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Clinical Trial NCT06750133 (CNK-UT) for Acute Graft-versus-Host Disease is recruiting. See the Trial Radar Card View and AI discovery tools for all the details. Or ask anything here.
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Universal CNK-UT Therapy for Refractory aGVHD Phase 1 23 Multi-Center Open-Label Investigator-Initiated

Recruiting
Clinical Trial NCT06750133 (CNK-UT) is designed to study Treatment for Acute Graft-versus-Host Disease. It is a Phase 1 interventional study that is recruiting, having started on 14 December 2024, with plans to enroll 23 participants. Led by First Affiliated Hospital of Zhejiang University, it is expected to complete by 30 June 2026. The latest data from ClinicalTrials.gov was last updated on 27 December 2024.
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.
Detailed Description
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...Show More
Official Title

A Study of Universal CNK-UT Cell Injection in Patients With Refractory Acute Graft-versus-host Disease

Conditions
Acute Graft-versus-Host Disease
Other Study IDs
  • CNK-UT
  • CNK-UT-IIT202305
NCT ID Number
NCT06750133
Start Date (Actual)
2024-12-14
Last Update Posted
2024-12-27
Completion Date (Estimated)
2026-06-30
Enrollment (Estimated)
23
Study Type
Interventional
PHASE
Phase 1
Status
Recruiting
Keywords
CNK-UT cell
aGVHD
allo-HSCT
steroids refractory
cellular therapy
Primary Purpose
Treatment
Design Allocation
N/A
Interventional Model
Sequential
Masking
None (Open Label)
Arms / Interventions
Participant Group/ArmIntervention/Treatment
ExperimentalCNK-UT cell Therapy
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.
Chimeric Natural Killer Receptor Universal T-cells (CNK-UT)
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, t...Show More
Primary Outcome Measures
Outcome MeasureMeasure DescriptionTime Frame
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 Outcome Measures
Outcome MeasureMeasure DescriptionTime Frame
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.
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.
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.
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.
6 months
Overall survival (OS)
The period from the first infusion to any cause of death.
6 months
Pharmacokinetics (PK) (Cmax)
The Peak Plasma concentration (Cmax) of amplified CNK-UT DNA in peripheral blood after infusion.
up to 48 weeks
Pharmacokinetics (PK) (Tmax)
The time to reach the maximum concentration (Tmax)
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.
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.
up to 48 weeks
Participation Assistant
Eligibility Criteria

Eligible Ages
Child, Adult, Older Adult
Minimum Age
14 Years
Eligible Sexes
All
  1. Aged 14-70 years, male or female;
  2. Participants diagnosed with grade II~IV steroid-refractory/resistant or steroid-dependent aGVHD after allogeneic hematopoietic stem cell transplantation.
  3. ECOG physical status score 0~3;
  4. Estimated life expectancy > 12 weeks;
  5. 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.
  6. Participants voluntarily participate in clinical trial; Understand and know this study, sign an informed consent form, and be willing to follow all experimental procedures.

  1. 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.
  2. Participants with a history of organ transplantation;
  3. Participants who have previously undergone more than one allogeneic hematopoietic stem cell transplantation.
  4. 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)..
  5. 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).
  6. 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.
  7. Severe infections that are active or poorly controlled clinically.
  8. Participants who have received treatment from other clinical trials within 12 weeks prior to the initiation of the study.
  9. Participants who have previously used any gene therapy products prior to the initiation of the study.
  10. Allergic to components of CNK-UT injection.
  11. Participants suffer from known mental or substance abuse disorders, which may interfere with their ability to comply with research requirements.
  12. Women who are pregnant or breastfeeding, as well as male or female participants who have planned for birth within 1 year after receiving medication.
  13. 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.
  14. Other situations that the participant is identified by the investigator as unsuitable to participate in the study.
First Affiliated Hospital of Zhejiang University logoFirst Affiliated Hospital of Zhejiang University
ST Phi Therapeutics Co., Ltd logoST Phi Therapeutics Co., Ltd
Study Responsible Party
Yi Luo, Principal Investigator, Professor, First Affiliated Hospital of Zhejiang University
Study Central Contact
Contact: Li Luo, MD, +860571-87233801, [email protected]
Contact: Yibo Wu, MD, +860571-87233801, [email protected]
2 Study Locations in 1 Countries

Fujian

First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
Ting Yang, MD, Contact, 86-591-88711593, [email protected]
Recruiting

Zhejiang

The first affiliated hospital of zhejiang university, school of medicine., Hangzhou, Zhejiang, 310000, China
Duo Lv, MD, Contact, +860571-87236560, [email protected]
Recruiting