Universal CNK-UT Therapy for Refractory aGVHD

ConditionAcute Graft-versus-Host Disease

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age14-70

SponsorFirst Affiliated Hospital of Zhejiang University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Aged 14-70 years, male or female;

Participants diagnosed with grade II~IV steroid-refractory/resistant or steroid-dependent aGVHD after allogeneic hematopoietic stem cell transplantation.

ECOG physical status score 0~3;

Estimated life expectancy > 12 weeks;

Disqualifiers

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 a history of organ transplantation;

Participants who have previously undergone more than one allogeneic hematopoietic stem cell transplantation.

Uncontrolled hypertension as determined by principal investigator, a history of hypertensive crisis or hypertensive encephalopathy; symptomatic congestive heart failure (New York Heart Association classification III-IV); symptomatic or poorly controlled arrhythmias; a history of congenital long QT syndrome or a corrected QT interval (QTc) > 500 ms at screening (calculated using the Fridericia method)..

Trial design

Design model

Sequential

Treatments tested in this trial

Chimeric Natural Killer Receptor Universal T-cells (CNK-UT)
Biological/Vaccine
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.

Treatment groups

23 Participants

are divided into 1 treatment group

Group A: CNK-UT cell TherapyExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

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

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

Secondary outcomes

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

Other outcomes

Biomarkers

ST2、REG3α and Elafin will be analyzed

Time frame

Enrollment and evaluated as complete remission (CR), or if necessary，up to 48 weeks

HLA typing

Evaluate the impact of HLA typing matching between donors and participants on the survival time and efficacy of CNK-UT in vivo.

Time frame

Enrollment.

Incidence of virus infection

In this study, all subjects were tested for aGVHD-associated virus infection, including cytomegalovirus and Epstein-Barr virus.

Time frame

up to 48 weeks

long-term survival

long-term survival of patients accepted universal CNK-UT cell injection therapy

Time frame

5 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

First Affiliated Hospital of Zhejiang University

Lead sponsor

ST Phi Therapeutics Co., Ltd

Collaborator

Source ClinicalTrials.gov

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