Chimeric Natural Killer Receptor-Universal T Cells for Refractory GVHD

NCT06568328 | Recruiting Phase 1

• 1 other identifier: CNK-UT-IIT202303
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Graft vs Host Disease

Keywords

Chimeric natural killer receptor universal T-cells; steroid-refractory/resistant or steroid-dependent GVHD

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)

  6 months

• 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 (2)

• Biomarkers

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

• HLA typing

  Enrollment.

Study Arms (1)

CNK-UT cells therapy

EXPERIMENTAL

1. Dose Escalation：Single-dose intravenous injection of CNK-UT cells (1\~10×10\^7 CNK+ cells/kg). 2. Dose Expansion：Multiple-dose intravenous injection of CNK-UT cells 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

OUTLINE: This is a dose-escalation study of CNK-UT cells followed by a dose-expansion study. 1. Dose Escalation (Single Ascending Dose Study, SAD): During SAD study stage, the participants will be intravenous infused with CNK-UT cells (1\~10×10\^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. 2. Dose Expansion (multiple ascending dose study, MAD): During MAD study stage, the participants will receive multiple doses of CNK-UT cells. The dosage and frequency of drug administration in the dose expansion stage can be adjusted and determined according to the SAD study.

CNK-UT cells therapy

Eligibility Criteria

• Age: 1 Year - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 1\~70 years, male or female;
• 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.
• 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

• Fujian Medical University: lead

Study Sites (1)

First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, China

RECRUITING

MeSH Terms

Conditions

Graft vs Host Disease

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Ting YANG, Prof.

  First Affiliated Hospital of Fujian Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ting YANG, Prof.

CONTACT

86-591-88711593; yang.hopeting@gmail.com

Jianda HU, Prof.

CONTACT

86-591-88711593; drjiandahu@163.com

Study Design

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

Study Record Dates

• First Submitted: August 3, 2024
• First Posted: August 23, 2024
• Study Start: September 1, 2024
• Primary Completion: January 1, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: August 23, 2024

Record last verified: 2024-08

Locations

CN (1)