Using engineered T-cells to treat severe Graft vs Host Disease

A Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of CNK-UT Cells to Treat the Patients With Steroid-refractory/Resistant or Steroid-dependent GVHD

This study is testing a new type of T-cell treatment for people with severe Graft vs Host Disease who haven't responded well to steroids, to see if it can help them feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 17 (estimated)
• Ages: 1 Year to 70 Years
• Sex: All
• Sponsor: Fujian Medical University (Academic / other)
• Drugs / interventions: ruxolitinib
• Locations: 1 site (Fuzhou, Fujian)
• Trial ID: NCT06568328 on ClinicalTrials.gov

What this trial studies

This pilot study evaluates the safety and effectiveness of chimeric natural killer receptor universal T-cells (CNK-UT) in patients suffering from steroid-refractory or steroid-dependent Graft vs Host Disease (GVHD) following allogeneic hematopoietic stem cell transplantation. It is a single-arm, open-label, phase I trial that will assess the pharmacokinetics and pharmacodynamics of the treatment. Participants will receive CNK-UT therapy and will be monitored for safety and tolerability, as well as treatment outcomes. The study aims to provide insights into a novel therapeutic approach for a challenging condition.

Who should consider this trial

Good fit: Ideal candidates are individuals aged 1 to 70 with grade II-IV steroid-refractory or steroid-dependent GVHD who have not responded to other treatments.

Not a fit: Patients with grade I GVHD or those who have not undergone allogeneic hematopoietic stem cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new option for patients with difficult-to-treat Graft vs Host Disease.

How similar studies have performed: While there have been studies on T-cell therapies for GVHD, the specific use of CNK-UT cells represents a novel approach that has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Aged 1\~70 years, male or female;
2. Participants diagnosed with grade II\~IV steroid-refractory/resistant or steroid-dependent GVHD after allogeneic hematopoietic stem cell transplantation who have failed treatment with ruxolitinib or at least one other second-line medication, or who are intolerant to these medications.
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.

Exclusion Criteria:

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.

Where this trial is running

Fuzhou, Fujian

• First Affiliated Hospital of Fujian Medical University — Fuzhou, Fujian, China (Recruiting)

Study contacts

• Principal investigator: Ting YANG, Prof. — First Affiliated Hospital of Fujian Medical University
• Study coordinator: Ting YANG, Prof.

Conditions Graft vs Host Disease; Chimeric natural killer receptor universal T-cells; steroid-refractory/resistant or steroid-dependent GVHD