Phase I/II Study of Immunotherapy for Advanced CD19+ Chronic Lymphocytic Leukemia, Acute Lymphoblastic Leukemia/Lymphoma and Non-Hodgkin Lymphoma With Defined Subsets of Autologous T Cells Engineered to Express a CD19-Specific Chimeric Antigen Receptor

Fred Hutchinson Cancer Center1 个研究点分布在 1 个国家目标入组 204 人开始时间: 2013年5月22日最近更新: 2022年5月25日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Fred Hutchinson Cancer Center
入组人数: 204
试验地点: 1
主要终点: Death Within 8 Weeks of the Study Cell Infusion Thought to be Definitely or Probably Related to Chimeric Antigen Receptor (CAR) T Cell Therapy

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This phase I/II trial studies the side effects and best dose of laboratory treated T cells to see how well they work in treating patients with chronic lymphocytic leukemia, non-Hodgkin lymphoma, or acute lymphoblastic leukemia that have come back or have not responded to treatment. T cells that are treated in the laboratory before being given back to the patient may make the body build an immune response to kill cancer cells.

详细描述

PRIMARY OBJECTIVES:

I. To evaluate the feasibility and safety of adoptive T cell therapy using ex vivo expanded autologous CD8 positive (+) and CD4+ CD19 chimeric antigen receptor (CAR)-T cells for patients with advanced CD19+ B cell malignancies.

SECONDARY OBJECTIVES:

I. To determine the duration of in vivo persistence of adoptively transferred T cells, and the phenotype of persisting T cells.

II. To determine if adoptively transferred T cells traffic to the bone marrow and function in vivo.

研究设计

研究类型: Interventional
分配方式: Non Randomized
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

•INCLUSIONS FOR SCREENING AND LEUKAPHERESIS
•Patients with CD19 expressing acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL)
•Ability to understand and provide informed consent
•Not human immunodeficiency virus (HIV) infected
•INCLUSIONS FOR CAR-T CELL THERAPY
•Patients with:
•CLL who are beyond first remission and who have failed combination chemoimmunotherapy with regimens containing a purine analogue and anti-CD20 antibody or who were not eligible for such therapy; patients with CLL for whom ibrutinib is now standard first line therapy, must have progressed on ibrutinib; patients with fludarabine refractory disease are eligible; patients may be treated following allogeneic hematopoietic cell transplant (HCT); for the concurrent ibrutinib cohort, patients must agree to continue on or be restarted on ibrutinib and must not have had prior intolerance to ibrutinib that would prevent this; patients managed with prior dose reductions for toxicity will continue at the reduced dose for the remainder of this study
•Indolent NHL or mantle cell NHL who are beyond first remission and previously treated with chemoimmunotherapy or who were not eligible for such therapy; patients who have relapsed following autologous or allogeneic HCT are eligible
•Aggressive NHL such as diffuse large B-cell lymphoma (DLBCL), who have relapsed or have residual disease following treatment with curative intent; patients should have relapsed following, or not be eligible for high-dose therapy and autologous HCT; patients with chemotherapy refractory disease or marrow involvement or comorbidities precluding successful autologous HCT are eligible; patients may be treated following allogeneic HCT
•Patients with CD19 expressing, relapsed or refractory ALL
•Patients with one of the above diagnoses whose disease state does not qualify but who have prognostic indicators that suggest a high risk of progression of disease may be screened and undergo leukapheresis; enrollment for T cell therapy would require meeting the full disease state eligibility
•Confirmation of diagnosis
•Evidence of CD19 expression by immunohistochemistry or flow cytometry on any prior or current tumor specimen or high likelihood of CD19 expression based on disease histology
•Karnofsky performance status >= 60%
•All patients of childbearing potential must be willing to use a contraceptive method before, during, and for at least two months after the T cell infusion
•Ability to understand and provide informed consent

排除标准

•EXCLUSIONS FOR CAR-T CELL THERAPY
•Patients requiring ongoing daily corticosteroid therapy at a dose of > 15 mg of prednisone per day (or equivalent); pulsed corticosteroid use for disease control is acceptable
•Active autoimmune disease requiring immunosuppressive therapy is excluded unless discussed with the Principal Investigator (PI)
•Serum creatinine > 2.5 mg/dL
•Serum glutamic oxaloacetic transaminase (SGOT) > 5 x upper limit of normal
•Bilirubin > 3.0 mg/dL
•Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing; those with a forced expiratory volume in one second (FEV1) of < 50 % of predicted will be excluded
•Diffusing capacity of the lung for carbon monoxide (DLCO) (corrected) < 40% will be excluded
•Significant cardiovascular abnormalities as defined by any one of the following: New York Heart Association (NYHA) class III or IV congestive heart failure, clinically significant hypotension, uncontrolled symptomatic coronary artery disease, or a documented ejection fraction of < 35%
•Uncontrolled active infection

研究组 & 干预措施

NHL (dose dense) dose level 2

Experimental

Patients receive anti-CD19-CAR lentiviral vector-transduced autologous T cells IV over 20-30 minutes on day 0. Treatment may be repeated in no less than 21 days with or without additional lymphodepleting chemotherapy if there is persistent disease in the absence of unacceptable toxicity.

Disease subgroup: NHL Dose level: 2 up to 2x106 EGFR+ cells/kg