Treatment of Relapsed and/or Chemotherapy Refractory CD33 Positive Acute Myeloid Leukemia by CART-33 (CART33)
Clinical Study of Chimeric CD(Cluster of Differentiation)33 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Acute Myeloid Leukemias
RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells.
PURPOSE: This clinical trial is to study genetically engineered lymphocyte therapy in treating patients with CD33 positive acute myeloid leukemias that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to further chemotherapy.
調査の概要
状態
詳細な説明
PRIMARY OBJECTIVES:
I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD33 vector (referred to as CART-33 cells).
II. Determine duration of in vivo survival of CART-33 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of CART-33 TCR zeta:CD137 and TCR (T-cell receptor) zeta cells over time.
SECONDARY OBJECTIVES:
I. For patients with detectable disease, measure anti-leukemia response due to CART-33 cell infusions.
II. To determine if the CD137 transgene is superior to the TCR zeta only transgene as measured by the relative engraftment levels of CART-33 TCR zeta:CD137 and TCR zeta cells over time.
III. Estimate relative trafficking of CART-33 cells in bone marrow.
IV. For patients with stored or accessible leukemia blasts, determine leukemia cell killing by CART-33 cells in vitro.
V. Determine if cellular or humoral host immunity develops against the murine anti-CD33, and assess correlation with loss of detectable CART-33 (loss of engraftment).
VI. Determine the relative subsets of CART-33 T cells (Tcm, Tem, and Treg).
OUTLINE: Patients are assigned to 1 group according to order of enrollment.
Patients receive anti-CD33-CAR (coupled with CD137 and CD3 zeta signalling domains)vector-transduced autologous T cells on days 0,1, and 2 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed intensively for 6 months, every 3 months for 2 years, and annually thereafter for 13 years.
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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Beijing
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Beijing、Beijing、中国、100853
- 募集
- Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital, Hematological Department, Affiliated Hospital of Changzhi Medical College
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コンタクト：
- Xuliang Shen, Dr.
- 電話番号：86-355-13015365546
- メール：shenxlcyp@sohu.com
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副調査官：
- Ying Liu, Dr.
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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:
Male and female subjects with CD33+ acute myeloid leukemia in patients with no available curative treatment options (such as autologous or allogeneic SCT) who have limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled
- CD33+ acute myeloid leukemia CR can not be achieved after at least 2 prior combination chemotherapy regimens.
AML in CR(complete remission)2 or CR3 and not eligible for allogeneic SCT because of age, comorbid disease, or lack of available family member or unrelated donor.
Less than 1 year between last chemotherapy and progression (i.e. most recent progression free interval < 1 year).
Relapsed after prior autologous or allogenic SCT. AML patients with relapsed or residual disease after at least 1 prior therapy and not eligible for allogeneic SCT.
Residual disease after primary therapy and not eligible for autologous SCT
- Expected survival > 12 weeks
- Creatinine < 2.5 mg/dl
- ALT(alanine aminotransferase)/AST (aspartate aminotransferase)< 3x normal
- Bilirubin < 2.0 mg/dl
- Any relapse after prior SCT will make patient eligible regardless of other prior therapy
- Adequate venous access for apheresis, and no other contraindications for leukapheresis
- Voluntary informed consent is given
Exclusion Criteria:
Pregnant or lactating women
- The safety of this therapy on unborn children is not known
- Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
- Uncontrolled active infection
- Active hepatitis B or hepatitis C infection
- Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
- Previously treatment with any gene therapy products
- Feasibility assessment during screening demonstrates < 30% transduction of target lymphocytes, or insufficient expansion (< 5-fold) in response to CD3/CD137 costimulation
- Any uncontrolled active medical disorder that would preclude participation as outlined
- HIV infection
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：anti-CD33 CAR T cells
Patients receive anti-CD33-CAR retroviral vector-transduced autologous or donor-derived T cells on days 0,1, 2 in the absence of disease progression or unacceptable toxicity.
|
genetically modified lymphocyte therapy
他の名前：
他の名前：
|
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 |
|---|---|---|
|
研究関連の有害事象の発生
時間枠：24週目まで
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>= グレード 3 の徴候/症状、実験室毒性、および臨床事象として定義される）であり、研究治療に関連している可能性がある、可能性が高い、または確実に関連している
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24週目まで
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二次結果の測定
結果測定 |
時間枠 |
|---|---|
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Anti-leukemia responses to CART-33 cell infusions
時間枠：up to 24 weeks
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up to 24 weeks
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その他の成果指標
結果測定 |
時間枠 |
|---|---|
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in vivo existence of CART33
時間枠：1 year
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1 year
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協力者と研究者
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
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 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
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
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- CHN-PLAGH-BT-006
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