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

A Single-Arm, Multicenter, Open-Label Clinical Study to Evaluate the Efficacy and Safety of Axicabtagene Ciloleucel Injection as First-Line Therapy of High-Risk Large B-Cell Lymphoma

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.

Study Overview

• Status: Not yet recruiting
• Conditions: High-risk Large B-cell Lymphoma (LBCL); CAR-T Cell Therapy
• Intervention / Treatment: Drug: Axicabtagene Ciloleucel

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Weili Zhao M.D. and Ph.D; Phone Number: +862164370045 ext 610707; Email: zwl_trial@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • China

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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.
• History of clinically significant cardiac disease within 12 months prior to enrollment.
• Any other condition deemed by the investigator as unsuitable for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Participant Group; 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; A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells; Other Names: Axi-cel; FKC-876

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Metabolic Response (CMR) - determined by investigator	CMR from axi-cel infusion (without additional anticancer therapy) based on investigator disease assessment according to PET-scan (using the Lugano Response Criteria)	3 months from axi-cel infusion
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAE)	An AE was any untoward medical occurrence in a participant in a clinical trial participant, which did not necessarily have a causal relationship with the treatment. Treatment-emergent adverse events were defined as any adverse event with onset on or after the axicabtagene ciloleucel infusion. Serious adverse event was defined as an event that resulted in the following: death; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital anomaly or birth defect; and medically important event or reaction.	Up to 2 years
Objective Response Rate (ORR) Per the Lugano Classification as Determined by Study Investigators	ORR: percentage of participants with CR (CMR;CRR) or PR (partial metabolic response (PMR); partial radiologic response (PRR)). CMR: PET 5PS scores of 1 (no uptake above background, 2 (uptake ≤mediastinum), 3 (uptake >mediastinum but ≤liver) with/without a residual mass; no new lesions; no evidence of FDG-avid disease in BM. CRR: target nodes/nodal masses regressed to ≤1.5 cm in LDi; no extralymphatic sites of disease; absent NMLs; organ enlargement regress to normal; no new sites; bone marrow morphology normal. PMR: scores 4 (uptake moderately >liver),5 (uptake markedly >liver, new lesions) with reduced uptake compared with baseline and residual mass; no new lesions; responding disease at interim/residual disease at end of treatment (EOT). PRR: ≥50% decrease in sum of the product of perpendicular diameters (SPD) of up to 6 target measurable nodes and extra-nodal sites; absent/normal, regressed, but no increase of NMLs; spleen regressed by >50% in length beyond normal; no new sites.	Up to 2 years
Duration of Response (DOR) Per the Lugano Classification	DOR is defined only for participants who experience an objective response after axicabtagene ciloleucel infusion and is the time from the first objective response to disease progression (PD) (Lugano classification) or death from any cause. Objective response is defined in outcome measure (OM) 2. PD is defined as a score 4 (uptake moderately > liver) or 5 (uptake markedly >liver and/or new lesions) with an increase in intensity of uptake from baseline; new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment; new FDG-avid foci consistent with lymphoma rather than another etiology (eg, infection, inflammation); new or recurrent FDG-avid foci in bone marrow. Kaplan-Meier (KM) estimates were used for analysis.	Up to 2 years
Progression-Free Survival (PFS)	PFS was defined as the time from axicabtagene ciloleucel infusion date to the date of disease progression per Lugano classification or death from any cause.	Up to 2 years
Overall Survival (OS)	OS is defined as the time from axicabtagene ciloleucel infusion to the date of death from any cause.	Up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8	Peak is defined as the maximum post-baseline level of cytokine from baseline to Week 4.	Up to Week 4
Peak Serum Level of C-Reactive Protein (CRP)	Peak is defined as the maximum post-baseline level of cytokine from baseline to Week 4.	Up to Week 4
Peak Serum Level of Ferritin	Peak is defined as the maximum post-baseline level of cytokine from baseline to Week 4	Up to Week 4
Proportion of participants experiencing a clinically meaningful improvement in physical functioning and fatigue (EORTC QLQ-C30)		Up to 2 years

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2025
• Primary Completion (Estimated): October 9, 2026
• Study Completion (Estimated): April 9, 2028

Study Registration Dates

• First Submitted: April 11, 2025
• First Submitted That Met QC Criteria: April 11, 2025
• First Posted (Actual): April 20, 2025

Study Record Updates

• Last Update Posted (Actual): April 22, 2025
• Last Update Submitted That Met QC Criteria: April 21, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: LBCL; axi-cel; car-t
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Antineoplastic Agents, Immunological; Antineoplastic Agents; Axicabtagene ciloleucel
• Other Study ID Numbers: RJ-1L HR-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No