子宮頸がんに対する遺伝子操作された免疫エフェクター
遺伝子操作された抗原特異的免疫エフェクター (EIE) を使用した子宮頸がんの革新的な治療
The primary objective of this study is to evaluate the safety of cervical cancer specific engineered immune effectors (CC-EIEs). The secondary objectives are to evaluate the rate of successful CC-EIE generation in vitro and determine the anti-CC efficacy.
調査の概要
詳細な説明
Cervical cancer (CC) is a cancer arising from the cervix. Human papillomavirus (HPV) infection causes more than 90% of the cases. Other risk factors include smoking, a weak immune system, birth control pills, starting sex at a young age, and having many sexual partners, but these are less important. Worldwide, CC is both the fourth-most common cause of cancer and the fourth-most common cause of death from cancer in women. The treatment of CC consists of surgical intervention, radiation, chemotherapy and immunotherapy.
Adoptive immunotherapy with cytotoxic T lymphocytes reactive with specific viral antigens has proven to be effective. Here, the investigators aim to evaluate the safety and efficacy of multiple infusions of CC-specific engineered immune effectors including cytotoxic T lymphocytes in patients.
研究の種類
入学 (実際)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究場所
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-
Guangdong
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Shenzhen、Guangdong、中国、518000
- Shenzhen Geno-immune Medical Institute
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参加基準
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:
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Written, informed consent obtained prior to any study-specific procedures.
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Age older than 10 years.
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Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.
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Expected survival ≥ 12 weeks.
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Not pregnant, and on appropriate birth control if of childbearing potential.
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Evidence of high-risk HPV infection.
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Stage III-IV or recurrent cervical cancer.
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Initial hematopoietic reconstitution with
- neutrophils (ANC) ≥ 1,000/mm^3;
- platelet (PLT) ≥ 100,000/mm^3.
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Proper renal and hepatic functions (ULN denotes "upper limit of normal range") with
- serum creatinine ≤ 2×ULN;
- serum bilirubin ≤ 2×ULN;
- AST/ALT ≤ 2×ULN;
- ALKP ≤ 5×ULN;
- serum bilirubin. 2.0 is acceptable in the setting of known Gilbert's syndrome.
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Human immunodeficiency virus (HIV) and Hepatitis C virus (HCV) test negative.
Exclusion Criteria:
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Patients with
- cervical benign lesions: cervical columnar epithelium ectopic, cervical polyps, cervical endometriosis and cervical tuberculous ulcers;
- cervical benign tumors: cervical submucous myoma, cervical cancer, cervical papilloma.
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Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure (prior, current or planned treatment).
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Previous exposure to mouse SCC antibody.
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Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug or previous participation in this study.
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Minor surgical procedures within 2 days prior to Day 0 (including central venous access device placement for chemotherapy administration, tumor biopsies, needle aspirations).
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Pregnant or lactating females.
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Inadequate bone marrow function with
- absolute neutrophil count < 1,000/mm^3;
- platelet count < 100,000/mm^3;
- Hb < 9 g/dL.
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Inadequate liver and renal function with
- serum (total) bilirubin > 1.5 x ULN;
- AST & ALT > 2.5 x ULN (> 5 x ULN in patients with liver metastases);
- alkaline phosphatase > 2.5 x ULN;
- serum creatinine >2.0 mg/dl (> 177 μmol/L);
- urine dipstick for protein uria should be < 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hour urine collection and must demonstrate < 1 g of protein/24 hr.
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Serious active infection requiring i.v. antibiotics at during screening.
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Subject actively infected with HCV (HCV antibody positive), HBV (HBsAg positive), HIV (HIV antibody positive), HTLV (HTLV antibody positive), Treponema pallidum antibody positive or TB culture positive.
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）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：CC-EIEs
Autologous cervical cancer specific engineered immune effectors (EIEs) |
2 to 4 infusions, once a week, for 1x10^5~1x10^7 CTLs/kg via IV, abdominal cavity or intratumoral injection each time |
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 of CC-EIEs in patients using CTCAE version 4.0 standard to evaluate the level of adverse events
時間枠：6 months
|
Physiological parameter (measuring cytokine response, fever, symptoms) |
6 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Anti-tumor effects
時間枠：1 year
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Objective response, such as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. |
1 year
|
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Functional analyses of CC-EIEs in vitro
時間枠：4 weeks
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The specificity of CC-EIEs in vitro will be analysed by enzyme-linked immunospot assay (ELISPOT). |
4 weeks
|
協力者と研究者
捜査官
- 主任研究者：Lung-Ji Chang, PhD、Shenzhen Geno-Immune Medical Institute
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
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
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。