CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* Histologically confirmed DLBCL and associated subtypes, defined by WHO 2016 classification: DLBCL not otherwise specified (NOS), High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (DHL/THL) and FL3B, T-cell/histocyte rich B-cell lymphoma, Primary mediastinal B-cell lymphoma, transformed lymphoma (transformed follicular) and R/R after at least 2 lines of systemic therapy
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG)/WHO performance status 0-2
* Secondary central nervous system (CNS) involvement is allowed however, then he/she must have

  \* No signs or symptoms of CNS involvement that would hamper adequate ICANS assessment
* Estimated life expectancy of \>3 months other than primary disease
* Patients of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen
* Signed and dated informed consent before conduct of any trial-specific procedure
* Patient is capable of giving informed consent

Exclusion Criteria:

* Absolute neutrophil count (ANC) \<1.0x10\^9/L
* Platelet count \<50x10\^9/L
* Absolute lymphocyte count \<0.1x10\^9/L
* Primary CNS lymphoma
* Known history of infection with hepatitis C or B virus unless treated and confirmed to be polymerase chain reaction (PCR) negative
* Active HIV infection with detectable viral load or CD4 T-cell count below 0.20x10\^9/L
* Known history or presence of seizure activities or on active anti- seizure medications within the previous 12 months
* Known history of CVA within prior 12 months
* Unstable neurological deficits
* Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis or other immunologic or inflammatory disease
* Active systemic autoimmune disease for which immunosupressive therapy is required
* Presence of CNS disease that, in the judgment of the investigator, may impair the ability to evaluate neurotoxicity, baseline dementia that would interfere with therapy or monitoring, determined using mini-mental status exam at baseline
* Active systemic fungal, viral or bacterial infection
* Clinical heart failure with New York Heart Association class ≥2 (appendix F) or Left Ventricular Ejection Fraction (LVEF) \<40%
* Resting oxygen saturation \<92% on room air
* Liver dysfunction as indicated by total bilirubin, AST and/or ALT \>5 x institutional ULN, unless directly attributable to the lymphoma or Gilbert disease
* GFR \<40 mL/min calculated according to the modified formula of Cockcroft and Gault or by direct urine collection
* Pregnant or breast-feeding woman
* Active other malignancy requiring treatment
* Medical condition requiring prolonged use of systemic immunosuppressives with exception of prednisolone \<10 mg/day
* History of severe immediate hypersensitivity reaction against any drug or its Ingredients/impurities that is scheduled to be given during trial participation e.g. as part of the mandatory lymphodepletion protocol, premedication for infusion, or rescue medication/salvage therapies for treatment related toxicities
* Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule

主要终点：Progression-free survival (PFS) from date of IMP infusion (if applicable) · PFS from date of IMP infusion is defined as the time from IMP infusion, until progression, relapse or death from any cause, whichever comes first. PFS reflects tumor growth and, therefore, occurs prior to the endpoint of OS. Progression is defined as the first date of documentation of a new lesion or enlargement of a previous lesion, or the date of the scheduled clinic visit immediately after radiologic assessment has been completed. If there is missing information, censoring of the data may be defined as the last date at which progression status was adequately assessed. · Approximately up to 60 months following first patient IMP infusion
次要终点：Progression-free survival (PFS) from date of randomization；Safety and toxicity assessment per AE reporting；Overall Response Rate (ORR)；Expansion of CAR T-cells；Phenotype of CAR T-cells；Persistence of CAR T-cells；Best Overall Response (BOR)；Duration Of Response (DOR)

• Arm A (ARI-0001) · EXPERIMENTAL · Infusion with Point of Care CAR T-cells
• Arm B (Axi-cel) · ACTIVE_COMPARATOR · Infusion with Standard of Care CAR T-cells

A phase II, multi-center study to compare the feasibility, and clinical efficacy of local manufacturing of CD19-directed CAR T-cells (ARI-0001 CAR T-cells) with commercial produced CAR T-cells (for example axicabtagene ciloleucel, a CD19 targeting commercially available CAR T-cell) in patients with relapsed or refractory (R/R) DLBCL.