CD123 Redirected Autologous T Cells for AML
Pilot Study of RNA-Redirected Autologous T Cells Engineered to Contain Anti-CD123 Linked to TCR and 4-1BB Signaling Domains in Patients With Refractory or Relapsed Acute Myeloid Leukemia
調査の概要
状態
研究の種類
入学 (実際)
段階
- 初期フェーズ 1
連絡先と場所
研究場所
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19104
- Abramson Cancer Center of the University of Pennsylvania
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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 or female subjects 18 years of age or older with AML with no available curative treatment options using currently available therapies
- Subjects must have a suitable stem cell donor available who may donate cells if the subject needs to undergo allogeneic HCT. Donor may be matched or mismatched and must be found to be suitable according to the institution's standard criteria.
Subjects with second or subsequent relapse, any relapse refractory to salvage, or with persistent disease after at least two lines of therapy.
a. Subjects with relapsed disease after prior allogeneic HCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and i. Have experienced graft rejection (no evidence of donor cells by STR analysis on 2 occasions separated by at least 1 month), OR: ii. Donor cells are present but there is no active GVHD, subject does not require immunosuppression and is more than 6 months from transplant
- Subjects must have evaluable disease defined as >5% blasts on marrow aspirate or biopsy, extramedullary disease (CNS involvement is prohibited), or at least 20% blasts in the peripheral blood within 2 weeks prior to enrollment. Note: subjects with second or subsequent relapse are considered to have evaluable disease even without meeting the above morphologic criteria if they are found to have persistent recurrent disease-associated molecular or cytogenetic abnormalities.
- Creatinine < 1.6 mg/dl
- ALT/AST must be < 5 x upper limit of normal unless related to disease
- Bilirubin < 2.0 mg/dl, unless subject has Gilbert's syndrome (≤3.0 mg/dL);
- ECOG Performance status 0-2.
- Left ventricular ejection fraction > 40% as confirmed by ECHO/MUGA
- Written informed consent is given.
- Subjects of reproductive potential must agree to use acceptable birth control methods.
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 pregnancy test at enrollment. A urine pregnancy test will be performed within 48 hours before infusion.
- HIV infection.
- Active hepatitis B or hepatitis C infection.
- Concurrent use of systemic steroids or immunosuppressant medications. Recent or current use of inhaled steroids or physiologic replacement with hydrocortisone is not exclusionary.
- Absolute lymphocyte count <500/uL
- Any uncontrolled active medical disorder that would preclude participation as outlined.
- Subjects with signs or symptoms indicative of CNS involvement. A CNS evaluation should be performed as clinically appropriate to rule out CNS involvement.
- Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
- Class III/IV cardiovascular disability according to the New York Heart Association Classification.
- Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system
- Subjects with clinically apparent arrhythmia, or arrhythmias that are not stable on medical management, within 2 weeks of the Screening/Enrollment visit.
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:非ランダム化
- 介入モデル:並列代入
- 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:Cohort 1
The first 3 subjects to receive RNA CART123 cells will receive up to 3 doses of RNA CART123 cells, with no lymphodepleting chemotherapy prior to infusion.
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Given IV
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実験的:Cohort 2
The remaining 12 subjects of the study will receive up to six IV doses of RNA CART123 cells. Subjects in Cohort 2 may be given lymphodepleting chemotherapy 4 days (+/- 1 day) prior to the first CART123 cell infusion (if ALC> 500/uL). Lymphodepleting chemotherapy may be repeated before the fourth dose of RNA CART123 cells (if ALC> 500/uL). Lymphodepleting chemotherapy includes a single dose of cyclophosphamide (1g/m2) Weight used for dosing will be the weight obtained prior to the apheresis procedure Cell numbers are based on CAR+ cells with CAR expression determined by flow cytometry Based on the product release criteria, at least 20% of the total cells will be RNA CART123 cells. Dosing will not be changed for changes in subject weight The indicated doses are +/- 20% to account for manufacturing variability. |
与えられた IV
Given 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 |
時間枠 |
|---|---|
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有害事象の数
時間枠:2年
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2年
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協力者と研究者
捜査官
- 主任研究者:Saar Gill, MD, PhD、Abramson Cancer Center of the University of Pennsylvania
研究記録日
主要日程の研究
研究開始
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 (見積もり)
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
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
- 823175 - UPCC 04415
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
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。