Consolidation Therapy With Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19 in Patients With Chronic Lymphocytic Leukemia Following Upfront Chemotherapy With Pentostatin, Cyclophosphamide and Rituximab
2019年1月9日 更新者:Memorial Sloan Kettering Cancer Center
A Phase I Trial of Consolidation Therapy With Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19 in Patients With Chronic Lymphocytic Leukemia Following Upfront Chemotherapy With Pentostatin, Cyclophosphamide and Rituximab
The purpose of this Phase I study is to test the safety and effect of specially prepared cells collected from the patients called "modified T cells."
We want to find a safe dose of modified T cells for patients who have disease remaining after initial chemotherapy.
We also want to find out what effects these T cells have on you and your leukemia.
研究概览
研究类型
介入性
注册 (实际的)
13
阶段
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
-
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New York
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New York、New York、美国、10065
- Memorial Sloan Kettering Cancer Center
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参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- CLL patients with evidence of residual disease, who have achieved PR, nPR or CR with detectable MRD following upfront therapy consisting of pentostatin, cyclophosphamide and rituximab.
- The presence of MRD will be assessed by the flow cytometry and polymerasechain reaction at the MSKCC Diagnostic Molecular Pathology Laboratory.
- Age ≥ 18 years of age.
- Creatinine ≤2.0 mg/100 ml, bilirubin ≤2.0 mg/100 ml, AST and ALT ≤3.0x normal, PT and PTT ≤2x normal outside the setting of stable chronic anticoagulation therapy, absolute neutrophil count ≥500/mm3, platelets ≥50,000/mm3, hemoglobin ≥8.0g/dl with transfusion support.
- Adequate pulmonary function as assessed by ≥92% oxygen saturation on room air by pulse oximetry.
Exclusion Criteria:
- Karnofsky performance status <70.
- Pregnant or lactating women. Women and men of childbearing age should use effective contraception while on this study and continue for 1 year after all treatment is finished.
- Impaired cardiac function (LVEF <40%) as assessed by ECHO or MUGA scan.
- Patients previously treated with allogeneic bone marrow or stem cell transplantation are ineligible.
- Patients who are immediate candidates for allogeneic bone marrow or stem cell transplantation. Patients who refuse this option remain eligible and need to be documented as such in patient medical record.
- CLL patients with transformed disease (Richter's transformation) are ineligible for enrollment on this study.
- Patients with following cardiac conditions will be excluded:
- New York Heart Association (NYHA) stage III or IV congestive heart failure
- Myocardial infarction ≤6 months prior to enrollment
- History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
- History of severe non-ischemic cardiomyopathy with EF ≤20%
- Patients with HIV and active hepatitis B or hepatitis C infection are ineligible.
- Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation, with the exception of squamous and basal cell carcinoma of skin.
STEP 2 REGISTRATION (Treatment):
The following additional criteria must be met in order for a patient to be eligible to receive the modified T cell infusion. These labs are to be obtained within 2 weeks of T cell infusion.
- Creatinine ≤2.0 mg/100 ml, bilirubin ≤2.0 mg/100 ml, AST and ALT ≤3.0x normal, PT and PTT ≤2x normal outside the setting of stable chronic anticoagulation therapy, absolute neutrophil count ≥500/mm3, platelets ≥50,000/mm3, hemoglobin ≥8.0g/dl with transfusion support.
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
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:consolidative therapy with autologous T cells genetically
A phase I trial of consolidation therapy with autologous T cells genetically targeted to the B cell specific antigen CD19 for patients with chronic lymphocytic leukemia following upfront chemotherapy with pentostatin, cyclophosphamide and rituximab.
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Patients will first receive a single infusion of therapy conditioning with cyclophosphamide.
followed by consolidative therapy with the modified T cells in 3 planned cohorts.
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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 |
|---|---|---|
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toxicity
大体时间:2 years
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Criteria for toxicity: Toxicity will be graded on a scale of 1 to 5 as described by the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 3.0
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2 years
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maximum tolerated dose (MTD)
大体时间:2 years
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If none of the initial 3 patients in a cohort experience a dose limiting toxicity (DLT) then the next dose level will be studied in another cohort of 3 patients
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2 years
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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disease response
大体时间:2 years
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The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow.
Radiographic studies are not required but those that were abnormal pre-treatment will be repeated to document the degree of maximal response.
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2 years
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change in cellular and cytokine tumor microenvironment
大体时间:2 years
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Cellular tumor microenvironment analysis: The presence of regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs), as well as the presence of immune effector cells including dendritic cells, NK cells, and effector T cells will be assessed by fluorescence-activated cell sorting (FACS).
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2 years
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the impact of infused modified T cells
大体时间:2 years
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Persistence of gene-modified T cells is defined by the presence of any percentage of detectable cells.
The percentage of gene-modified T cells/ total T cells will be recorded for all patients treated at each dose level.
In addition, gene-modified T cells will be measured daily for two days, weekly for eight weeks and monthly for six months (by FACS and RT-PCR).
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2 years
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2011年8月22日
初级完成 (实际的)
2019年1月7日
研究完成 (实际的)
2019年1月7日
研究注册日期
首次提交
2011年8月12日
首先提交符合 QC 标准的
2011年8月12日
首次发布 (估计)
2011年8月15日
研究记录更新
最后更新发布 (实际的)
2019年1月11日
上次提交的符合 QC 标准的更新
2019年1月9日
最后验证
2019年1月1日
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.