This study is a single-arm, open-label, dose-escalation clinical trial to explore the safety, tolerability, pharmacokinetics and pharmacodynamics characteristics of the drug; The efficacy of the study drug in subjects with relapsed/refractory CD7-positive hematological malignancies, and the expression of B cells, T cells, and NK cell subtypes in peripheral blood were preliminarily observed. At the same time, explporing the distribution of anti-human CD7 CAR-NK cells in tumor tissues after administration of anti-human CD7 CAR-NK cell injection, and evaluating the immunogenicity of anti-human CD7 CAR-NK cell injection . To evaluate the correlation between the proportion of CD7-positive tumor cells and the safety and efficacy of anti-human CD7 CAR-NK cell injection and the evaluation. To explore the pharmacokinetics (PK) and pharmacodynamics(PD) characteristics of bone marrow in Chinese medicine.
"This study employed a dose escalation approach combining accelerated titration for the first dose group and the standard '3+3' rule for subsequent dose groups, aiming to minimize patient exposure to ineffective doses while reducing potential risks as much as possible. The study comprised three dose groups for single administration, with doses set at 1×10\^7 CAR-NK cells/kg, 2×10\^7 CAR-NK cells/kg, and 5×10\^7 CAR-NK cells/kg. For the 1×10\^7 CAR-NK cells/kg dose group, an accelerated titration method was applied: after obtaining informed consent, one eligible subject meeting the inclusion/exclusion criteria was enrolled into this group. A safety assessment was conducted 14-28 days after the first cell infusion. If no dose-limiting toxicity (DLT) occurred, the subject could proceed to the next dose group upon agreement between the investigator and sponsor. If DLT occurred in one subject, after evaluation by the investigator and sponsor, two additional subjects were enrolled into the same dose group for a 28-day observation period. If DLT events occurred in ≤1 of these three subjects, the study could advance to the next dose group; if DLT events occurred in \>1 subject, the decision to continue was made through joint discussion between the investigator and sponsor. Dose escalation to the 2×10\^7 CAR-NK cells/kg dose group followed the standard '3+3' rule. This group initially enrolled three subjects. If no DLT occurred in all three subjects, the study could proceed to the 5×10\^7 CAR-NK cells/kg dose group upon agreement between the investigator and sponsor. If one DLT occurred in this group, three additional subjects were enrolled for further observation of the same dose level. If the total number of DLT events among these six subjects was ≤1, the study could advance to the 5×10\^7 CAR-NK cells/kg dose group with agreement. If more than one subject experienced DLT in this group, enrollment for this dose level was terminated, and the dose was reduced to complete enrollment of remaining subjects, as decided by the investigator and sponsor. Dose escalation to the 5×10\^7 CAR-NK cells/kg dose group also adhered to the standard '3+3' rule. This group first enrolled three subjects. After cell infusion, a 28-day safety assessment was completed. If no DLT occurred in all three subjects, the decision to continue dose escalation was made through joint discussion between the investigator and sponsor. If no further escalation was decided, the remaining subjects were enrolled in this dose group. If one DLT occurred among the first three subjects, three additional subjects were enrolled for further observation. If DLT events occurred in \>1 of these six subjects, enrollment for this dose group was terminated, and the dose level was reduced to complete enrollment of remaining subjects. If no maximum tolerated dose (MTD) was observed at the maximum dose of 5×10\^7 CAR-NK cells/kg, the decision to add additional dose groups was made through joint discussion between the investigator and sponsor, with the new group still following the standard '3+3' rule. During the study, dose groups could be adjusted based on the tolerability, pharmacokinetics, pharmacodynamics, and efficacy of anti-human CD7 CAR-NK cells in patients, combined with prior CAR-NK treatment experience, as determined by the investigator and sponsor. This could involve adding or reducing groups or adjusting dose levels. If special safety or efficacy issues arose during dose escalation, the clinical study could be terminated after joint discussion between the investigator and sponsor.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Administer anti-human CD7 CAR-NK cell injection on D0
Shanghai General Hospital
Shanghai, Shanghai Municipality, China
Incidence of dose-limiting toxicity
To evaluate the incidence of DLT in patients with relapsed or refractory CD7-Positive Hematological Malignancies treated with anti-human CD7 CAR-NK cell injection, DLT is defined as any of the following events related to the study drug (including definitely related, probably related, and possibly related) that occurs within 14-28 days after the first dose of the investigational human CD7 CAR-NK cell injection (with appropriately extended observation duration for responders in dose groups showing therapeutic responses to assess whether DLT events resolve within the specified time frame), despite therapeutic interventions.
Time frame: Up to day 28
Incidence of adverse events
The occurence of study related adverse effects defined by NCI CTCAE5.0
Time frame: through study completion, an average of 2 year
Evaluate the number of CAR-NK cells in subjects' peripheral blood
Evaluate the number of Treg cells in subjects' peripheral blood after CD7 Car-NK cell injection administration
Time frame: Through study completion, an average of 2 year
Analysis of the number changes of cytokine in peripheral blood.
Analysis of the number changes of cytokine in peripheral blood,Levels of related cytokines (such as IL-6);
Time frame: Through study completion, an average of 2 year
Analysis of the number changes of lymphocyte subsets in peripheral blood.
Analysis of the number changes of lymphocyte subsets in peripheral blood, Including T/B/NK cells
Time frame: Through study completion, an average of 2 year
Objective Response Rate (ORR)
To evaluate the efficacy of CD7 Car-NK cell injection of relapsed or refractory CD7-Positive Hematological Malignancies subjects.
Time frame: Through study completion, an average of 2 year
Duration of response after administration (DOR)
Duration of response after administration (DOR),It refers to the time from the first assessment of CR or CRi or PR or MLFS to the first assessment of disease progression (Progressive Disease, PD) or death from any cause (including time post allogeneic hematopoietic stem cell transplantation).
Time frame: Through study completion, an average of 2 year
Progression-free survival post-administration
The time from cell infusion to the first assessment of tumor progression or death from any cause (including time post allogeneic hematopoietic stem cell transplantation).
Time frame: Through study completion, an average of 2 year
Overall survival
The time from the start of cell reinfusion to death due to any cause. For subjects who have dropped out before death, the last follow-up time will be recorded as the time of death.
Time frame: Through study completion, an average of 2 year
jiahua niu, Master
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