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

Официальное название

A Study to Evaluate the Safety, Preliminary Efficacy, Pharmacokinetics of CNK-UT Cells to Treat the Patients with Relapsed/refractory Neuroblastoma

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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

Первичные конечные точки

• Incidence of Treatment Related adverse events (AEs) [Срок оценки: up to 1 year]

Вторичные конечные точки (7)

• Objective Response Rate (ORR) [Срок оценки: up to 1 year]
• Duration of Response (DOR) [Срок оценки: up to 1 year]
• Disease control rate (DCR) [Срок оценки: up to 1 year]
• Progression-free Survival (PFS) [Срок оценки: up to 1 year]
• Overall survival (OS) [Срок оценки: up to 1 year]
• Pharmacokinetics (PK) (Cmax) [Срок оценки: up to 1 year]
• Pharmacokinetics (PK) (Tmax) [Срок оценки: up to 1 year]

Критерии участия

Критерии включения

• 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).

Критерии исключения

• 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.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Nanjing Children's Hospital — Нанкин
• Nanjing — Нанкин

Идентификаторы

NCT: NCT06751134 · CNK-UT-IIT202304

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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