GP350 CAR-T for Relapse/Refractory and Epstein-Barr Virus Infection Associated Lymphoid Neoplasms

Official title

GP350 CAR-T Cells for Relapse/Refractory and Epstein-Barr Virus Infection Associated Lymphoid Neoplasms, an Open-label, Single-arm Clinical Trial

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

Interventions

• Biological GP350 CAR-T
  Lymphodepletion chemotherapy with fludarabine (25 mg/m²/day) and cyclophosphamide (250 mg/m²/day) should be administered for 2-3 consecutive days, with the final dose completed 48 hours before infusion. Alternatively, investigators may individualize this regimen based on the subject's specific clinical circumstances. The target dose of GP350 CAR-T cells is 1.0-5.0×10⁶ CAR-T cells per kilogram of body weight, administered via intravenous injection. (The actual infused dose is allowed to vary with

Primary outcome measures

• Overall Response Rate (ORR) [Time frame: Month 12 post CAR-T infusion]
• EBV DNA clearance rate [Time frame: Month 12 post CAR-T infusion]
• Treatment Emergent Adverse Event (TEAE) [Time frame: Within 3 months post-infusion]

Secondary outcome measures (2)

• Progression-Free Survival (PFS) [Time frame: 1 yesr post CAR-T infusion]
• Overall Survival (OS) [Time frame: 1 yesr post CAR-T infusion]

Eligibility criteria

Inclusion criteria

• Diagnosis: Confirmed diagnosis of lymphoid neoplasms according to WHO-HAEM5 (Alaggio R. et al. doi:10.1038/s41375-022-01620-2);
• Disease Assessment:

• 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.
• 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.
• At least one evaluable lymphoma lesion according to Lugano criteria, or confirmed active lytic EBV infection.
• Performance Status: ECOG score 0-2 and expected survival ≥3 months;
• Age: 18-70 years, regardless of sex;
• 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;
• 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%;
• 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;
• 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

• Active Infections: Presence of active hepatitis A, B, or C infection, or other uncontrolled severe active infections (excluding EBV infection);
• 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;
• Cardiac Dysfunction:

• NYHA Class III or IV congestive heart failure;
• Myocardial infarction or coronary artery bypass grafting within the past 6 months;
• Clinically significant ventricular arrhythmia or unexplained syncope;
• History of severe non-ischemic cardiomyopathy;
• Cardiac insufficiency (left ventricular ejection fraction <45%) within 8 weeks prior to apheresis;
• Pregnancy/Contraception:

• Pregnant or lactating women;
• Participants (male or female) unwilling to use contraception;
• Hepatic/Renal Impairment:

• AST/ALT >3× upper limit of normal (ULN);
• Total bilirubin >3× ULN;
• Creatinine clearance <60 mL/min;
• Allergies: History of severe hypersensitivity to any study drugs;
• Prior Stem Cell Transplant: Must have discontinued immunosuppressants for >6 weeks post-transplant with no signs of graft-versus-host disease (GVHD);
• Other Exclusionary Conditions: Any other condition deemed unsuitable by the investigator (e.g., coagulation disorders, hemolytic anemia, etc.).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Affiliated Hospital of Anhui Medical University — Hefei

Identifiers

NCT: NCT07306156 · TXB2025-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗