Adoptive TKC Transfer Combined With Chemotherapy for Advanced Non-small Cell Lung Cancer (NSCLC)
A Clinical Study on the Safety and Efficacy of Adoptive TKC Transfer Combined With Chemotherapy for Advanced Non-small Cell Lung Cancer (NSCLC)
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Descripción detallada
Primary Objective:
● To describe the safety profile and toxicity tolerance of combining adoptive TKC transfer with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).
Secondary Objectives:
● To evaluate the preliminary efficacy of combining adoptive TKC transfer with chemotherapy in the treatment of advanced NSCLC.
Design:
- This is a single-centre, open label, non-randomised, no control clinical trial.
- NK cells and γδT cells are isolated from the patients' peripheral blood mononuclear cells (PBMCs) obtained before chemotherapy and then co-cultured with TKC technology ex-vivo. The mixed cultures will be used in multiple infusions under administration. The first infusion will be conducted in 7-10 days after chemotherapy and is assessed by the investigators.
- Clinical responses will be evaluated closely in about 30 days and last up to 2 years after treatment.
Tipo de estudio
Tipo de estudio
Inscripción (Anticipado)
Inscripción
Fase
Fase
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
Estudio Contacto
- Nombre: Haichuan Su
- Número de teléfono: 18629190366
- Correo electrónico: suhc@fmmu.edu.cn
Ubicaciones de estudio
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Shanxi
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Xi'an, Shanxi, Porcelana, 710038
- Reclutamiento
- Tangdu Hospital, Fourth Military Medical University
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Contacto:
- Haichuan Su
- Número de teléfono: 18629190366
- Correo electrónico: suhc@fmmu.edu.cn
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-
Criterios de participación
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Aged≥18 years old and ≤70 years old when signing the informed consent; regardless of gender;
- Body weight>40kg;
- Histopathology or cytology confirmed as advanced NSCLC which is not suitable for radical surgical resection;
- At least one measurable lesion according to the RECIST 1.1 criteria; according to the CT or MRI cross-sectional imaging, the diameter of a single lesion ≤8 cm, or the maximum diameter of a single lesion ≤5 cm and the number of lesions ≤5 (including metastatic lesions).
- Imaging examination showed no tumor thrombus in the portal vein/inferior vena cava;
- Acceptable hemopoietic ability: hemoglobin (HGB) >90g/L (no blood transfusion within two weeks), absolute neutrophil count (ANC) >1.5×10^9/L, platelet count >1.0×10^11/L, absolute lymphocyte count (ALC)>500×10^9/L;
- Prothrombin time (PT)/international normalized ratio (INR) <1.5 ULN and partial thromboplastin time (PTT)/activated partial thromboplastin time (APTT) <1.5 ULN;
- Acceptable liver and kidney functions: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 ULN in subjects without liver metastases and ≤3.5 upper limit of normal (ULN) in those with liver metastases; bilirubin≤1.5 ULN (excluding hyperbilirubinemia or non-liver-derived hyperbilirubinemia); creatinine ≤1.5 ULN and creatinine clearance rate≥40 mL/min;
- Women of child-bearing age must be negative for pregnancy test at 7 days before initiation of the treatment.
- Eastern Cooperative Oncology Group (ECOG) scores≤1.
- Expected survival no less than 6 months.
Exclusion Criteria:
- History of any chemotherapy within 2 weeks before a single blood collection;
- Participating in other clinical trials in the past 30 days;
- Current on systemic steroid or steroid inhalers;
- Active brain metastasis or spinal cord compression
- Uncontrollable pleural and peritoneal effusion requiring clinical treatment or intervention;
- Active bleeding, and thrombotic diseases requiring treatment;
- Uncontrolled infectious diseases, such as baseline hepatitis B virus (HBV) DNA≥2000 IU/mL, positive for anti-human immunodeficiency virus (HIV) antibody and hepatitis C virus (HCV)-RNA; Other active infection with clinical significance;
- Organ failure; Heart: Grade III and IV ; or with hypertension uncontrolled by the standard treatment, history of myocarditis or myocardial infarction within 1 year; Liver: Class C according to the Child-Turcottei-Pugh System (CTP); Kidneys: Kidney failure and uremic syndrome; Lungs: Serious symptoms of respiratory failure; Brain: Disturbance of consciousness;
- Allergic diathesis and allergic to immunotherapy or relevant drugs;
- Pregnancy or lactation;
- History of other active malignancies in the past 5 years, excluding basal or squamous skin carcinoma, superficial bladder cancer, and breast cancer in situ which have completely healed and require no follow-up treatment;
- Serious autoimmune diseases or immunodeficiency disease, including those with confirmed severe autoimmune diseases and requiring long-term use (over 2 months) of systemic immunosuppressants (steroids) or having immune-mediated symptomatic diseases, such as ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE) and autoimmune vasculitis (eg., Wegener's granulomatosis);
- Any mental diseases, including dementia and changes in mental status that may influence the understanding about the informed consent and questionnaire;
- Judged as serious uncontrollable diseases by the researchers, or other conditions that may interfere with the treatment and therefore being ineligible.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Número de brazos
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
|---|---|
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Experimental: adoptive TKC transfer combined with chemotherapy
NK cells and γδT cells are isolated from the patients' PBMCs obtained before standard chemotherapy and then co-cultured ex-vivo.
Patients will receive multiple TKC treatments under administration, 3 weeks/cycle.
The first infusion will be conducted in 7-10 days after chemotherapy and is assessed by the investigators.
TKC cells are transfused to patients in a dosage escalated manner.
Dose escalation starts at 1×10^8 cells/kg (based on the whole body weight).
After the safety assurance of the initial administration, the next course, up to 8 courses, is resumed and the dose maybe increased subsequently at the discretion of the investigators, or reduced for safety reason.
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Standard chemotherapy drug
TKC: co-cultured autologous NK cells and γδT cells
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¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Safety evaluation by the incidence of adverse events (AEs) and serious adverse events (SAEs)
Periodo de tiempo: 24 months
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Incidence of AEs and SAEs of each participant will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
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24 months
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Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Overall response rate (ORR)
Periodo de tiempo: 24 months
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ORR is defined as the percentage of patients who have a clinical response (objective tumor regression).ORR is computed by: the sum of the number of patients with Complete Response (CR) and number of patients with Partial Response (PR) / total number of patients.
The total number of patients is the sum of the number of patients with CR, PR, stable disease (SD) or progressive disease (PD).
The Response Evaluation Criteria in Solid Tumors (RECIST v1.1) is used as the criteria to determine whether a tumor disappears (CR), shrinks (PR), stays the same (SD) or gets bigger (PD).
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24 months
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Duration of response (DOR)
Periodo de tiempo: 24 months
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DOR is the time between the initial response to treatment per RECIST v1.1 and subsequent disease progression among patients achieving Complete Response (CR) or Partial Response (PR).
RECIST v1.1 is used as the criteria to determine whether a tumor disappears (CR) or shrinks (PR).
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24 months
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Progression-free survival (PFS)
Periodo de tiempo: 24 months
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PFS is the length of time from the date patient enrolled in to the date on which tumor progresses or the patient dies for any cause.
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24 months
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Colaboradores e Investigadores
Patrocinador
Patrocinador
Colaboradores
Colaboradores
Investigadores
Investigadores
- Silla de estudio: Helong Zhang, IEC of Institution for National Drug Clinical Trials ,Tangdu Hospital
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Anticipado)
Inicio del estudio
Finalización primaria (Anticipado)
Finalización primaria
Finalización del estudio (Anticipado)
Finalización del estudio
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Publicado por primera vez
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
Otros números de identificación del estudio
- SHKYSW-TKC-CAN-102
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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