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.
Aged 1-12 years with weight≥10kg, male or female;
The child and/or guardian has signed the informed consent form (ICF) and has the ability to comply with the study requirements.
Relapsed neuroblastoma: New lesions appear at the primary site or other locations 4 weeks after achieving complete remission through first-line standard treatment.
Refractory neuroblastoma: Failure to achieve complete remission after standard treatment protocols, which include induction chemotherapy, surgery, and radiotherapy targeting the primary tumor and residual metastatic sites;
Suffering from malignant tumors or diagnosed within 5 years before enrollment, excluding radical skin basal cell carcinoma, skin squamous cell carcinoma, thyroid cancer, breast cancer (ductal carcinoma in situ) and / or radical resection of carcinoma in situ.
Participants with symptomatic central nervous system (CNS) metastasis confirmed by imaging or pathological examination.
Participants with MIBG non-avid disease.
Participants with a history of organ transplantation（excluding stem cell transplantation）;
Single group
Chimeric Natural Killer Receptor Universal T-cells (CNK-UT)
DrugOUTLINE: 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.
Incidence 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
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.
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.
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 (%).
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.
biomarkers
Ferritin, lactate dehydrogenase (LDH), neuron specific enolase (NSE) will be analyzed.
Levels of peripheral blood lymphocyte subsets
Percentage of T cell、B cell、NK Cells、Treg cell and MDSC in peripheral blood detected by FCM after infusion.
Click on the lead sponsor to view all of their trials.
Nanjing Children's Hospital
Lead sponsor
Nanjing Medical University
Sponsor institution
