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

Shanghai Jiao Tong University

Status: Not yet enrolling

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

Treatments: Drug: Axicabtagene Ciloleucel

Study type: Interventional

Funder types: Other

Identifiers

NCT06935136

RJ-1L HR-01

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

60 participants in 1 patient group

Participant Group

Experimental group

Description:

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.

Treatment:

Drug: Axicabtagene Ciloleucel