study to evaluate the efficacy and safety of axicabtagene ciloleucel injection as first-line therapy of high-risk large b-cell lymphoma

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

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.

Keywords: axi-cel car-t lbcl