Overview
This study aims to investigate a novel therapeutic strategy of integrated radiotherapy before autologous stem cell transplantation (ASCT) sequential chimeric antigen receptor T-cell(CAR-T) therapy for patients with relapsed/refractory(R/R) aggressive B-cell non-Hodgkin lymphoma (B-NHL). By evaluating the efficacy and safety of this multimodal approach, we seek to provide a theoretical foundation and clinical data to optimize outcomes for relapsed/refractory aggressive B-NHL patients.
Description
This trial will enroll R/R aggressive B-NHL patients aged ≥18 years who have undergone at least two prior lines of systemic therapy. Participants will be stratified into two cohorts based on post-salvage therapy disease status:
Cohort 1 (PET/CT-, ctDNA+): Patients will receive low-dose radiotherapy (RT) combined with reduced-intensity SEAM/TB chemotherapy as a conditioning regimen, followed by ASCT and sequential CAR-T therapy.
Cohort 2 (PET/CT+, ctDNA+): Patients will receive high-dose RT combined with reduced-intensity SEAM/TB chemotherapy as a conditioning regimen, followed by ASCT and sequential CAR-T therapy.
All patients completing the combined ASCT-CAR-T protocol will undergo longitudinal follow-up for safety, efficacy survival outcomes .
Eligibility
Inclusion Criteria:
- Age ≥18 years.
- Histologically confirmed aggressive B-NHL.
- Life expectancy >3 months.
- Appropriate organ function:
Cardiac function: cardiac ejection fraction ≥50%; Liver function: alanine aminotransferase and glutamic aminotransferase ≤ 2 times the upper limit of normal values; renal function: serum creatinine clearance ≥80 mL/min; serum creatinine <160 mmol/L Lung function: SPO2>91% without oxygen intake
- Adequate bone marrow reserve defined as:
hemoglobin ≥90 g/L. platelet count ≥70 x 10^9/L. absolute neutrophil count ≥1.5 x 10^9/L.
- The patient is capable of understanding and willing to provide written informed consent.
- Subjects of childbearing or childbearing potential must be willing to practice birth control from the date of enrollment in this study until study follow-up.
Exclusion Criteria:
- severe hepatic and renal function abnormalities (alanine aminotransferase, bilirubin, creatinine > 2 times the upper limit of normal);
- Presence of organic heart disease with resulting clinical symptoms or abnormal cardiac function (NYHA cardiac function classification ≥ grade 2);
- ECG QTc interval >500 ms;
- active hepatitis B/hepatitis C;
- uncontrolled active infection;
- human immunodeficiency virus infection;
- concurrent other tumors requiring treatment or intervention;
- current or anticipated need for systemic corticosteroid therapy;
- pregnant or lactating women;
- abandonment of consolidation autologous hematopoietic stem cell transplantation for financial reasons;
- other psychological conditions that prevent the patient from participating in the study or signing the informed consent form;
- Subjects who, in the judgment of the investigator, are unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or do not meet the requirements for participation in the study.