Chimeric Natural Killer Receptor-Universal T Cells for Relapsed or Refractory Neuroblastoma

NCT06751134 | Recruiting Phase 1

• 1 other identifier: CNK-UT-IIT202304
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Neuroblastoma, Recurrent, Refractory

Keywords

Chimeric natural killer receptor universal T-cells, relapsed/refractory Neuroblastoma

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (7)

• Objective Response Rate (ORR)

  up to 1 year

• Duration of Response (DOR)

  up to 1 year

• Disease control rate (DCR)

  up to 1 year

• Progression-free Survival (PFS)

  up to 1 year

• Overall survival (OS)

  up to 1 year

Other Outcomes (2)

• biomarkers

  up to 1 year

• Levels of peripheral blood lymphocyte subsets

  up to 1 year

Study Arms (1)

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.

Drug: Chimeric Natural Killer Receptor Universal T-cells (CNK-UT)

Interventions

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. 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.

CNK-UT cells therapy

Eligibility Criteria

• Age: 1 Year - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).
• 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).

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 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.
• 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.

Sponsors & Collaborators

• Nanjing Children's Hospital: lead

Study Sites (2)

Nanjing Children's Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

Nanjing

Nanjing, Jiangsu, China

RECRUITING

MeSH Terms

Conditions

Neuroblastoma; Recurrence

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Fang Yongjun, Prof.

CONTACT

025-52862937; fyj322@189.com

Study Design

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

Study Record Dates

• First Submitted: December 20, 2024
• First Posted: December 27, 2024
• Study Start: December 28, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 7, 2025

Record last verified: 2025-02

Locations

CN (2)