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

Overview

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.

Interventions

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

Primary outcome measures

• Incidence of Treatment Related adverse events (AEs) [Time frame: up to 1 year]
• Identification of Maximum Tolerated Dose (MTD) & incidence of Dose-limiting Toxicities (DLTs) [Time frame: up to 21 days since first infusion of CNK-UT cells]

Secondary outcome measures (9)

• Objective Response Rate (ORR) [Time frame: 6 months]
• Best Overall Response (BOR) [Time frame: 6 months]
• Duration of Response (DOR) [Time frame: 6 months]
• Progression-free Survival (PFS) [Time frame: 6 months]
• Overall survival (OS) [Time frame: 6 months]
• Pharmacokinetics (PK) (Cmax) [Time frame: up to 48 weeks]
• Pharmacokinetics (PK) (Tmax) [Time frame: up to 48 weeks]
• Pharmacokinetics (PK) [Time frame: up to 48 weeks]
• Levels of peripheral blood lymphocyte subsets [Time frame: up to 48 weeks]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• First Affiliated Hospital of Fujian Medical University — Fuzhou

Identifiers

NCT: NCT06568328 · CNK-UT-IIT202303

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗