Objective: To evaluate the safety and tolerability of hNeo-T injection in patients with relapsed or refractory EBV-positive T-cell lymphoma. Secondary objective: To evaluate the effectiveness of hNeo-T injection, and to evaluate the objective response rate (ORR) and disease control rate (DCR) by Lugano2014 criteria; Progression-free survival (PFS), duration of response (DOR), and overall survival (OS ) followed. Objective of the exploratory study: To investigate the in vivo process of hNeo-T injection and describe the activity and related biological functions of hNeo-T cells in vivo, including but not limited to.
This is a single arm,open label and non-randomized clinical trial with a planned enrollment of 6-12 participants to evaluate the safety and tolerability of hNeo-T injection, determine dose-limiting toxicity (DLT), explore the maximum tolerated dose (MTD), or the recommended dosage for later clinical studies. The DLT observation period is 28 days after the infusion of hNeo-T injection. In the first stage, 3 subjects will be enrolled in the experiment of the first dose group (total number of cells is 5×10\^7/ bag). If DLT does not appear during the experiment, the study will enter the second stage after safety assessment and analysis, and 3 subjects will be enrolled in the experiment of the second dose group (total number of cells is 1×10\^8/ bag) in this stage. If DLT occurs in one of the 3 subjects , three more subjects will be added to the dose group. If no additional DLT occurs, the study will enter the next dose group; If additional DLT occurs, enrollment in the group will be stopped and the dose will be defined as an intolerable dose; If DLT occurs in two or more of the 3 subjects, enrollment in the dose group will be discontinued and the dose will be defined as an intolerable dose; After climbing to an intolerable dose, there will be a discussion to decide whether to explore an intermediate dose or to define the dose level as MTD; If MTD is not defined in the high-dose group, the high-dose group will be used as the final climbing dose. If a higher dose will be planned, a follow-up clinical study can only be carried out after evaluation,discussion and consensus.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
After subject screening, peripheral blood mononuclear cell (PBMC) donors matching half or more of the subject's HLA matching will undergo blood collection to prepare hNeo-T. hNeo-T preparation is expected to be 25-30 days after blood collection. In this study, the bridging therapy will be allowed before Chemotherapy preconditioning, and the investigators will decide whether to use it. Chemotherapy preconditioning will be performed before hNeo-T transfusion. If the absolute value of lymphocyte (LYM) before pretreatment is \<0.8×10\^9/L and the subject meets the criteria for cell transfusion, the chemotherapy preconditioning will not be performed and subsequent cell transfusion can be performed directly.
Chemotherapy preconditioning will be performed before hNeo-T transfusion.
Chemotherapy preconditioning will be performed before hNeo-T transfusion
ShenZhen University General Hospital
Shenzhen, Guangdong, China
RECRUITINGSafety assessment (Evaluation of treatment-related adverse events according to CTCAEv5.0)
To determine the incidence of AE and SAE in clinical trials
Time frame: The first dose will be administered until 28 days after the last dose
Objective response rate (ORR)
The total number of subjects with complete response (CR) and partial response (PR) confirmed according to Lugano2014 criteria (i.e., CR+PR) and the proportion of subjects in the corresponding analysis set
Time frame: Up to 48 weeks
Disease control rate (DCR)
The total number of subjects with CR, PR, and stable disease (SD) confirmed according to Lugano2014 criteria (i.e. CR+PR+SD) and the proportion of subjects in the corresponding analysis set
Time frame: Up to 48 weeks
Progression free survival (PFS)
According to the Lugano2014 criteria, the time between the start of cell transfusion and the first recorded date of disease progression (PD) or death. If no disease progression is observed, the deletion date should be the date of the last tumor measurement, and if there is no baseline and/or tumor evaluation after transfusion, the PFS will be deleted to the cell transfusion date. Detailed rules on deletion will be described in the statistical analysis plan.
Time frame: Up to 52 weeks
Duration of response (DOR)
According to the Lugano2014 criteria, the time between a subject's first identification with CR or PR and the first recording of PD or the date of death, depending on which occurs first. For subjects who do not experience disease progression after a combined response, the duration of response will be deleted at the last evaluable tumor measurement date.
Time frame: Up to 36 weeks
Overall survival (OS)
The time from cell transfusion to death who have completed the prescribed dose. If the subjects is lost to follow-up, the last known date of survival will be OS deletion time.
Time frame: Up to 72 weeks
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