Clinical trial NCT06568328: Chimeric Natural Killer Receptor-Universal T Cells for Refractory GVHD
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Graft vs Host Disease
Keywords: Chimeric natural killer receptor universal T-cells
steroid-refractory/resistant or steroid-dependent GVHD
Lead sponsor: Fujian Medical University
Sponsor class: OTHER
First posted: 2024-08-23
Enrollment: 17
Sex: ALL
Minimum age (years): 1
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 GVHD.

Detailed description: This is a single arm, open-label, phase I, dose escalation/dose expansion study to assess the safety and tolerability of CNK-UT cells therapy, and to obtain the efficacy, pharmacokinetics and pharmacodynamics result in participants who have been diagnosed with steroid-refractory/resistant or steroid-dependent GVHD.

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.

Primary outcomes:
measure: Incidence of Treatment Related adverse events (AEs)
timeFrame: up to 1 year
measure: Identification of Maximum Tolerated Dose (MTD) & incidence of Dose-limiting Toxicities (DLTs)
timeFrame: up to 21 days since first infusion of CNK-UT cells
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 6 months
measure: Best Overall Response (BOR)
timeFrame: 6 months
measure: Duration of Response (DOR)
timeFrame: 6 months
measure: Progression-free Survival (PFS)
timeFrame: 6 months
measure: Overall survival (OS)
timeFrame: 6 months
measure: Pharmacokinetics (PK) (Cmax)
timeFrame: up to 48 weeks
measure: Pharmacokinetics (PK) (Tmax)
timeFrame: up to 48 weeks
measure: Pharmacokinetics (PK)
timeFrame: up to 48 weeks
measure: Levels of peripheral blood lymphocyte subsets
timeFrame: up to 48 weeks
Other outcomes:
measure: Biomarkers
timeFrame: Enrollment and evaluated as complete remission (CR), or if necessary，up to 48 weeks
measure: HLA typing
timeFrame: Enrollment.
Locations:
city: Fuzhou
country: China
facility: First Affiliated Hospital of Fujian Medical University
state: Fujian
Study officials:
affiliation: First Affiliated Hospital of Fujian Medical University
name: Ting YANG, Prof.
role: PRINCIPAL_INVESTIGATOR
References: