CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

Only patients who meet all the following criteria can be included in the group:

1. CD7-positive refractory or relapsed T-cell malignancies with progression or intolerance after all standard treatments, limited prognosis from currently available treatments and no available treatment options (e.g. HSCT or chemotherapy).
2. Tumor cells in bone marrow or cerebrospinal fluid are positive for CD7 antigen by flow cytometry or tumour tissue is positive for CD7 by immunohistochemistry (CD7 antigen positivity by flow cytometry: \>80% of tumour cells expressing CD7 with a mean fluorescence intensity \[MFI\] of CD7 similar to that of normal T cells are considered to have fully positive expression; \>80% of tumor cells expressing CD7 but with an MFI of CD7 at least 1 log lower than that of normal T cells are considered to have low expression \[dim\]; tumor cells with a CD7 expression rate between 20-80% are considered to have partial expression; CD7 antigen positivity by pathological immunohistochemistry: \>30%);
3. Male or female, age 1-70 years;
4. No severe allergic constitution;
5. Eastern Cooperative Oncology Group (ECOG) performance status score (Oken et al., 1982) of 0-2;
6. Life expectancy of at least 60 days as determined by the investigator;
7. Provide a signed informed consent form prior to any screening procedures; subjects volunteering to participate in the study should be capable of understanding and signing the informed consent form and be willing to follow the study visit schedule and associated study procedures as specified in the protocol. Subjects aged 19-70 years old need to be sufficiently aware and capable of signing the informed consent form; subjects aged 1-7 years can be recruited after legal guardians or patient advocates sign the informed consent form; subjects aged 8-18 years need to be sufficiently aware and able to sign the informed consent form, and their legal guardians or patient advocates also need to sign the informed consent form.

Exclusion Criteria:

Patients with at least one of the following conditions are excluded:

1. Intracranial hypertension or unconscious;
2. Acute heart failure or severe arrhythmia;
3. Acute respiratory failure;
4. Other types of malignant tumors;
5. Diffuse intravascular coagulation;
6. Serum creatinine and/or blood urea nitrogen over 1.5 times the normal value;
7. Sepsis or other uncontrolled infection;
8. Uncontrolled diabetes mellitus;
9. Severe psychological disorder;
10. Obvious cranial lesions by cranial MRI;
11. Allergic constitution;
12. Organ recipients;
13. Pregnant or breastfeeding;
14. Active, uncontrolled infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or treponema pallidum (TP).

主要终点：Dose-Limiting Toxicity (DLT) in phase I · Type and incidence of dose-limiting toxicity (DLT) within 21 days after CD7 CAR T-cell infusion · 21 days post infusion；Overall Response Rate (ORR) in phase II · Overall response rate (ORR), which includes CR, CRh, CRi, MLFS, aplastic marrow for blood and bone marrow; central nervous system (CNS) remission; CR and PR for lymphomatous extramedullary disease per National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2023 of Acute Lymphoblastic Leukemia at 3 months (± 1 week) post CD7 CAR T-cell infusion in refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/T-LBL) patients treated with CD7 CAR T cells · 3 months (± 1 week) post infusion
次要终点：Overall Response Rate (ORR) in phase I；Safety in phase II；Progression-Free Survival (PFS) in phase II；Duration of Remission (DOR) in phase II；Overall Survival (OS) in phase II；Levels of CD7 CAR-T Cells in phase II；Levels of CAR transgene in phase II；Levels of immune cells in phase II

• Arm-1 · EXPERIMENTAL · Autologous CD7 CAR T-cell treatment
• Arm-2 · EXPERIMENTAL · Prior-HSCT donor-derived CD7 CAR T-cell treatment
• Arm-3 · EXPERIMENTAL · New donor-derived CD7 CAR T-cell treatment

This is a multi-center, open-label, non-randomized, phase I/II trial. Patients with refractory or relapsed T-cell malignancies will receive autologous, prior-HSCT donor-derived or new donor-derived CD7 CAR T cells according to their HSCT history, peripheral blood leukemia burden and at their discretion. The primary objective is to learn about the safety of autologous, prior-HSCT donor-derived and new donor-derived CD7 CAR T-cell therapy in patients with refractory or relapsed T-cell acute lymphoblastic leukemia and lymphoma (r/r T-ALL/T-LBL) in phase I and to learn about the efficacy of autologous, prior-HSCT donor-derived and new donor-derived CD7 CAR T-cell therapy in patients with refractory or relapsed T-cell acute lymphoblastic leukemia and lymphoma (r/r T-ALL/T-LBL) in phase II. The primary endpoint is type and incidence of dose limiting toxicity (DLT) within 21 days after CD7 CAR T-cell infusion in phase I and overall response rate (ORR), which includes CR, CRh, CRi, MLFS, aplastic marrow for blood and bone marrow; central nervous system (CNS) remission; CR and PR for lymphomatous extramedullary disease according to National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2023 of Acute Lymphoblastic Leukemia at 3 months (± 1 week) post CD7 CAR T-cell infusion in refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/T-LBL) patients treated with CD7 CAR T cells in phase II. A total number of 80 subjects will be enrolled.