Allogeneic CD7 CAR γδ T Cells Therapy Recurrent/Refractory Leukemia

Clinical Study on the Safety and Efficacy of CD7 CAR-γδT Cell Injection for the Treatment of Relapsed/Refractory Leukemia

CD7 is highly expressed in T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoma. Approximately 10-30% of cute myeloid leukemia(AML) patients exhibit CD7 expression, particularly in early myeloid progenitor cell-derived AML (e.g., M0/M1 subtypes), mixed-phenotype acute leukemia (MPAL), and AML with high-risk genetic abnormalities (such as TP53 mutations or complex karyotypes). CD7-positive AML patients typically have poor prognosis, poor response to standard chemotherapy, and shorter overall survival (OS). Targeted CD7 cell therapies may represent a promising direction for the treatment of these diseases.

This study is a single-arm,open-label, dose-escalation clinical trial. It is planned to enroll 9-18 patients with CD7-positive relapsed/refractory T-ALL/LBL and relapsed/refractory AML. The study will use a 3+3 design for dose escalation, with three initial dose groups: 1*10^8 CAR+ cells, 3*10^8 CAR+ cells, and 6*10^8 CAR+ cells.

Inclusion criteria:

1. Age ≥ 14 years, no gender restrictions;

2. Diagnosed with TALL/LBL according to the NCCN Acute Lymphoblastic Leukemia Clinical Practice Guidelines (2023.V2); or diagnosed with AML according to the NCCN Acute Myeloid Leukemia Clinical Practice Guidelines (2023.V6);

3. Meet the criteria for relapsed or refractory T-ALL/LBL, including any of the following:

   1. Relapsed: after achieving complete remission(CR), peripheral blood or bone marrow shows >5% blast cells or extramedullary lesions in any site;
   2. Refractory: primary refractory cases that did not achieve CR after standard induction chemotherapy.

   Or meets the criteria for relapsed or refractory AML, including any of the following:

   1. Relapsed: leukemic cells reappear in peripheral blood or ≥5% of blast cells in bone marrow (excluding other causes such as bone marrow regeneration after consolidation chemotherapy) or extramedullary leukemic cell infiltration after achieving CR;
   2. Refractory: primary cases that remain unresponsive after two cycles of standard treatment; Patients who relapse within 12 months after consolidation therapy following CR; patients who relapse after 12 months and are unresponsive to conventional chemotherapy; patients with two or more relapses; patients with persistent extramedullary leukemia;

4. Cytological confirmation of tumor cell immunophenotyping as CD7-positive during screening;

5. Expected survival time exceeding 3 months;

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;

7. Organ function meets the following requirements:

   • Liver function: ALT ≤ 3 × ULN; AST ≤ 3 × ULN; Total bilirubin ≤ 3.0 × ULN.
   • Renal function must meet the following criteria: serum creatinine ≤ 1.5 × upper limit of normal (ULN);
   • Cardiac function: echocardiogram showing left ventricular ejection fraction ≥ 50%;
   • Pulmonary function: normal oxygen saturation without oxygen supplementation.

8. Female participants of childbearing potential and male participants whose partners are of childbearing potential must use medically approved contraceptive measures or abstain from sexual intercourse during the study treatment period and for at least 6 months after the study treatment period. Female participants of childbearing potential must have a negative serum HCG test within 7 days prior to study enrollment and must not be breastfeeding.

9. No significant genetic disorders;

10. The subject or their legal guardian voluntarily participates in this study, understands the trial information, objectives, and risks described in the informed consent form, and can provide a signed and dated informed consent form;

11. The subject or their legal guardian is willing and able to comply with all trial requirements.

Exclusion criteria:

1. Patients with a history of severe central nervous system disorders, such as uncontrolled epileptic seizures, stroke, severe brain injury with aphasia, paralysis, dementia, Parkinson's disease, or mental disorders;
2. Heart failure classified as NYHA functional class III or IV;
3. Any of the following unstable cardiovascular conditions occurring within the past 6 months prior to screening (including but not limited to): unstable angina, cerebral ischemia or cerebrovascular accident, myocardial infarction, severe arrhythmias requiring medication (such as rapid atrial fibrillation, high-degree atrioventricular block, ventricular tachycardia, ventricular fibrillation, or torsades de pointes); Undergone coronary angioplasty, coronary artery stent implantation, or coronary artery bypass surgery; experienced thrombosis or embolism events (e.g., cerebrovascular events [including transient ischemic attacks, but excluding lacunar cerebral infarction], deep vein thrombosis [excluding deep vein thrombosis caused by PICC catheter placement], pulmonary embolism, etc.);
4. Presence of disseminated intravascular coagulation;
5. Presence of severe autoimmune diseases or immunodeficiency disorders;
6. Presence of active graft-versus-host disease requiring ongoing systemic treatment;
7. Subjects currently receiving systemic steroid or other immunosuppressive therapy prior to screening, and who, as determined by the investigator, will require long-term use of such therapy after enrollment (excluding inhaled or topical use);
8. Other severe medical conditions deemed inappropriate for enrollment by the investigator (e.g., uncontrolled hypertension or diabetes, severe renal insufficiency, severe pulmonary dysfunction, etc.);
9. Active HBV or HCV infection (HBV-DNA positive or HCV-RNA positive), HIV-positive status, or positive syphilis test results;
10. Other severe or persistent active infections;
11. Adverse events related to systemic immunotherapy (including other investigational drugs or medical device interventions) prior to screening have not yet decreased to Grade 1 severity or returned to baseline status;
12. Immunosuppressive agents have been discontinued for less than 2 weeks;
13. Those who have received CAR-T cell therapy in the past;
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 the risk to the subject or interfere with trial results.