CAR-T Following ASCT for Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (R/R B-NHL) With High-Risk Prognostic Factors

Official title

A Single-Arm Clinical Study of CD19 CAR-T Following ASCT for Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (R/R B-NHL) With High-Risk Prognostic Factors

Overview

Clinical trial for the safety and efficacy of CD19 CAR-T following autologous hematopoietic stem cell transplantation (ASCT) for Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (R/R B-NHL) with High-Risk Prognostic Factors

Detailed description

This is a single-center, single-arm, open-label, prospective clinical trial to evaluate the efficacy and safety of CD19 CAR-T infusion following high-dose chemotherapy and autologous stem-cell transplantation (HDT/ASCT) in relapsed or refractory B-cell Non-Hodgkin's Lymphoma patients with high-risk prognostic factors (extranodal involvement/bulky mass ≥5 cm in diameter/TP53 alterations). CD19 CAR-T will be infused on day +3 (±1d) with a fixed dose of 100X10\^6. The study will assess the safety and efficacy of this combinational therapy, including the investigators assessed the best complete response rate (BCR) in 3 months (primary endpoint), objective response rates, survivals, incidence and severity of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematological, and other non-hematological toxicities of the subjects.

Interventions

• Other autologous stem-cell transplantation
  high-dose chemotherapy and autologous stem-cell transplantation (HDT/ASCT)
• Drug Relmacabtagene autoleucel (relma-cel)
  relma-cel (CD19 CAR-T cell)infusion on day 3(±1d) after ASCT with a fixed dose of 100X10\^6.

Primary outcome measures

• Best Complete Response (CR) Rate in 3 months [Time frame: 3months post CAR-T infusion]

Secondary outcome measures (5)

• Objective remission rate (ORR) in 3months [Time frame: 3months post CAR-T infusion]
• Duration of Response (DOR) [Time frame: 2 years post CAR-T infusion]
• Progression-Free Survival (PFS) [Time frame: 2 years post CAR-T infusion]
• Overall Survival (OS) [Time frame: 2 years post CAR-T infusion]
• Adverse Events rate as assessed by CTCAE version 5.0 [Time frame: 2 years post CAR-T infusion]

Eligibility criteria

Inclusion criteria

• Histologically confirmed B-cell non-Hodgkin's lymphoma including the following types

• diffuse large B-cell lymphoma
• high-grade B-cell lymphoma with or without MYC and BLC2 and/or BCL6 rearrangement
• transformed lymphoma
• primary mediastinal large B-cell lymphoma
• follicular lymphoma (FL)
• Relapsed or refractory diseases fulfilling one of the following criteria (individuals must have received anti-CD20 monoclonal antibody and anthracycline-containing chemotherapy regimen)

• Primary refractory disease, defined as disease progression after first-line immunochemotherapy or disease progression within 6 weeks of the end of the last chemotherapy
• Stable disease (SD) as best response after at least 4 cycles of first-line therapy
• Partial response (PR) as best response after at least 6 cycles of first-line therapy (biopsy-proven residual disease is needed for individuals with Deauville score of 4)
• PR as best response after at least 2 cycles of second-line therapy
• Disease relapse ≤12 months after the completion of first-line immunochemotherapy
• Relapsed or refractory disease after ≥2 lines of chemotherapy
• Presence of at least one of the following high-risk prognostic factors: (1) extranodal involvement; (2) maximum diameter of the bulky mass ≥5 cm; (3) TP53 gene alterations
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Eligible for HDCT/ASCT based on the investigator's assessment and are scheduled to undergo an ASCT sequential CAR-T treatment regimen
• Adequate renal and hepatic function defined as:

• Serum alanine aminotransferase (ALT/AST) ≤ 3 upper limit of normal (ULN)
• Total bilirubin ≤1.5 mg/dL(<3 times ULN in patients with Gilbert's syndrome, cholestasis due to hepatoportal compression adenopathy, biliary obstruction in patients with liver involvement or lymphoma)
• Serum creatinine ≤1.5 ULN, or creatinine clearance (as estimated by Cockcroft Gault) ≥ 30 mL/min
• Cardiac ejection fraction ≥ 40%
• Baseline oxygen saturation > 95% on room air
• Life expectancy ≥3 months

Exclusion criteria

• History of autologous or allogeneic stem cell transplantation
• Active HBV or HCV infection, defined as HBV-DNA or HCV-DNA levels above the normal upper limit, with or without abnormal liver function. Individuals with positive HBsAg or HBcAb should receive antiviral prophylaxis for at least 12 months after CAR-T cells infusion.
• Presence of uncontrolled infection, cardio-cerebrovascular disease，coagulopathy, or connective tissue disease.
• History of HIV infection
• Prior chimeric antigen receptor cellular immunotherapy targeting CD19
• 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

• Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai

Identifiers

NCT: NCT06365671 · ASCT-CART

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗