Study to Evaluate the Efficacy and Safety of Axicabtagene Ciloleucel Injection as First-Line Therapy of High-Risk Large B-Cell Lymphoma

NCT06935136 | Not Yet Recruiting

• 1 other identifier: RJ-1L HR-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this is Single-Arm, Multicenter, Open-Label Clinical Study is to Evaluate the Efficacy and Safety of Axicabtagene Ciloleucel Injection(Axi-cel) as First-Line Therapy of High-Risk Large B-Cell Lymphoma.

Conditions

CAR-T Cell Therapy; High-risk Large B-cell Lymphoma (LBCL)

Keywords

axi-cel; car-t; LBCL

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators

  CR Rate is the percentage of participants with CR (complete metabolic response (CMR); complete radiological response (CRR)). CMR: positron emission tomography (PET) 5-point scale (5-PS) scores of 1 (no uptake above background), 2 (uptake ≤ mediastinum), 3 (uptake \> mediastinum but ≤ liver) with/without a residual mass); no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow (BM). CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in longest transverse diameter of lesion (LDi); no extralymphatic sites of disease; absent non-measured lesion (NMLs); organ enlargement regress to normal; no new sites; and bone marrow normal by morphology.

  Up to 2 years

Secondary Outcomes (6)

• Objective Response Rate (ORR) Per the Lugano Classification as Determined by Study Investigators

  Up to 2 years

• Complete Metabolic Response (CMR) - determined by investigator

  3 months from axi-cel infusion

• Duration of Response (DOR) Per the Lugano Classification

  Up to 2 years

• Progression-Free Survival (PFS)

  Up to 2 years

• Overall Survival (OS)

  Up to 2 years

Other Outcomes (4)

• Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8

  Up to Week 4

• Peak Serum Level of C-Reactive Protein (CRP)

  Up to Week 4

• Peak Serum Level of Ferritin

  Up to Week 4

Study Arms (1)

Participant Group

EXPERIMENTAL

Participants will receive cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV conditioning chemotherapy for 3 days followed by axicabtagene ciloleucel（Axi-cel） administered as a single IV infusion at a target dose of 2 x 10\^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0.

Drug: Axicabtagene Ciloleucel

Interventions

Axicabtagene Ciloleucel DRUG

A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells

Also known as: FKC-876, Axi-cel

Participant Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed LBCL (Large B-Cell Lymphoma) according to the WHO 2016 classification, including the following subtypes:DLBCL-NOS (Diffuse Large B-Cell Lymphoma, Not Otherwise Specified),HGBL (High-Grade B-Cell Lymphoma, including HGBL with MYC, BCL-2, and/or BCL-6 rearrangements (DHL/THL), HGBL-NOS),DLBCL transformed from follicular or marginal zone lymphoma, eligible if the patient has not previously received anthracycline-containing therapy
• International Prognostic Index (IPI) score of 2-5 at initial diagnosis.
• Individuals must have a positive interim positron emission tomography (PET) (Deauville PET score of 4 or 5) after 2 cycles (PET2+) of chemoimmunotherapy or high-risk ctDNA status (ctDNA levels not reduced by at least 2-log after two cycles of R-chemotherapy)
• Age of 18 years or older.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
• Adequate renal, hepatic, pulmonary, and cardiac function, defined as:
• Creatinine clearance (estimated by Cockcroft-Gault formula) ≥ 60 mL/min
• Serum ALT/AST ≤ 2.5 × Upper Limit of Normal (ULN)
• Total bilirubin ≤ 1.5 × ULN (except for patients with Gilbert's syndrome)
• Left ventricular ejection fraction ≥ 50%, no pericardial effusion as determined by echocardiography, and no clinically significant arrhythmias No clinically significant pleural effusion
• Baseline peripheral oxygen saturation \> 92% under room air ventilation
• At least one measurable lesion.
• For women of childbearing potential, a negative serum pregnancy test is required (women who have undergone surgical sterilization or are postmenopausal for at least 2 years are considered not to be of childbearing potential).

You may not qualify if:

• According to the WHO 2016 classification, patients with the following subtypes are excluded:
• LBCL with T-cell/histiocyte-rich background
• Primary central nervous system DLBCL
• PMBCL (Primary Mediastinal B-Cell Lymphoma)
• B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical HL (Hodgkin Lymphoma)
• Burkitt lymphoma
• History of Richter transformation in chronic lymphocytic leukemia
• Presence of detectable malignant cells in the CSF (cerebrospinal fluid), brain metastases, or history of central nervous system involvement by lymphoma.
• Presence of cardiac involvement by lymphoma.
• Prior treatment for LBCL other than two cycles of R-chemotherapy.
• History of severe immediate hypersensitivity reaction to any of the drugs used in this study.
• Presence of central nervous system disorders: history of stroke, transient ischemic attack, or reversible posterior leukoencephalopathy syndrome (PRES) within 12 months prior to enrollment.
• History of acute or chronic active hepatitis B or C infection, unless HBV-DNA and HCV-RNA levels are below the level of detection.
• Human immunodeficiency virus (HIV) positivity, unless on appropriate antiretroviral therapy with undetectable viral load by PCR and a CD4 count \> 200 cells/µL.
• Any medical condition that may interfere with the assessment of the safety or efficacy of the study treatment.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

China

Shanghai, Shanghai Municipality, 200025, China

Location

MeSH Terms

Interventions

axicabtagene ciloleucel

Central Study Contacts

Weili Zhao M.D. and Ph.D

CONTACT

+862164370045 ext 610707; zwl_trial@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ruijin Hospital

Study Record Dates

• First Submitted: April 11, 2025
• First Posted: April 20, 2025
• Study Start: April 30, 2025
• Primary Completion (Estimated): October 9, 2026
• Study Completion (Estimated): April 9, 2028
• Last Updated: April 22, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)