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

26 juillet 2021 mis à jour par: 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.

Aperçu de l'étude

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Anticipé)

20

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Lieux d'étude

    • Shanxi
      • Xi'an, Shanxi, Chine, 710038
        • Recrutement
        • Tangdu Hospital, Fourth Military Medical University
        • Contact:

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 70 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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 d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Safety evaluation by the incidence of adverse events (AEs) and serious adverse events (SAEs)
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Overall response rate (ORR)
Délai: 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)
Délai: 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)
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Les enquêteurs

  • Chaise d'étude: Helong Zhang, IEC of Institution for National Drug Clinical Trials ,Tangdu Hospital

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Anticipé)

8 août 2021

Achèvement primaire (Anticipé)

8 août 2022

Achèvement de l'étude (Anticipé)

30 novembre 2023

Dates d'inscription aux études

Première soumission

16 juillet 2021

Première soumission répondant aux critères de contrôle qualité

26 juillet 2021

Première publication (Réel)

4 août 2021

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

4 août 2021

Dernière mise à jour soumise répondant aux critères de contrôle qualité

26 juillet 2021

Dernière vérification

1 juillet 2021

Plus d'information

Termes liés à cette étude

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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