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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- maximum tolerated dose (MTD)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Karnofsky performance status <
- •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.
研究组 & 干预措施
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.
干预措施: cyclophosphamide (Drug)
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.
干预措施: modified T cells (Biological)
结局指标
主要结局
maximum tolerated dose (MTD)
时间窗: 2 years
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
toxicity
时间窗: 2 years
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
次要结局
- disease response(2 years)
- change in cellular and cytokine tumor microenvironment(2 years)
- the impact of infused modified T cells(2 years)