The Safety and Efficacy of VGO-Cs01p in Patients With CD7-positive Relapsed/Refractory Acute T-lymphoblastic Leukemia

To learn if the VGO-Cs01p can help to control CD7-positive relapsed/refractory acute T-lymphoblastic leukemia (R/R T-ALL) in children.

This is a single-arm, open label, IIT clinical trial to evaluate the safety and efficacy of CD7 CAR NK cells in subjects with CD7-positive relapsed/refractory acute T-lymphoblastic leukemia (R/R T-ALL). 5\~9 subjects plan to be enrolled. In this study, safety and efficacy results will be used for dose escalation design at the same time, and three initial dose groups are set up. All subjects will be followed up to 12 months after infusion.

Eligibility Criteria:
Inclusion Criteria:

1. Age ≥2 and ≤18 years old, male or female;
2. Subjects who have relapse or refractory T-cell lymphoblastic leukemia (T-ALL) according to the standards of the NCCN Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2024.V6);
3. Meets the criteria for recurrent or refractory T-ALL, including: a) Recurrent: Reappearance of blasts in peripheral blood or bone marrow (\>25%) after complete remission or occurrence of extramedullary disease, and ineffectiveness of other treatments； b) Primary Refractory: Appearance of blasts in bone marrow ≥5% after 2 months standard induction chemotherapy, and no other treatment can be used as judged by the investigator;
4. After one cycle of other treatments (such as Olverembatinib combined with APG-125), the blasts remain≥5%;
5. Cell immunophenotyping confirmation of CD7 positive blasts \>80%;
6. Estimated survival period \>12 weeks;
7. Eastern Cooperative Oncology Group (ECOG) performance status score ≤1 or KPS \> 60;
8. Left ventricular ejection fraction ≥50%;
9. Pulmonary function ≤ Grade 1 dyspnea (CTCAE v5.0), normal oxygen saturation without oxygen supplementation;
10. TBil ≤ 3×ULN, AST and ALT ≤ 5×ULN, creatinine ≤ 1.6 mg/dl within 1 week prior to enrollment;
11. Negative serum pregnancy test for fertile women; fertile non-abstinent female patients must agree to use an effective contraceptive method from screening to 1 year after cell infusion. Fertile male patients' partners must agree to use effective contraception from screening to 1 year after cell infusion, and should not donate semen or sperm throughout the study;
12. The subject or their legal guardian voluntarily participates in the study, understands the information, purpose, and risks described in the informed consent form, and can provide a signed and dated informed consent form;
13. The subject and/or their parents or their legal guardian should voluntary and able to comply with all requirements of the trial.

Exclusion Criteria:

1. Extramedullary involvement of the central nervous system or testicular at screening.
2. Patients with a history of severe CNS diseases, such as uncontrolled seizures, stroke, severe brain damage resulting in speech impairment, psychiatric disorders, etc;
3. NYHA functional class III or IV heart failure;
4. Presence of disseminated intravascular coagulation;
5. Presence of severe autoimmune diseases or immune deficiency diseases;
6. Active GVHD requiring systemic treatment;
7. Presence of other severe diseases, presence of gastrointestinal ulcers or active gastrointestinal bleeding, currently undergoing anticoagulant or antiplatelet therapy, or judged by the investigator to pose unacceptable surgical or anesthesia risks;
8. Currently receiving systemic steroids or other immunosuppressive therapy prior to screening, and still need long-term use after enrollment as judged by the investigator (excluding inhaled or local use);
9. History or concurrent active malignant tumors within 3 years prior to enrollment;
10. Active HBV or HCV infection (HBV-DNA positive or HCV-RNA positive), HIV positive, or positive syphilis test;
11. Other severe or persistent active infections;
12. Adverse events related to previous systemic immunotherapy (including other investigational drugs or medical device interventions) prior to enrollment have not reduced to grade 1 severity or returned to baseline;
13. Platelet count remains low after intervention treatment (meeting clinical transfusion criteria) prior to enrollment；
14. Discontinuation of immunosuppressive agents for less than 2 weeks;
15. Participation in CAR-T cell therapy or gene therapy at any time prior to screening;
16. History of allergy to any component of the study product;
17. Vaccination or any surgery within the 4 weeks prior to screening;
18. Other situations as judged by the investigator may increase the subject's risk or interfere with study;
19. Pregnant or breastfeeding women;
20. Individuals assessed by the investigator to have potential hidden risks of disputes.