A Clinical Study of HY035 Cell Injection in the Treatment of CD7-positive Relapsed or Refractory Hematologic Malignancies

A Clinical Study on the Safety and Efficacy of HY035 Cell Injection in the Treatment of CD7-positive Relapsed or Refractory Hematologic Malignancies

This study is a single-arm, open-label, non-randomized clinical trial aimed at evaluating the safety, tolerability and preliminary efficacy of HY035 cell injection in the treatment of patients with CD7-positive relapsed or refractory hematologic malignancies.

Inclusion Criteria:

1. Patients who voluntarily signs the informed consent form;

2. Age 3 and 70 years, any gender;

3. Diagnosed with CD7-positive refractory or relapsed hematologic malignancies (including acute T-lymphoblastic leukemia/lymphoblastic lymphoma, acute myeloid leukemia, NK- or T-cell-derived non-Hodgkin lymphoma, etc.);

4. By flow cytometry, tumor cells expressing CD7 account for ≥80%; or confirmed by immunohistochemistry, tumor cells expressing CD7 account for ≥30%;

5. During the screening period, acute T lymphoblastic leukemia/lymphoblastic lymphoma and acute myeloid leukemia must meet the requirement that the proportion of bone marrow blasts and immature lymphocytes is ≥5%; extramedullary lesions or non-Hodgkin lymphoma must have measurable lesions on imaging: the longest diameter of nodal lesions must be greater than 1.5 cm, and the longest diameter of extranodal lesions must be greater than 1.0 cm (see "Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification").

6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 or Lansky/Karnofsky performance score≥60;

7. Adequate organ function, meeting the following criteria (except for liver function abnormalities caused by tumor infiltration):

   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal (ULN);
   • Total serum bilirubin ≤ 2 × ULN, unless accompanied by Gilbert's syndrome; patients with Gilbert's syndrome can be included if total bilirubin ≤ 3 × ULN and direct bilirubin ≤ 1.5 × ULN.
   • Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 60 mL/min/1.73 m² (Cockcroft and Gault formula);
   • Minimum pulmonary reserve, defined as ≤ grade 1 dyspnea and blood oxygen saturation > 91% without supplemental oxygen;
   • International normalized ratio (INR) ≤ 1.5 × ULN, and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN;

8. The subjects whose partners are fertile agree to use effective contraceptive measures throughout the treatment period and for 24 months after the treatment, and during this period, they are not allowed to donate eggs/sperm for assisted reproduction. Female subjects of childbearing age (women who have undergone sterilization surgery or have been menopausal for ≥12 months are not considered fertile) have negative urine pregnancy or blood pregnancy tests during the screening period.

9. Willing to undergo hematopoietic stem cell transplantation.

Exclusion Criteria:

1. Patients with active central nervous system (CNS) leukemia or CNS involvement of lymphoma (CNS-3 as defined by NCCN guidelines, or CNS-2 with neurological symptoms), and without other active central nervous system diseases (such as epilepsy, cerebrovascular disease, etc.) or psychiatric disorders; (patients with CNS disease symptoms must undergo lumbar puncture and MRI to rule out CNS infiltration).

2. Patients with genetic syndromes associated with bone marrow failure, such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndromes.

3. Patients who had acute graft-versus-host disease (GvHD) or moderate to severe extensive chronic GvHD within 4 weeks prior to screening.

4. Pregnant or breastfeeding women.

5. Active systemic autoimmune diseases or connective tissue diseases;

6. Active bleeding;

7. Concurrent active infection during the screening period (such as sepsis, bacteremia, fungemia, uncontrolled pulmonary infection, and active tuberculosis) that requires treatment;

8. Positive hepatitis B surface antigen (HBsAg) or detectable HBV DNA, positive hepatitis C antibody (HCV-Ab), positive syphilis treponemal antibody (TP-Ab), positive HIV antibody; EBV DNA or CMV DNA above the detection limit, meeting any one of these criteria.

9. Major surgery within 4 weeks prior to screening, deemed unsuitable for enrollment by the investigator.

10. History of or current other malignancies within the past five years, except for tumors with negligible risk of metastasis or death and considered curable, such as adequately treated cervical carcinoma in situ, basal cell carcinoma of the skin, etc.

11. The patient's cardiovascular system meets any of the following conditions:

    • Left ventricular ejection fraction (LVEF) ≤45% (ECHO);
    • New York Heart Association (NYHA) class III or IV congestive heart failure;
    • Serious arrhythmias requiring treatment, including QTc interval ≥480 ms (QTcB = QT/RR^1/2);
    • Uncontrolled hypertension (systolic BP ≥160 mmHg and/or diastolic BP ≥100 mmHg), pulmonary hypertension, or unstable angina;
    • History of myocardial infarction or coronary artery bypass grafting/stent placement within 12 months prior to administration;
    • Clinically significant valvular disease;
    • Other cardiac conditions deemed unsuitable for enrollment by the investigator.

12. Presence of clinically significant pleural effusion, pericardial effusion, or ascites during screening;

13. Known hypersensitivity to any component of the study drug;

14. Vaccination with live vaccines within 6 weeks prior to screening;

15. Previous treatment with anti-CD7 therapy;

16. Expected life expectancy of less than 3 months;

17. History of solid organ transplantation;

18. Participation in other interventional clinical studies within 1 month prior to cell reinfusion, receipt of active investigational drug treatment, or intentional participation in another clinical trial or receiving antitumor treatment not specified in the protocol during the study;

19. Other situations deemed by the investigator as unsuitable for participation in this clinical trial.