GP350 CAR-T for Relapse/Refractory and Epstein-Barr Virus Infection Associated Lymphoid Neoplasms
NCT07306156 · Phase 1, Phase 2 · Hefei, Anhui, China
- Condition
- Lymphoma
- Disease stage
- Stage I-IV
- Phase
- Phase 1, Phase 2
- Study type
- BIOLOGICAL
- Intervention
- GP350 CAR-T
- Age
- 18 Years to 70 Years
- Gender
- All
- Sponsor
- Zhimin Zhai
- Research institution
- Zhimin Zhai
- Facility
- The Second Affiliated Hospital of Anhui Medical University
- Research center
- The Second Affiliated Hospital of Anhui Medical University
Summary
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
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.).
Primary outcomes
Overall Response Rate (ORR); EBV DNA clearance rate; Treatment Emergent Adverse Event (TEAE)
Secondary outcomes
Progression-Free Survival (PFS); Overall Survival (OS)