CAR-T Combined With ASCT in the Treatment of Relapsed/Refractory Large B-cell Lymphoma With High-risk Factors.

Official title

A Single-arm, Single-center, Open-label Clinical Study on the Efficacy and Safety of CAR-T Combined With ASCT in the Treatment of Relapsed/Refractory Large B-cell Lymphoma With High-risk Factors.

Overview

This is a prospective, single-arm, single-center, open-label clinical study, aiming to evaluate the efficacy and safety of CAR-T combined with ASCT in the treatment of relapsed/refractory large B-cell lymphoma with high-risk factors.

Detailed description

R/R LBCL with high-risk factors sequentially undergo leukapheresis, stem cell collection, bridging therapy (if applicable, at the investigator's discretion, with only one course of bridging therapy allowed), preconditioning chemotherapy phase (for CNSL patients: TB regimen, carmustine 300 mg/m² on Day -6, thiotepa 10 mg/kg on Day -5 to Day -4; for non-CNSL patients: BEAM regimen, carmustine 300 mg/m² on Day -7, etoposide 150 mg/m² on Day -6 to Day -3, cytarabine 200 mg/m² on Day -6 to Day -3, melphalan 140 mg/m² on Day -2; for patients with prior autologous hematopoietic stem cell transplantation, the investigator may develop other preconditioning regimens based on factors such as the patient's drug sensitivity and tolerability), stem cell infusion (Day 0), and CAR-T cell infusion (Day 4 to Day 7).

Interventions

• Biological Axicabtagene Ciloleucel
  R/R LBCL with high-risk factors sequentially undergo leukapheresis, stem cell collection, bridging therapy (if applicable, at the investigator's discretion, with only one course of bridging therapy allowed), preconditioning chemotherapy phase (for CNSL patients: TB regimen, carmustine 300 mg/m² on Day -6, thiotepa 10 mg/kg on Day -5 to Day -4; for non-CNSL patients: BEAM regimen, carmustine 300 mg/m² on Day -7, etoposide 150 mg/m² on Day -6 to Day -3, cytarabine 200 mg/m² on Day -6 to Day -3, me

Primary outcome measures

• 1-year PFS rate [Time frame: From date of CAR-T infusion until the date of first documented date of disease progression or death from any cause, assessed up to 12 months]

Secondary outcome measures (5)

• bORR [Time frame: The best therapeutic effect within 12 months after CAR-T infusion was the proportion of subjects achieving complete remission (CR) or partial remission (PR).]
• DOR [Time frame: 12 months after CAR-T infusion]
• PFS [Time frame: From date of CAR-T infusion until the date of first documented date of disease progression or death from any cause, assessed up to 12 months]
• OS [Time frame: From date of CAR-T infusion until the date of first documented date of death from any cause, assessed up to 12 months]
• AE and SAE [Time frame: All adverse events that occurred from the time of enrollment to 12 months after the CAR-T infusion]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Histopathologically confirmed large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL), central nervous system lymphoma (CNSL), primary mediastinal large B-cell lymphoma (PMBCL), and transformed follicular lymphoma (tFL)
• Must have received first-line treatment with a regimen containing anti-CD20 monoclonal antibody and anthracycline
• Meet one of the following clinical high-risk factors or molecular biological high-risk factors:

• Clinical high-risk factors: Failure to achieve partial response (PR) after 4 cycles of first-line immunochemotherapy; or relapse within 12 months after achieving complete response (CR) with first-line immunochemotherapy; or relapse after autologous hematopoietic stem cell transplantation (ASCT); or central nervous system involvement at the time of disease relapse or progression
• Molecular biological high-risk factors: TP53 gene mutation; or high-grade B-cell lymphoma (HGBL) with MYC and Bcl-2 rearrangements, with or without Bcl-6 rearrangement
• ECOG 0 to 2
• Eligible for high-dose chemotherapy/autologous hematopoietic stem cell transplantation (HDCT/ASCT) per the investigator's assessment, and planned to receive a sequential regimen of ASCT followed by CAR-T therapy
• Hepatic and renal function meet the following criteria: Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN); total bilirubin ≤ 1.5 mg/dL; serum creatinine ≤ 1.5 × ULN, or creatinine clearance (calculated using the Cockcroft-Gault formula) ≥ 30 mL/min
• Left ventricular ejection fraction (LVEF) ≥ 40%
• Life expectancy ≥ 3 months

Exclusion criteria

• Patients who have previously received any CD19-targeted therapy
• Patients with CD19 negativity confirmed by immunohistochemistry (IHC)
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, defined as HBV DNA or HCV RNA level above the upper limit of normal (ULN), with or without liver function abnormalities
• Presence of uncontrolled infection, cardio-cerebrovascular diseases, coagulopathy, or connective tissue diseases
• History of human immunodeficiency virus (HIV) infection
• Pregnant or lactating patients

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

• Zhejiang Cancer Hospital — Hangzhou

Identifiers

NCT: NCT07538635 · CAR-T+ASCT · No ID

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗