Adoptive TKC Transfer Combined With Chemotherapy for Advanced Non-small Cell Lung Cancer (NSCLC)
2021年7月26日 更新者: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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (予想される)
20
段階
- フェーズ 1
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前:Haichuan Su
- 電話番号:18629190366
- メール:suhc@fmmu.edu.cn
研究場所
-
-
Shanxi
-
Xi'an、Shanxi、中国、710038
- 募集
- Tangdu Hospital, Fourth Military Medical University
-
コンタクト:
- Haichuan Su
- 電話番号:18629190366
- メール:suhc@fmmu.edu.cn
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年~70年 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:なし
- 介入モデル:単一グループの割り当て
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的: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
|
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Safety evaluation by the incidence of adverse events (AEs) and serious adverse events (SAEs)
時間枠: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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Overall response rate (ORR)
時間枠: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).
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24 months
|
|
Duration of response (DOR)
時間枠: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)
時間枠: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
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- スタディチェア:Helong Zhang、IEC of Institution for National Drug Clinical Trials ,Tangdu Hospital
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (予想される)
2021年8月8日
一次修了 (予想される)
2022年8月8日
研究の完了 (予想される)
2023年11月30日
試験登録日
最初に提出
2021年7月16日
QC基準を満たした最初の提出物
2021年7月26日
最初の投稿 (実際)
2021年8月4日
学習記録の更新
投稿された最後の更新 (実際)
2021年8月4日
QC基準を満たした最後の更新が送信されました
2021年7月26日
最終確認日
2021年7月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。