Esta página se tradujo automáticamente y no se garantiza la precisión de la traducción. por favor refiérase a versión inglesa para un texto fuente.

Adoptive TKC Transfer Combined With Chemotherapy for Advanced Non-small Cell Lung Cancer (NSCLC)

26 de julio de 2021 actualizado por: suhaichuan

A Clinical Study on the Safety and Efficacy of Adoptive TKC Transfer Combined With Chemotherapy for Advanced Non-small Cell Lung Cancer (NSCLC)

Innate immune cells are an important part of the body's innate immune system, the first line of defense against infection and cancer. Tumor killer cells (TKC) are mixed cultures of two kinds of innate immune cells, namely natural killer cells (NK cells) and gamma delta T cells (γδT cells), which are co-activated and co-cultured ex-vivo in a certain proportion by the unique TKC technology. Adoptive TKC transfer is expected to exert a strong anti-tumor effect through synergistic action between NK cells and γδT cells. In this study, the safety, tolerance, and preliminary efficacy of adoptive TKC transfer combined with chemotherapy will be examined in patients with advanced NSCLC.

Descripción general del estudio

Estado

Reclutamiento

Condiciones

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

Intervencionista

Inscripción (Anticipado)

20

Fase

  • Fase 1

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

  • Nombre: Haichuan Su
  • Número de teléfono: 18629190366
  • Correo electrónico: suhc@fmmu.edu.cn

Ubicaciones de estudio

    • Shanxi
      • Xi'an, Shanxi, Porcelana, 710038
        • Reclutamiento
        • Tangdu Hospital, Fourth Military Medical University
        • Contacto:
          • Haichuan Su
          • Número de teléfono: 18629190366
          • Correo electrónico: suhc@fmmu.edu.cn

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años a 70 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  1. Aged≥18 years old and ≤70 years old when signing the informed consent; regardless of gender;
  2. Body weight>40kg;
  3. Histopathology or cytology confirmed as advanced NSCLC which is not suitable for radical surgical resection;
  4. 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).
  5. Imaging examination showed no tumor thrombus in the portal vein/inferior vena cava;
  6. 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;
  7. Prothrombin time (PT)/international normalized ratio (INR) <1.5 ULN and partial thromboplastin time (PTT)/activated partial thromboplastin time (APTT) <1.5 ULN;
  8. 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;
  9. Women of child-bearing age must be negative for pregnancy test at 7 days before initiation of the treatment.
  10. Eastern Cooperative Oncology Group (ECOG) scores≤1.
  11. Expected survival no less than 6 months.

Exclusion Criteria:

  1. History of any chemotherapy within 2 weeks before a single blood collection;
  2. Participating in other clinical trials in the past 30 days;
  3. Current on systemic steroid or steroid inhalers;
  4. Active brain metastasis or spinal cord compression
  5. Uncontrollable pleural and peritoneal effusion requiring clinical treatment or intervention;
  6. Active bleeding, and thrombotic diseases requiring treatment;
  7. 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;
  8. 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;
  9. Allergic diathesis and allergic to immunotherapy or relevant drugs;
  10. Pregnancy or lactation;
  11. 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;
  12. 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);
  13. Any mental diseases, including dementia and changes in mental status that may influence the understanding about the informed consent and questionnaire;
  14. Judged as serious uncontrollable diseases by the researchers, or other conditions that may interfere with the treatment and therefore being ineligible.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿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)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
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.
Standard chemotherapy drug
TKC: co-cultured autologous NK cells and γδT cells

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Safety evaluation by the incidence of adverse events (AEs) and serious adverse events (SAEs)
Periodo de tiempo: 24 months
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).
24 months

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Overall response rate (ORR)
Periodo de tiempo: 24 months
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).
24 months
Duration of response (DOR)
Periodo de tiempo: 24 months
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).
24 months
Progression-free survival (PFS)
Periodo de tiempo: 24 months
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.
24 months

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Colaboradores

Investigadores

  • Silla de estudio: Helong Zhang, IEC of Institution for National Drug Clinical Trials ,Tangdu Hospital

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Anticipado)

8 de agosto de 2021

Finalización primaria (Anticipado)

8 de agosto de 2022

Finalización del estudio (Anticipado)

30 de noviembre de 2023

Fechas de registro del estudio

Enviado por primera vez

16 de julio de 2021

Primero enviado que cumplió con los criterios de control de calidad

26 de julio de 2021

Publicado por primera vez (Actual)

4 de agosto de 2021

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

4 de agosto de 2021

Última actualización enviada que cumplió con los criterios de control de calidad

26 de julio de 2021

Última verificación

1 de julio de 2021

Más información

Términos relacionados con este 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.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .