CD19-CAR_Lenti T Cells in Pediatric Patients Affected by Relapsed/Refractory CD19+ ALL and DLBCL or PML
Phase I/II Study of Anti-CD19 Chimeric Antigen Receptor-Expressing T Cells in Pediatric Patients Affected by Relapsed/Refractory CD19+ Acute Lymphoblastic Leukemia and Diffuse Large B Cell Lymphoma (DLBCL) or Primary Mediastinal B Cell Lymphoma (PML)
調査の概要
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
研究連絡先
- 名前:Franco Locatelli, MD, PhD
- 電話番号:2678 0039 066859
- メール:franco.locatelli@opbg.net
研究連絡先のバックアップ
- 名前:Francesca del Bufalo, MD
- 電話番号:2739 0039 066859
- メール:francesca.delbufalo@opbg.net
研究場所
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Roma、イタリア、00165
- 募集
- IRCCS Ospedale Pediatrico Bambino Gesù
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コンタクト:
- Franco Locatelli, MD, PhD
- 電話番号:2678 0039 066859
- メール:franco.locatelli@opbg.net
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コンタクト:
- Francesca del Bufalo, MD
- 電話番号:2739 0039 066859
- メール:francesca.delbufalo@opbg.net
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主任研究者:
- Franco Locatelli, MD, PhD
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主任研究者:
- Francesca del Bufalo, MD
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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:
Diagnosis of CD19 expressing B-ALL or DLBCL or PML and one of the following:
- Patients in 1st relapse, with High-Risk (HR) features including: MLL- rearrangements, E2A/TCF3-PBX1, TCF3-HLF [t(17;19)], hypodiploidy (i.e., <44 chromosomes), TP53 alterations, early (i.e., <30 months from diagnosis)/very early (i.e., <18 months from diagnosis) isolated or combined bone marrow relapse
- MRD > 0.1% after either reinduction therapy or any course of consolidation for relapsed ALL
- Patients with DLBCL or PML in 1st or subsequent relapse, after at least one standard frontline chemotherapy
- Age: 1 year - 25 years for Bcp-ALL and 1-35 years for B-NHL.
- Voluntary informed consent is given. For subjects < 18 year-old their legal guardian must give informed consent. Pediatric subjects will be included in age-appropriate discussion and verbal assent will be obtained for those greater than or equal to 12 years of age, when appropriate.
- Clinical performance status: Patients > 16 years of age: Karnofsky greater than or equal to 60%; Patients < 16 years of age: Lansky scale greater than or equal to 60%.
- Patients of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen.
- Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.
Exclusion Criteria:
- Pregnant or lactating women
- Severe, uncontrolled active infections
- HIV, or active HCV and/or HBV infection (detection of viral RNA/DNA in blood)
- Life-expectancy < 6 weeks
- Hepatic function: Inadequate liver function defined as total bilirubin > 4x upper limit of normal (ULN) or transaminase (ALT and AST) > 6 x ULN
- Renal function: serum creatinine > 3x ULN for age.
- Blood oxygen saturation < 90%.
- Cardiac function: Left ventricular ejection fraction lower than 45% by ECHO.
- Congestive heart failure, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the subject.
- BM blasts > 50% pre-infusion.
- Hyperleukocytosis (greater than or equal to 20,000 blasts/microliter) or rapidly progressive disease that in the evaluation of the investigator would compromise ability to complete study therapy
- Presence of active, grade 2-4 acute or moderate-severe chronic GvHD
- Recurrent or refractory ALL with testicular involvement
Concurrent or recent prior therapies, before infusion:
- Systemic steroids (at a dose > 2 mg/kg prednisone) in the 2 weeks before infusion. Recent or current use of inhaled/topical/non-absorbable steroids is not exclusionary.
- Systemic chemotherapy in the week preceding infusion.
- Anti-thymocyte globulin (ATG) in the 4 weeks preceding infusion.
- Immunosuppressive agents in the 1 week preceding infusion.
- Radiation therapy must have been completed at least 3 weeks prior to enrollment.
- Other anti-neoplastic investigational agents currently administered or within 30 days prior to infusion (i.e. start of protocol therapy);
- Exceptions:
i. There is no time restriction with respect to prior intrathecal chemotherapy, provided that there is complete recovery from any acute toxic effects of such; ii. Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study provided that they meet all other eligibility criteria; iii. Subjects receiving steroid therapy at physiologic replacement doses only are allowed provided that there has been no increase in dose for at least 2 weeks prior to starting apheresis;
- Patient-derived CD19-CAR_Lenti production failure: vitality of the fresh product <80%, CD3+ cells <80%, CD3+ CAR+ cells <10%, non-sterility in IPC at day 5, endotoxin contamination (> 5 EU/ml) in IPC at day 5, mycoplasma contamination in IPC at day 5, failure of the visual inspection.
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:CD19-CAR_Lenti
Following lymphodepletion with chemotherapy (fludarabine + cyclophosphamide), patients will be treated with 1.0 to 3.0 x 10^6/kg CD19-Chimeric Antigen Receptor (CAR)_Lenti positive cells as a single dose.
The product will be infused fresh, at the end of manufacturing.
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Fresh peripheral blood mononuclear cells are manufactured to obtain CD19-CAR_Lenti T cell, second generation CAR T cells incorporating the 4-1BB costimulatory domain.
The fresh product is infused following lymphodepletion chemotherapy at a dose of 1.0-3.0x10^6
CAR+ cells/kg.
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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 |
---|---|---|
Phase I - Identification of dose limiting toxicities (DLTs) and recommended dose (RD)
時間枠:4 weeks after CAR T cell infusion
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Toxicity will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale, version 5.0
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4 weeks after CAR T cell infusion
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Phase I - Identification of recommended dose (RD)
時間枠:4 weeks after CAR T cell infusion of the last patient in the last dose level
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The recommended dose of CD19-CAR_Lenti will be defined as the maximum tolerated dose (MTD) or the highest dose studied, if an MTD is not reached.
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4 weeks after CAR T cell infusion of the last patient in the last dose level
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Phase II - Efficacy
時間枠:Up to 6 months after CAR T cell infusion
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Bone marrow morphological and minimal residual disease complete remission rate at day 28 after infusion for BCP-ALL; Overall Response Rate (CR, CRi, PR and SD) at day 28, day 90 and day 180 after CAR T cells infusion
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Up to 6 months after CAR T cell infusion
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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 |
---|---|---|
全生存期間 (OS)
時間枠:2年まで
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2年まで
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Relapse Rate (RR)
時間枠:Up to 2 years
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Up to 2 years
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Disease-Free Survival (DFS)
時間枠:Up to 2 years
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Up to 2 years
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In vivo persistence/expansion of infused CAR T cell
時間枠:Up to 2 years
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Detection of infused CAR T cell in the peripheral and bone marrow blood
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Up to 2 years
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Cytokine profiling
時間枠:Up to 10 days after CAR T cell infusion
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Define serum cytokine profile (Th1/Th2) after T cell infusion and correlation with cytokine release syndrome (CRS)
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Up to 10 days after CAR T cell infusion
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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 (実際)
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
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
- CD19-CAR_Lenti
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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