Universal CNK-UT Therapy for Refractory aGVHD

NCT06750133 | Recruiting Phase 1 DMC

• 1 other identifier: CNK-UT-IIT202305
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Acute Graft-versus-Host Disease

Keywords

CNK-UT cell; aGVHD; allo-HSCT; steroids refractory; cellular therapy

Outcome Measures

Primary Outcomes (2)

• 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

  up to 1 year

• Identification of Maximum Tolerated Dose (MTD) & incidence of Dose-limiting Toxicities (DLTs)

  Incidence of dose-limiting toxicities (DLTs)

  up to 21 days since first infusion of CNK-UT cells

Secondary Outcomes (9)

• 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.

• Best Overall Response (BOR)

  6 months

• Duration of Response (DOR)

  6 months

• Progression-free Survival (PFS)

  6 months

• Overall survival (OS)

  6 months

Other Outcomes (5)

• Biomarkers

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

• HLA typing

  Enrollment.

• Incidence of virus infection

  up to 48 weeks

Study Arms (1)

CNK-UT cell Therapy

EXPERIMENTAL

1. Dose Escalation：Single-dose intravenous injection of CNK-UT cells (3×10\^7 CNK+ cells/kg). 2. Dose Expansion：Multiple-dose intravenous injection of CNK-UT cells (6-10×10\^7 CNK+ cells/kg)according to the results of dose escalation.

Biological: Chimeric Natural Killer Receptor Universal T-cells (CNK-UT)

Interventions

Chimeric Natural Killer Receptor Universal T-cells (CNK-UT) BIOLOGICAL

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.

CNK-UT cell Therapy

Eligibility Criteria

• Age: 14 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Female participants of childbearing age must undergo a serum or urine pregnancy test before enrollment, and the results must be negative, and agree to take acceptable measures to minimize the possibility of pregnancy during the trial; For female participants of childbearing age or male participants whose sexual partners are women of childbearing age, effective contraceptive measures should be taken during the study and for at least 6 months following the last dose of the study cells infusion.
• Participants voluntarily participate in clinical trial; Understand and know this study, sign an informed consent form, and be willing to follow all experimental procedures.

You may not qualify if:

• 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)..
• Systemic diseases deemed unstable by principal investigator include, but are not limited to, severe pulmonary, hepatic, renal, or metabolic disorders that require pharmacological intervention (excluding complications related to allogeneic hematopoietic stem cell transplantation).
• Active pulmonary tuberculosis (TB), who is receiving anti-tuberculosis treatment or has received anti-tuberculosis treatment within 1 year before enrollment; human immunodeficiency virus (HIV) infection, known syphilis infection.
• Severe infections that are active or poorly controlled clinically.
• Participants who have received treatment from other clinical trials within 12 weeks prior to the initiation of the study.
• Participants who have previously used any gene therapy products prior to the initiation of the study.
• Allergic to components of CNK-UT injection.
• Participants suffer from known mental or substance abuse disorders, which may interfere with their ability to comply with research requirements.
• Women who are pregnant or breastfeeding, as well as male or female participants who have planned for birth within 1 year after receiving medication.
• Uncontrolled/uncorrectable metabolic disorders or other non-malignant organ diseases or systemic diseases or secondary reactions to cancer, which can lead to higher medical risk and/or uncertainty in survival assessments.
• Other situations that the participant is identified by the investigator as unsuitable to participate in the study.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead
• ST Phi Therapeutics Co., Ltd: collaborator

Study Sites (2)

First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, China

RECRUITING

The first affiliated hospital of zhejiang university, school of medicine.

Hangzhou, Zhejiang, 310000, China

RECRUITING

Study Officials

• He Huang, PHD

  First Affiliated Hospital of Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Li Luo, MD

CONTACT

+860571-87233801; luoyijr@zju.edu.cn

Yibo Wu, MD

CONTACT

+860571-87233801; wuyibo7@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 20, 2024
• First Posted: December 27, 2024
• Study Start: December 14, 2024
• Primary Completion: December 14, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: after the clinical trial completed
• Access Criteria: contact with Principal Investigator

Locations

CN (2)