NCT04276870招募中2 期
CD19-Directed Chimeric Antigen Receptor CD19 Redirected Autologous T Cells (CART19) for Orphan Indications of Pediatric B Cell Acute Lymphoblastic Leukemia (B ALL)
Stephan Grupp MD PhD2 个研究点 分布在 1 个国家目标入组 133 人开始时间: 2020年3月12日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 133
- 试验地点
- 2
- 主要终点
- Event-free survival (EFS)
研究概览
简要总结
This is an open-label, four-cohort, phase 2 study to determine the efficacy of CART19 in pediatric and young adult patientswith hypodiploid (Cohort A) or t(17;19) B-ALL (Cohort B), infants with very high risk KMT2A B-ALL (Cohort C), and in patients with central nervous system (CNS) relapse who did not receive cranial radiation (XRT) or bone marrow transplantation (BMT) (Cohort D).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 0 Years 至 29 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent form must be obtained prior to any study procedure.
- •Male and female patients with documented CD19+ B-ALL
- •a.Cohort A & B: Patients, regardless their response to initial or relapsed B ALL therapy, with the following characteristics: i.Cohort A: Subjects with confirmation of a hypodiploid karyotype (chromosome number fewer than 45) ii.Cohort B: Subjects with cytogenetic confirmation of the chromosomal translocation t(17;19) (Cohort B) b.Cohort C: Infants w/ newly diagnosed KMT2A rearranged B-ALL classified as very high risk by the following criteria: i.Age < 3 months at diagnosis ii.Age < 6 months and WBC > 300,000x109/L at diagnosis or a poor prednisone response in induction iii.MRD positive > 0.01 (or PCR > 104) after 2 courses of standard infant ALL therapy.
- •c.Cohort D: Subjects in a first or greater CNS relapse, prior to therapy with cranial XRT or HSCT for the current relapse
- •Documentation of CD19 tumor expression in bone marrow, peripheral blood, CSF, or tumor tissue.
- •Age 0 to 29 years
- •Adequate organ function defined as:
- •A serum creatinine based on age/gender as follows:
- •Maximum Serum Creatinine (mg/dL) Age Male Female 0 to < 2 years 0.6 0.6 2 to < 6 years 0.8 0.8 6 to < 10 years 1.0 1.0 10 to < 13 years 1.2 1.2 13 to < 16 years 1.5 1.4
- •≥ 16 years 1.7 1.4
- •Adequate liver function:
- •i.ALT≤ 5 x ULN; ALT ii.Total bilirubin ≤ 3 x ULN iii.ALT and/or bilirubin results that exceed this range are acceptable if, in the opinion of the physician-investigator (or as confirmed by liver biopsy), the abnormalities are directly related to ALL infiltration of the liver.
- •c.Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and < Grade 3 hypoxia; DLCO ≥ 40% (corrected for anemia) if PFTs are clinically appropriate as determined by the physician-investigator.
- •d.Left Ventricular Shortening Fraction (LVSF) ≥ 28%, or Left Ventricular Ejection Fraction (LVEF) ≥ 45% by echocardiogram. In cases where quanitative assessment of LVSF/LVEF is not possible, a statement by the cardiologist that the ECHO shows qualititatively normal ventricular function wll suffice.
- •Adequate performance status defined as Lansky or Karnofsky score ≥ 50
- •Subjects of reproductive potential must agree to use acceptable birth control methods
排除标准
- •For subjects with a CNS relapse, prior cranial XRT or BMT for the current relapse is an exclusion.
- •Active hepatitis B or active hepatitis C.
- •HIV Infection.
- •Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
- •Concurrent use of systemic steroids at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
- •CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
- •Pregnant or nursing (lactating) women.
- •Uncontrolled active infection.
研究组 & 干预措施
Subjects with hypodiploid B-ALL
Experimental
干预措施: Murine CART19 (Biological)
Subjects with t(17;19) B-ALL
Experimental
干预措施: Murine CART19 (Biological)
Infant subjects with very high risk KMT2A B-ALL
Experimental
干预措施: Murine CART19 (Biological)
Subjects with central nervous system (CNS) relapse
Experimental
who did not receive cranial radiation (XRT) or bone marrow transplantation (BMT)
干预措施: Murine CART19 (Biological)
结局指标
主要结局
Event-free survival (EFS)
时间窗: One year
1 year event-free survival (EFS), where events include no response, relapse, death due to any cause
次要结局
- EFS Rate 1(One year)
- To further evaluate the safety of CART19 in the target patient populations(One year)
- EFS rate 2(One year)
- Relapse Free survival 4(One year)
- MRD conversion(One year)
- Relapse Free survival 2(One year)
- Relapse Free survival 1(One year)
- Relapse Free survival 3(One year)
研究者
Stephan Grupp MD PhD
Director, Cancer Immunotherapy Program
Children's Hospital of Philadelphia
研究点 (2)
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