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.
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 .
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
20
1. RT regimen: localized low dose RT: 1-1.5Gy/fraction\*5fractions 2. Reduced dose SEAM regimen (CNS uninvolved): * Simustine 250mg/m2 d-6 orally * Cytarabine 200mg/m2 q12h d-5\~d-4 intravenous infusion * Etoposide 100mg/m2 q12h d-5\~d-4 intravenous infusion * Melphalan 140mg/m2 q12h d-3 intravenous infusion 3. TB regimen (CNS involvement): * Thiotepa 250mg/m2 qd, d-8\~d-6 intravenous infusion * Busulfan 0.8mg/kg q6h d-5\~d-3 intravenous infusion
1. RT regimen: localized high dose RT: 3-6Gy/fraction\*5fractions 2. Reduced dose SEAM regimen (CNS uninvolved): * Simustine 250mg/m2 d-6 orally * Cytarabine 200mg/m2 q12h d-5\~d-4 intravenous infusion * Etoposide 100mg/m2 q12h d-5\~d-4 intravenous infusion * Melphalan 140mg/m2 q12h d-3 intravenous infusion 3. TB regimen (CNS involvement): * Thiotepa 250mg/m2 qd, d-8\~d-6 intravenous infusion * Busulfan 0.8mg/kg q6h d-5\~d-3 intravenous infusion
the First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China
RECRUITINGComplete remission rate(CRR)
The rate of patients who achieved CR 3 months after CAR-T infusion
Time frame: At the end of 3 months after CAR-T infusion
Major adverse reactions
The safety and tolerability of the therapeutic regimen measured by the major adverse events.
Time frame: From enrollment to 1 month after CAR-T infusion of last patient
Time to bone marrow hematopoietic reconstitution
The time of bone marrow hematopoietic reconstitution after stem cell infusion
Time frame: From enrollment to 3 months after stem cell infusion of last patient
2-year progression-free survival(PFS)
PFS will be assessed from the first date of radiotherapy to the progression of the disease, death, or last follow-up.
Time frame: From enrollment to 2-year after the end of last patient's treatment
2-year overall survival(OS)
OS will be assessed from the first date of radiotherapy to death from any cause or last follow-up
Time frame: From enrollment to 2-year after the end of last patient's treatment
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