To evaluate the safety and tolerability of CD19-CAR-DNT cells infusion in subjects with relapsed/refractory B-cell non-Hodgkin's Lymphoma
This is an open, single-arm, single-dose, dose-escalation and dose-expansion clinical trial designed to evaluate the maximum tolerated dose of CD19-CAR-DNT cells, the safety, the preliminary efficacy and the pharmacokinetic profile of CD19-CAR-DNT cells in vivo after infusion in clinical studies. 9 patients are planned to be enrolled in the dose-escalation trial (1×10\^6 CD19-CAR-DNT cells/kg, 3×10\^6 CD19-CAR-DNT cells/kg, 9×10\^6 CD19-CAR-DNT cells/kg) and 3 patients in the dose-expansion trial. The primary endpoints are DLT, MTD, and the incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Lentiviral vector-transducted DNT cells to express anti-CD19 CAR. Prior to cellular infusion, each patient received cyclophosphamide and fludarabine lymphodepleting chemotherapy.
2nd Affiliated Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang, China
RECRUITINGDLT
To evaluate the safety, tolerability, and determine the recommended dosage of CD19-CAR-DNT Cell Therapy for Relapsed/Refractory B-cell Non-Hodgkin Lymphoma
Time frame: Up to 28 days
MTD
MTD was the highest dose for DLT in ≤1/6 subjects
Time frame: Up to 28 days
Incidence of abnormalities
Incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs.
Time frame: Up to 28 days
Pharmacokinetics (PK) indicator (Cmax)
The peak concentration of CD19-CAR-DNT cells amplified in the peripheral blood (Cmax, detected by qPCR).
Time frame: Up to 90 days
Pharmacokinetics (PK) indicator (AUC)
CD19-CAR-DNT cells blood concentrations will be measured at different time points to evaluate the area under the curve (AUC). (AUC, detected by qPCR).
Time frame: Up to 90 days
Pharmacokinetics (PK) indicator (Tmax)
CD19-CAR-DNT cells blood concentrations will be measured at different time points to evaluate the peak plasma time (Tmax). Tmax is defined as the time to reach the highest concentration (Tmax, detected by qPCR).
Time frame: Up to 90 days
Pharmacokinetics (PK) indicator (T1/2)
CD19-CAR-DNT cells blood concentrations will be measured at different time points to evaluate the elimination half-life in hours (T1/2). T1/2 is defined as the time point when the concentration of CD19-CAR-DNT reaches half of maximum in a patient's peripheral blood (T1/2, detected by qPCR).
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Time frame: Up to 90 days
Overall Response Rate
The proportion of CR or PR patients as assessed by investigators based on Lugano 2014 Response Assessment
Time frame: Up to 2 years
Disease Control Rate
The percentage of PR, CR and SD patients in the total patient population
Time frame: Up to 2 years
Duration of Response
The time from the start of the first assessment of CR or PR to the first assessment as disease recurrence or progression or death
Time frame: Up to 2 years
Progression Free Survival
The length of time that a participant's disease did not progress during or after CD19-CAR-DNT treatment.
Time frame: Up to 2 years
Overall Survival
From the date of entry into the clinical study until death from any cause
Time frame: Up to 15 years