This is a single arm, open-label, multi-center, pilot studies (Investigator Initiated Trial, IIT) to evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of universal T-cells engineered with chimeric natural killer receptor (CNK-UT) to treat the patients with steroid-refractory/resistant or steroid-dependent aGVHD.
This is a single arm, open-label, multi-center, pilot studies (Investigator Initiated Trial, IIT) to evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of universal T-cells engineered with chimeric natural killer receptor (CNK-UT) to treat the patients with steroid-refractory/resistant or steroid-dependent acute graft-versus-host disease (aGvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
23
Dose Escalation (Single Ascending Dose Study, SAD): During SAD study stage, the participants will be intravenous infused with CNK-UT cells (3×10\^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. Dose Expansion (multiple ascending dose study, MAD): During MAD study stage, the participants will receive multiple doses of CNK-UT cells(6-10×10\^7 CNK+ cells/kg). The dosage and frequency of drug administration in the dose expansion stage can be adjusted and determined according to the SAD study.
First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, China
RECRUITINGThe first affiliated hospital of zhejiang university, school of medicine.
Hangzhou, Zhejiang, 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
Identification of Maximum Tolerated Dose (MTD) & incidence of Dose-limiting Toxicities (DLTs)
Incidence of dose-limiting toxicities (DLTs)
Time frame: up to 21 days since first infusion of CNK-UT cells
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: 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.
Best Overall Response (BOR)
The best efficacy recorded from the beginning of treatment to the progression or recurrence of the disease.
Time frame: 6 months
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: 6 months
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: 6 months
Overall survival (OS)
The period from the first infusion to any cause of death.
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Time frame: 6 months
Pharmacokinetics (PK) (Cmax)
The Peak Plasma concentration (Cmax) of amplified CNK-UT DNA in peripheral blood after infusion.
Time frame: up to 48 weeks
Pharmacokinetics (PK) (Tmax)
The time to reach the maximum concentration (Tmax)
Time frame: up to 48 weeks
Pharmacokinetics (PK)
The Area under the plasma concentration versus time curve (AUC) of amplified CNK-UT DNA in peripheral blood after infusion.
Time frame: up to 48 weeks
Levels of peripheral blood lymphocyte subsets
Percentage of CD45+CD3+TCR+T cell、CD3+CD8+ CD25+ CD69+T cell、CD3+CD4+CD25+ CD69+ T cell and Treg(CD4+CD25+FoxP3+)cell in peripheral blood detected by FCM after infusion.
Time frame: up to 48 weeks