GD2/CD56 Bi-specific CAR-T Cell Therapy
GD2/CD56 Bi-specific CAR-T Cells for Cancer Treatment
調査の概要
詳細な説明
Patients with refractory and/or recurrent malignancies have poor prognosis despite complex multimodal therapy; therefore, novel curative approaches are needed. The investigators attempt to use T cells genetically modified to express a 4th generation lentiviral GD2/CD56 bi-specific chimeric antigen receptor (bi-4SCAR-GD2/CD56). The chimeric antigen receptor (CAR) molecules enable the T cells to recognize and kill tumor cells through the recognition of a surface antigen, GD2 or CD56, which is expressed at high levels on tumor cells but not at significant levels on normal tissues.
Disialoganglioside (GD2) is a well-studied tumor associated antigen which is expressed uniformly in nervous system-related tumors but at low levels in normal tissues. Over the past few years, CAR-T therapy against GD2 in tumor has achieved encouraging but modest outcomes. Only a fraction of patients achieved measurable responses. In solid tumors, GD2 CAR-T therapy alone may not be as effective as CAR-T cell therapy in hematological malignancies.
Similar to GD2, the CD56 antigen (NCAM-1) is highly expressed on malignancies with neuronal or neuroendocrine differentiation, including small-cell lung cancer, glioblastoma and neuroblastoma, tumor types for which new therapeutic options are needed. CD56-CAR-T cell therapy has potential for treating patients with aggressive malignancies that are nonresponsive to conventional radiotherapy and chemotherapy, or are unsuitable for hematopoietic stem cell transplantation.
To overcome tumor escape of single target antigen and enhance in vivo CAR-T efficacy, a novel bi-specific GD2/CD56 CAR-T therapy regimen is developed to include booster and consolidation CAR-T applications to target highly-refractory cancer. The aim is to evaluate safety and long term efficacy of the bi-CAR-T therapy strategy in GD2 and/or CD56 positive cancer patients.
研究の種類
入学 (予想される)
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
- 募集
- 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:
- Patients with tumors received standard first-line therapy and have been judged to be non-resectable, metastatic, progressive or recurrent.
- The expression status of GD2 or CD56 antigens in the tumor tissue will be determined for eligibility. Positive expression is defined by GD2 and CD56 antibody staining results based on immunohistochemistry or flow cytometry analyses.
- Body weight greater than or equal to 10 kg.
- Age: ≥1 year and ≤ 75 years of age at the time of enrollment.
- Life expectancy: at least 8 weeks.
Prior Therapy:
There is no limit to the number of prior treatment regimens. Any grade 3 or 4 non-hematologic toxicity of any previous therapy must be resolved to grade 2 or less.
- Participant must not have received hematopoietic growth factors for at least 1 week prior to mononuclear cells collection.
- At least 7 days must have elapsed since the completion of therapy with a biologic agent, selected targeted agent or a metronomic non-myelosuppressive regimen.
- At least 4 weeks must have elapsed since prior therapy that included a monoclonal antibody.
- At least 1 week since any radiation therapy at the time of study entry.
- Karnofsky/jansky score of 60% or greater.
- Cardiac function: Left ventricular ejection fraction greater than or equal to 40/55 percent.
- Pulse Ox greater than or equal to 90% on room air.
- Liver function: defined as alanine transaminase (ALT) <3x upper limit of normal (ULN), aspartate aminotransferase (AST) <3x ULN; serum bilirubin and alkaline phosphatase <2x ULN.
- Renal function: Patients must have serum creatinine less than 3 times upper limit of normal.
- Marrow function: White blood cell count ≥1000/ul, Absolute neutrophil count ≥500/ul, Absolute lymphocyte count ≥500/ul, Platelet count ≥25,000/ul (not achieved by transfusion).
- Patients with known bone marrow metastatic disease will be eligible for study as long as they meet hematologic function criteria, and the marrow disease does not have hematologic toxicity.
- For all patients enrolled in this study, themselves or their parents or legal guardians must sign an informed consent and assent.
Exclusion Criteria:
- Existing severe illness (e.g. significant cardiac, pulmonary, hepatic diseases, etc.) or major organ dysfunction, or greater than grade 2 hematologic toxicity.
- Untreatable central nervous system (CNS) metastasis: Patients with previous CNS tumor involvement that has been treated and is stable for at least 6 weeks following completion of therapy are eligible.
- Previous treatment with other genetically engineered GD2 or CD56-specific CAR T cells.
- Active HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) infection or uncontrolled infection.
- Patients who require systemic corticosteroid or other immunosuppressive therapy.
- Evidence of tumor potentially causing airway obstruction.
- Inability to comply with protocol requirements.
- Insufficient CAR T cells availability.
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 |
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実験的:bi-4SCAR-GD2/CD56 T Cell Therapy for GD2 and/or CD56 positive tumor
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Infusion of bi-4SCAR GD2/CD56 T cells at 10^6 cells/kg body weight via IV
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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 |
---|---|---|
Number of patients with adverse events.
時間枠:6 months
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Determine the toxicity profile the bi-4SCAR GD2/CD56 cells with Common Toxicity Criteria for Adverse Effects version 4.0
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6 months
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
抗腫瘍効果
時間枠:1年
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客観的な完全奏効(CR)は、固形腫瘍の反応評価基準(RECIST)v1.1基準によって評価されます。
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1年
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Anti-tumor effects
時間枠:1 year
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Objective partial response (PR) are assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
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1 year
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The expansion of bi-4SCAR GD2/CD56 T cells
時間枠:1 year
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Scale of CAR copies
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1 year
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The persistence of bi-4SCAR GD2/CD56 T cells
時間枠:1 year
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Scale of tumor burden (for efficacy)
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1 year
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Survival time of the patients
時間枠:3 years
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The progression free survival (PFS) time of the patients treated with the bi-4SCAR GD2/CD56 T cells will be evaluated
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3 years
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Survival time of the patients
時間枠:3 years
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The overall survival (OS) time of the patients treated with the bi-4SCAR GD2/CD56 T cells will be evaluated
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3 years
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協力者と研究者
研究記録日
主要日程の研究
研究開始 (予想される)
一次修了 (予想される)
研究の完了 (予想される)
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。
悪性疾患の臨床試験
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Adelphi Values LLCBlueprint Medicines Corporation完了肥満細胞性白血病 (MCL) | 攻撃的な全身性肥満細胞症 (ASM) | SM w Assoc Clonal Hema Non-mast Cell Lineage Disease (SM-AHNMD) | くすぶり全身性肥満細胞症 (SSM) | 無痛性全身性肥満細胞症 (ISM) ISM サブグループが完全に募集されましたアメリカ