Overview

This is a Phase 1/Phase 2 open-label, single-arm clinical study of GP350 CAR-T for Relapse/Refractory and Epstein-Barr virus infection associated lymphoid neoplasms.

Each participant will undergo leukapheresis after enrolment, receive treatment of the conditioning chemotherapy, and an intravenous infusion of CAR-T cells.

Each participant will proceed through the following study procedures:

• Screening
• Enrollment/Leukapheresis
• Conditioning chemotherapy
• CAR T treatment
• Post-treatment assessment
• Long-term follow-up

Eligibility

Inclusion Criteria:

1. Diagnosis: Confirmed diagnosis of lymphoid neoplasms according to WHO-HAEM5 (Alaggio R. et al. doi:10.1038/s41375-022-01620-2);
2. Disease Assessment:
   1. Criteria for Relapsed/Refractory lymphoid neoplasms: Meeting any one of the following three conditions: ① Failure to achieve at least a partial response (PR) per Lugano criteria after two cycles of standard first-line therapy; ② Disease progression within six months after achieving a response to first-line therapy, or progression after six months with no response to the original first-line or second-line regimen; ③ Relapse after hematopoietic stem cell transplantation.
   2. Criteria for EBV Infection: Meeting any one of the following three conditions: ① Peripheral blood (plasma or whole blood) EBV DNA load ≥ 10³ copies/ml by quantitative PCR; ②Tumor cell GP350 positivity (≥10% of tumor cells by immunohistochemistry or flow cytometry); ③ Serological detection of EBV antibodies indicating any of the following: positive anti-VCA-IgM; positive anti-EA-IgG; or simultaneous positivity for anti-VCA-IgM, anti-VCA-IgG, and anti-EBNA-IgG.
   3. At least one evaluable lymphoma lesion according to Lugano criteria, or confirmed active lytic EBV infection.
3. Performance Status: ECOG score 0-2 and expected survival ≥3 months;
4. Age: 18-70 years, regardless of sex;
5. Hematologic Criteria:
   • Absolute neutrophil count (ANC) ≥1.0×10⁹/L;
   • Hemoglobin \>60 g/L;
   • CD3+ T-cell count \>0.5×10⁹/L;
   • Platelet count \>30×10⁹/L;
6. Organ Function:
   • Creatinine clearance ≥60 mL/min;
   • ALT/AST ≤2× upper limit of normal (ULN);
   • Total bilirubin ≤2× ULN;
   • Left ventricular ejection fraction (LVEF) ≥50%, no pericardial effusion, and no clinically significant ECG abnormalities;
   • Minimal or no pleural/ascitic fluid;
   • Oxygen saturation ≥95%;
7. Contraception:
   • Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception until the last follow-up;
   • Male participants with fertile partners must agree to use effective contraception until the last follow-up;
8. Informed Consent: Psychologically stable, capable of understanding the study's purpose and procedures, willing to participate voluntarily, and able to provide signed informed consent and comply with protocol requirements.

Exclusion Criteria:

1. Active Infections: Presence of active hepatitis A, B, or C infection, or other uncontrolled severe active infections (excluding EBV infection);
2. Immunosuppression:
   • History of acquired immunodeficiency syndrome (AIDS);
   • Chronic use of immunosuppressants (including corticosteroids at doses equivalent to \>15 mg/day of prednisone) for other conditions;
3. Cardiac Dysfunction:
   1. NYHA Class III or IV congestive heart failure;
   2. Myocardial infarction or coronary artery bypass grafting within the past 6 months;
   3. Clinically significant ventricular arrhythmia or unexplained syncope;
   4. History of severe non-ischemic cardiomyopathy;
   5. Cardiac insufficiency (left ventricular ejection fraction \<45%) within 8 weeks prior to apheresis;
4. Pregnancy/Contraception:
   • Pregnant or lactating women;
   • Participants (male or female) unwilling to use contraception;
5. Hepatic/Renal Impairment:
   • AST/ALT \>3× upper limit of normal (ULN);
   • Total bilirubin \>3× ULN;
   • Creatinine clearance \<60 mL/min;
6. Allergies: History of severe hypersensitivity to any study drugs;
7. Prior Stem Cell Transplant: Must have discontinued immunosuppressants for \>6 weeks post-transplant with no signs of graft-versus-host disease (GVHD);
8. Other Exclusionary Conditions: Any other condition deemed unsuitable by the investigator (e.g., coagulation disorders, hemolytic anemia, etc.).