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)
研究概览
研究类型
注册 (预期的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习联系方式
- 姓名:Franco Locatelli, MD, PhD
- 电话号码:2678 0039 066859
- 邮箱:franco.locatelli@opbg.net
研究联系人备份
- 姓名:Francesca del Bufalo, MD
- 电话号码:2739 0039 066859
- 邮箱:francesca.delbufalo@opbg.net
学习地点
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Roma、意大利、00165
- 招聘中
- IRCCS Ospedale Pediatrico Bambino Gesù
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接触:
- Franco Locatelli, MD, PhD
- 电话号码:2678 0039 066859
- 邮箱:franco.locatelli@opbg.net
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接触:
- Francesca del Bufalo, MD
- 电话号码:2739 0039 066859
- 邮箱:francesca.delbufalo@opbg.net
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首席研究员:
- Franco Locatelli, MD, PhD
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首席研究员:
- Francesca del Bufalo, MD
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
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.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的: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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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Phase I - Identification of dose limiting toxicities (DLTs) and recommended dose (RD)
大体时间: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)
大体时间: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
大体时间: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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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
总生存期(OS)
大体时间:长达 2 年
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长达 2 年
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Relapse Rate (RR)
大体时间:Up to 2 years
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Up to 2 years
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Disease-Free Survival (DFS)
大体时间: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
大体时间: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
大体时间: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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合作者和调查者
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
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