Graft vs Host DiseasePhase 1NCT06568328
Chimeric Natural Killer Receptor-Universal T Cells for Refractory GVHD
A Phase 1 study testing Chimeric Natural Killer Receptor Universal T-cells (CNK-UT) in people with Graft vs Host Disease, run by Fujian Medical University at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 1 year to 70 years
- Conditions the study is for
- Graft vs Host Disease
- What is being tested?
- Chimeric Natural Killer Receptor Universal T-cells (CNK-UT)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2024to 31 Aug 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian
Ting YANG, Prof., 86-591-88711593, yang.hopeting@gmail.com
Ting YANG, Prof.
About this study
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
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.
Read the 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.
- Conditions
- Graft vs Host Disease
- Being tested
- Chimeric Natural Killer Receptor Universal T-cells (CNK-UT)
- Keywords
- Chimeric natural killer receptor universal T-cells, steroid-refractory/resistant or steroid-dependent GVHD
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
- 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.
- 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: Chimeric Natural Killer Receptor Universal T-cells (CNK-UT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: up to 1 year
Identification of Maximum Tolerated Dose (MTD) & incidence of Dose-limiting Toxicities (DLTs)
Incidence of dose-limiting toxicities (DLTs)
Measured: up to 21 days since first infusion of CNK-UT cells
Secondary outcomes (9)
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.
Measured: 6 months
Best Overall Response (BOR)
The best efficacy recorded from the beginning of treatment to the progression or recurrence of the disease.
Measured: 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.
Measured: 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.
Measured: 6 months
Overall survival (OS)
The period from the first infusion to any cause of death.
Measured: 6 months
Pharmacokinetics (PK) (Cmax)
The Peak Plasma concentration (Cmax) of amplified CNK-UT DNA in peripheral blood after infusion.
Measured: up to 48 weeks
Pharmacokinetics (PK) (Tmax)
The time to reach the maximum concentration (Tmax)
Measured: 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.
Measured: 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.
Measured: up to 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2024
- Study start1 Sep 2024 (estimated)
- Primary completion1 Jan 2026 (estimated)
- Study completion31 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft vs Host DiseaseStudies of the same condition, open and under way.
- More trials run by Fujian Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fujian Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ting YANG, Fujian Medical University
- Investigators
- Ting YANG, Prof., Principal investigator, First Affiliated Hospital of Fujian Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06568328
- Sponsor's protocol ID
- CNK-UT-IIT202303
- Status last verified
- Aug 2024
- First submitted
- 3 Aug 2024
- Last updated
- 23 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06568328
- Acronym / sponsor ID
- CNK-UT-IIT202303
- Conditions
- Graft vs Host Disease
- Keywords
- Chimeric natural killer receptor universal T-cells, steroid-refractory/resistant or steroid-dependent GVHD
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 17 participants (estimated)
- Lead sponsor
- Fujian Medical UniversityUniversity, hospital or other
- Study start
- 1 Sep 2024 (estimated)
- Primary completion
- 1 Jan 2026 (estimated)
- Study completion
- 31 Aug 2026 (estimated)
- First posted
- 23 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CNK-UT cells therapy | Experimental | Biological: Chimeric Natural Killer Receptor Universal T-cells (CNK-UT)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. |
Who may qualify
- Ages
- 1 year to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (14 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 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. | Biological | CNK-UT cells therapy |
Primary outcome
Incidence of Treatment Related adverse events (AEs)
Time frame: up to 1 year
Incidence of Treatment Related AEs, AEs of special interest and serious adverse events (SAEs) assessed by NCI-CTCAE v5.0 criteria
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
Incidence of dose-limiting toxicities (DLTs)
9 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ting YANG, Prof. principal investigator
First Affiliated Hospital of Fujian Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Chimeric Natural Killer Receptor Universal T-cells (CNK-UT) in people with Graft vs Host Disease, run by Fujian Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ting YANG, Prof. (86-591-88711593, yang.hopeting@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment Related adverse events (AEs) (time frame: up to 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2024.