This is a single arm, open-label, multi-center, pilot studies (Investigator Initiated Trial, IIT) to evaluate the safety, preliminary efficacy, pharmacokinetics of universal T-cells engineered with chimeric natural killer receptor (CNK-UT) to treat the patients with relapsed/refractory Neuroblastoma.
This is a single arm, open-label, phase I, dose escalation/dose expansion study to assess the safety of CNK-UT cells therapy, and to obtain the preliminary efficacy and pharmacokinetics result in participants who have been diagnosed with relapsed/refractory Neuroblastoma.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
OUTLINE: This is a dose-escalation study of CNK-UT cells followed by a dose-expansion study. 1. Dose Escalation (Single Ascending Dose Study, SAD): During SAD study stage, the participants will be intravenous infused with CNK-UT cells (3\~34×10\^7 CNK+ cells/kg)with a"3 +3" design to determine the maximum tolerated dose. During single ascending dose (SAD) study stage, the participants will receive a single dose of CNK-UT cells before the DLT observation period (21 days). If the participants do not experience DLT, they will be able to enter a multiple ascending dose (MAD) study stage. 2. Dose Expansion (multiple ascending dose study, MAD): During MAD study stage, the participants will receive multiple doses of CNK-UT cells. The dosage and frequency of drug administration in the dose expansion stage can be adjusted and determined according to the SAD study.
Nanjing Children's Hospital
Nanjing, Jiangsu, China
RECRUITINGNanjing
Nanjing, Jiangsu, China
RECRUITINGIncidence of Treatment Related adverse events (AEs)
Incidence of Treatment Related AEs, AEs of special interest and serious adverse events (SAEs) assessed by NCI-CTCAE v5.0 criteria
Time frame: up to 1 year
Objective Response Rate (ORR)
Overall response is defined as either a complete or partial response (CR+PR), the response should be confirmed no less than 4 weeks after the first evaluation.
Time frame: up to 1 year
Duration of Response (DOR)
The period from the first evaluation of CR or PR to the first evaluation of PD or death of any cause.
Time frame: up to 1 year
Disease control rate (DCR)
The number of cases in which response are achieved from the start of cells infusion/the total number of evaluable cases (%).
Time frame: up to 1 year
Progression-free Survival (PFS)
The period from the day when the participant receives the cell therapy to the first recorded disease progression (whether treated or not) or death of any cause, which occurs first.
Time frame: up to 1 year
Overall survival (OS)
The period from the first infusion to any cause of death.
Time frame: up to 1 year
Pharmacokinetics (PK) (Cmax)
The Peak Plasma concentration (Cmax) of amplified CNK-UT DNA in peripheral blood after infusion.
Time frame: up to 1 year
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Pharmacokinetics (PK) (Tmax)
The time to reach the maximum concentration (Tmax).
Time frame: up to 1 year