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)
調査の概要
状態
状態
条件
条件
介入・治療
介入・治療
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
研究の種類
入学 (予想される)
入学
段階
段階
- フェーズ 1
連絡先と場所
研究連絡先
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
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-
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
適格基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
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
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)
アーム数
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・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
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
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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
|
二次結果の測定
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).
|
24 months
|
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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).
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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.
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24 months
|
協力者と研究者
協力者
協力者
捜査官
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
主要日程の研究
研究開始 (予想される)
研究開始
一次修了 (予想される)
一次修了
研究の完了 (予想される)
研究の完了
試験登録日
最初に提出
最初に提出
QC基準を満たした最初の提出物
QC基準を満たした最初の提出物
最初の投稿 (実際)
最初の投稿
学習記録の更新
投稿された最後の更新 (実際)
投稿された最後の更新
QC基準を満たした最後の更新が送信されました
QC基準を満たした最後の更新が送信されました
最終確認日
最終確認日
詳しくは
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