Neuroblastoma, Recurrent, RefractoryPhase 1NCT06751134
Chimeric Natural Killer Receptor-Universal T Cells for Relapsed or Refractory Neuroblastoma
A Phase 1 study testing Chimeric Natural Killer Receptor Universal T-cells (CNK-UT) in people with Neuroblastoma, Recurrent, Refractory, run by Nanjing Children's Hospital at 2 sites in China.
Trial summary
This is a single arm, open-label, multi-center, pilot studies (Investigator Initiated Trial, IIT) to evaluate the safety, preliminary efficacy, pharmacokinetics of universal T-cells engineered with chimeric natural killer receptor (CNK-UT) to treat the patients with relapsed/refractory Neuroblastoma. Read more about this study
- Who is it for?
- Ages 1 year to 12 years
- Conditions the study is for
- Neuroblastoma, Recurrent, Refractory
- 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
- 12 participants
- Where
- 2 sitesChina
- Study dates
- 28 Dec 2024to 1 Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Aged 1-12 years with weight≥10kg, male or female;
- The child and/or guardian has signed the informed consent form (ICF) and has the ability to comply with the study requirements.
- Diagnosed with relapsed/refractory neuroblastoma. Clinical diagnostic criteria and first-line standard treatment can refer to the NCCN guidelines:
- Relapsed neuroblastoma: New lesions appear at the primary site or other locations 4 weeks after achieving complete remission through first-line standard treatment.
- Refractory neuroblastoma: Failure to achieve complete remission after standard treatment protocols, which include induction chemotherapy, surgery, and radiotherapy targeting the primary tumor and residual metastatic sites;
- Prior to enrollment, appropriate measures can be implemented to ensure that the subject's disease status is either partial remission (PR) or stable disease (SD).
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- According to the INRC efficacy criteria, there must be at least one lesion whose efficacy can be assessed through functional imaging (123I-MIBG) and/or bone marrow examination (bone marrow aspiration or biopsy). If soft tissue lesions are present, the longest diameter of the target lesion should be ≤2 cm.
- Tumor tissue sections or paraffin blocks can be provided, and it has been confirmed through immunohistochemistry (IHC) that the tumor tissue expresses B7-H3.
- Lansky score>60；
- Estimated life expectancy > 12 weeks;
- Adequate organ and bone marrow function, and the laboratory test value meets the following requirements within 7 days before enrollment, as follows:
- (1)Blood Routine Test: Absolute neutrophil count(ANC)≥1.5×10^9/L;Absolute lymphocyte count (ALC)≥0.2×10^9/L；Platelet count ≥75×10^9/L; Haemoglobin≥90g/L; (2)Heart: Left ventricular ejection fraction (LVEF)≥50%;Cardiac function Grade I-II; (3)Pulmonary function: indoor oxygen saturation≥92%. (4)Hepatic function：Total bilirubin≤3×ULN; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)≤5×ULN; (5)Renal function: Serum creatinine≤2×ULN, or Creatinine clearance rate (CCR)≥60 mL/min (Cockroft-Gault formula); 10.All toxic responses originating from previous radiotherapy, chemotherapy, or other treatments (occurring within 4 weeks or 5 half-lives of anti-tumor drugs therapy [including but not limited to chemotherapy, targeted therapy, immunotherapy, Chinese herbal medicine]) have returned to NCI CTCAEV5.0 Grade≤1 (except for hair loss).
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 symptomatic central nervous system (CNS) metastasis confirmed by imaging or pathological examination.
- Participants with MIBG non-avid disease.
- Participants with a history of organ transplantation（excluding stem cell transplantation）;
- Participants with active autoimmune diseases requiring systemic treatment (such as the use of disease-modifying drugs, corticosteroids, or immunosuppressants) are considered. The use of replacement therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) is permitted. A known history of primary immunodeficiency is also noted. For patients who only test positive for autoimmune antibodies, the presence of autoimmune disease must be confirmed based on the investigator's judgment.
- Uncontrolled or irreparable systemic diseases, metabolic disorders, or other non-malignant organ diseases or cancer sequelae, which may lead to higher medical risks and/or uncertainties in survival assessment.
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- 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 either active or poorly controlled clinically within 4 weeks prior to enrollment, including but not limited to hospitalization due to infections, bacteremia, or severe pneumonia complications (excluding mild urinary tract infections and upper respiratory tract infections).
- Received radiotherapy, chemotherapy (excluding lymphodepletion), molecular targeted therapy, immune checkpoint inhibitors, or other anti-tumor treatments within 4 weeks or 5 half-lives (whichever is shorter) before cell infusion..
- Participants who have undergone major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the initiation of the study, or have severe unhealed wounds, ulcers, or fractures.
- Participants who have received treatment from other clinical trials within 4 weeks prior to the initiation of the study.
- Participants who receive attenuated live vaccines within 4 weeks prior to the initiation of the study.
- Participants who have used any gene therapy products prior to cell infusion.
- 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.
- Participants considered by the investigator to have other potentially life-threatening serious complications that may interfere with the evaluation of this study..
- Other situations that the participant is identified by the investigator as unsuitable to participate in the study.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Nanjing Children's Hospital
Nanjing, Jiangsu, 210000
Yongjun Fang, MD, +86025-52862937, fyj322@189.cn
- Recruiting
Nanjing
Nanjing, Jiangsu
About this study
Official title: A Study to Evaluate the Safety, Preliminary Efficacy, Pharmacokinetics of CNK-UT Cells to Treat the Patients with Relapsed/refractory Neuroblastoma
This is a single arm, open-label, multi-center, pilot studies (Investigator Initiated Trial, IIT) to evaluate the safety, preliminary efficacy, pharmacokinetics of universal T-cells engineered with chimeric natural killer receptor (CNK-UT) to treat the patients with relapsed/refractory Neuroblastoma.
Read the detailed description
This is a single arm, open-label, phase I, dose escalation/dose expansion study to assess the safety of CNK-UT cells therapy, and to obtain the preliminary efficacy and pharmacokinetics result in participants who have been diagnosed with relapsed/refractory Neuroblastoma.
- Conditions
- Neuroblastoma, Recurrent, Refractory
- Being tested
- Chimeric Natural Killer Receptor Universal T-cells (CNK-UT)
- Keywords
- Chimeric natural killer receptor universal T-cells, relapsed/refractory Neuroblastoma
- Medical subject headings
- Neuroblastoma, Recurrence
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)Drug
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 (3~34×10^7 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 (3~34×10^7 CNK+ cells/kg).
2. Dose Expansion:
Multiple-dose intravenous injection of CNK-UT cells according to the results of dose escalation. Receives: Drug: 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
Secondary outcomes (7)
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: up to 1 year
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: up to 1 year
Disease control rate (DCR)
The number of cases in which response are achieved from the start of cells infusion/the total number of evaluable cases (%).
Measured: up to 1 year
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: up to 1 year
Overall survival (OS)
The period from the first infusion to any cause of death.
Measured: up to 1 year
Pharmacokinetics (PK) (Cmax)
The Peak Plasma concentration (Cmax) of amplified CNK-UT DNA in peripheral blood after infusion.
Measured: up to 1 year
Pharmacokinetics (PK) (Tmax)
The time to reach the maximum concentration (Tmax).
Measured: up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2024
- Study start28 Dec 2024
- Primary completion1 Jul 2026 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuroblastoma, Recurrent, RefractoryStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nanjing Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Fang Yongjun, Nanjing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06751134
- Sponsor's protocol ID
- CNK-UT-IIT202304
- Status last verified
- Feb 2025
- First submitted
- 20 Dec 2024
- Last updated
- 7 Feb 2025
- 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 7 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Evaluate the Safety, Preliminary Efficacy, Pharmacokinetics of CNK-UT Cells to Treat the Patients with Relapsed/refractory Neuroblastoma
- ClinicalTrials.gov ID
- NCT06751134
- Acronym / sponsor ID
- CNK-UT-IIT202304
- Conditions
- Neuroblastoma, Recurrent, Refractory
- Keywords
- Chimeric natural killer receptor universal T-cells, relapsed/refractory Neuroblastoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Nanjing Children's HospitalUniversity, hospital or other
- Study start
- 28 Dec 2024 (actual)
- Primary completion
- 1 Jul 2026 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 27 Dec 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, preliminary efficacy, pharmacokinetics of universal T-cells engineered with chimeric natural killer receptor (CNK-UT) to treat the patients with relapsed/refractory Neuroblastoma.
Detailed description
This is a single arm, open-label, phase I, dose escalation/dose expansion study to assess the safety of CNK-UT cells therapy, and to obtain the preliminary efficacy and pharmacokinetics result in participants who have been diagnosed with relapsed/refractory Neuroblastoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CNK-UT cells therapy | Experimental | Drug: Chimeric Natural Killer Receptor Universal T-cells (CNK-UT)1. Dose Escalation： Single-dose intravenous injection of CNK-UT cells (3~34×10^7 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 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (12 listed)
- Aged 1-12 years with weight≥10kg, male or female;
- The child and/or guardian has signed the informed consent form (ICF) and has the ability to comply with the study requirements.
- Diagnosed with relapsed/refractory neuroblastoma. Clinical diagnostic criteria and first-line standard treatment can refer to the NCCN guidelines:
- Prior to enrollment, appropriate measures can be implemented to ensure that the subject's disease status is either partial remission (PR) or stable disease (SD).
- According to the INRC efficacy criteria, there must be at least one lesion whose efficacy can be assessed through functional imaging (123I-MIBG) and/or bone marrow examination (bone marrow aspiration or biopsy). If soft tissue lesions are present, the longest diameter of the target lesion should be ≤2 cm.
Key exclusion criteria (17 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 symptomatic central nervous system (CNS) metastasis confirmed by imaging or pathological examination.
- Participants with MIBG non-avid disease.
- Participants with a history of organ transplantation（excluding stem cell transplantation）;
- Participants with active autoimmune diseases requiring systemic treatment (such as the use of disease-modifying drugs, corticosteroids, or immunosuppressants) are considered. The use of replacement therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) is permitted. A known history of primary immunodeficiency is also noted. For patients who only test positive for autoimmune antibodies, the presence of autoimmune disease must be confirmed based on the investigator's judgment.
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 (3~34×10^7 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. | Drug | 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
7 secondary outcomes
Objective Response Rate (ORR)
Time frame: up to 1 year
Duration of Response (DOR)
Time frame: up to 1 year
Disease control rate (DCR)
Time frame: up to 1 year
Progression-free Survival (PFS)
Time frame: up to 1 year
Overall survival (OS)
Time frame: up to 1 year
Pharmacokinetics (PK) (Cmax)
Time frame: up to 1 year
Pharmacokinetics (PK) (Tmax)
Time frame: up to 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2025.
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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.
2 sites 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 Neuroblastoma, Recurrent, Refractory, run by Nanjing Children's Hospital at 2 sites 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 12 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 7 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Fang Yongjun, Prof. (025-52862937, fyj322@189.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). 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 7 Feb 2025.