infections: Active and uncontrolled infections, including HIV, hepatitis B or C, or any other severe systemic infections.

Other Malignancies: History of another malignancy (except for treated, localized cancers such as basal cell carcinoma) within the past 5 years.

Autoimmune Diseases: Active autoimmune diseases requiring systemic immunosuppressive therapy.

History of Severe Cytokine Release Syndrome (CRS): Any history of severe CRS or neurological toxicity following prior CAR-T cell therapy.

Allergy to Apheresis or CAR-T Cell Components: Known hypersensitivity to any of the components involved in the apheresis or CAR-T cell therapy procedure.

Uncontrolled Systemic Disease: Uncontrolled comorbid conditions, such as severe cardiovascular disease, uncontrolled hypertension, or severe pulmonary conditions.

Concurrent Participation in Another Clinical Trial: Participation in another clinical trial for AML or related conditions that may interfere with this study's treatment and outcomes.

Inability to Comply: Inability to comply with study procedures or follow-up requirements as per the investigator's judgment.