Pilot Study of Non-Viral, RNA-Redirected Autologous T Cells Engineered to Contain Anti-CD19 Linked to TCR and 4-1BB Signaling Domains in Patients With Refractory or Relapsed Hodgkin Lymphoma
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- Incidence of Treatment-Emergent Adverse Events, defined as NCI CTCAE V4 > Grade 3
研究概览
简要总结
Pilot open-label study to estimate the feasibility, safety and efficacy of intravenously administered, RNA electroporated autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains (referred to as "RNA CART19") in Hodgkin Lymphoma (HL) patients. Subjects will be treated with IV administration of RNA anti-CD19 CAR T cells for a total of six doses over 3 weeks.
详细描述
The study will enroll 10 evaluable patients. Evaluable patients are those who have received at least 1 of the 6 RNA CART19 doses at the protocol-specified level. Important safety data can be collected even if a patient receives only one RNA CART19 dose. Subjects (n = 10) will receive up to six IV doses of 8x105-1.5x106 RNA CART19 cells/kg/dose for subjects<80kg and 1x108 RNA CART19 cells/dose (±20%) for subjects ≥80kg.
The RNA CART19 doses and mid-treatment single dose cyclophosphamide will be administered on Mondays, Wednesdays or Fridays. Dosing can be initiated on any of those days. Subjects will be infused in a staggered fashion at two week intervals; that is, the next subject cannot be infused prior to two weeks since the last infusion of the previous subject.
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 24 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects with HL with no available curative treatment options (such as autologous SCT) who have a limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled.
- •HL with biopsy-proven relapse or refractory disease who are unresponsive to or intolerant of at least one line of standard salvage therapy;
- •Patients must have evaluable disease by radiologic imaging (FDG PET-CT or FDG PET-MRI) within 42 day of enrollment; evaluable includes both assessable and/or measurable disease
- •Age 18 to 24 years. Patients ages 22-24 will only be enrolled if they are currently being treated at CHOP or another pediatric facility/oncologist.
- •Expected survival > 12 weeks at time of screening
- •Adequate organ function defined as:
- •Renal function defined as:
- •Creatinine clearance or radioisotope GFR > 60 mL/min/1.73 m2 OR
- •Serum creatinine: < 1.7mg/dL (male subjects) or < 1.4mg/dL (female subjects)
- •ALT < 5 times the ULN for age
- •Total Bilirubin < 2.0 mg/dl
- •Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation > 94% on room air
- •Patients with relapsed disease after prior allogeneic SCT (myeloablative or non-myeloablative) will be eligible if they meet all other inclusion criteria and
- •Have no active GVHD and require no immunosuppression
- •Are more than 6 months from transplant 6) Karnofsky performance status ≥ 50 at screening
- •Left Ventricular Shortening Fraction (LVSF) > 28% confirmed by echocardiogram, or Left Ventricular Ejection Fraction (LVEF) > 45% confirmed by echocardiogram or MUGA
- •Signed written informed consent must be obtained prior to any study procedures
- •Successful T cell test expansion (to be performed as part of inclusion criteria until 3 subjects meet all enrollment criteria)
排除标准
- •Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum pregnancy test at enrollment. A urine pregnancy test will be performed within 48 hours before the RNA CART19 infusion.
- •Uncontrolled active infection.
- •Active hepatitis B or hepatitis C infection.
- •Any uncontrolled active medical disorder that would preclude participation as outlined.
- •HIV infection.
- •Patients with known active CNS involvement by malignancy. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was >4 weeks before enrollment
- •Patients in complete remission with no evidence by radiologic imaging of disease.
- •History of allergy to murine proteins
- •History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
- •Anti-CD20 monoclonal antibody therapy within the last 3 months, or absence of circulating B cells
- •Unstable angina and/or myocardial infarction within 6 months prior to screening.
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events, defined as NCI CTCAE V4 > Grade 3
时间窗: Month 4 post-CART19 Infusion
Occurrence of study related adverse events, defined as NCI CTCAE V4 \> grade 3 signs/symptoms, laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment at any time from the first cyclophosphamide infusion until Month 4.
次要结局
未报告次要终点