Clinical trial NCT06935136: Study to Evaluate the Efficacy and Safety of Axicabtagene Ciloleucel Injection as First-Line Therapy of High-Risk Large B-Cell Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: CAR-T Cell Therapy
High-risk Large B-cell Lymphoma (LBCL)
Keywords: axi-cel
car-t
LBCL
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2025-04-20
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Complete Response (CR) Rate Per the Lugano Classification as Determined by Study Investigators
timeFrame: Up to 2 years
Secondary outcomes:
measure: Objective Response Rate (ORR) Per the Lugano Classification as Determined by Study Investigators
timeFrame: Up to 2 years
measure: Complete Metabolic Response (CMR) - determined by investigator
timeFrame: 3 months from axi-cel infusion
measure: Duration of Response (DOR) Per the Lugano Classification
timeFrame: Up to 2 years
measure: Progression-Free Survival (PFS)
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 2 years
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAE)
timeFrame: Up to 2 years
Other outcomes:
measure: Peak Serum Level of Granzyme B, Interferon-gamma (IFNg), Interleukin (IL)-2, IL-5, IL-6, IL-8
timeFrame: Up to Week 4
measure: Peak Serum Level of C-Reactive Protein (CRP)
timeFrame: Up to Week 4
measure: Peak Serum Level of Ferritin
timeFrame: Up to Week 4
measure: Proportion of participants experiencing a clinically meaningful improvement in physical functioning and fatigue (EORTC QLQ-C30)
timeFrame: Up to 2 years
Locations:
city: Shanghai
country: China
facility: China
state: Shanghai
Study officials:
References: