Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-04: A Phase 1 Feasibility and Safety Study of CD22-CAR T Cell Immunotherapy for CD22+ Leukemia and Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 4
- 试验地点
- 2
- 主要终点
- The adverse events associated with one or multiple CAR T-cell product infusions will be assessed
研究概览
简要总结
Patients with relapsed or refractory leukemia often develop resistance to chemotherapy and some patients who relapse following CD19 directed therapy relapse with CD19 negative leukemia. For this reason, the investigators are attempting to use T-cells obtained directly from the patient, which can be genetically modified to express a chimeric antigen receptor (CAR) to CD22, a different protein from CD19, expressed on the surface of the leukemic cell in patients with CD22+ leukemia. The CAR enables the T-cell to recognize and kill the leukemic cell through the recognition of CD22, a protein expressed on the surface of the leukemic cell in patients with CD22+ leukemia. This is a Phase 1 study designed to determine the safety and feasibility of the CAR+ T - cells and the feasibility of making enough to treat patients with CD22+ 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
- 1 Year 至 26 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •First 3 subjects: male and female subjects age ≥ 18 years and < 27 years
- •Subsequent subjects: 12 months of age and <27 years of age at the time of study enrollment
- •Disease status (one of the following):
- •If post-allogeneic hematopoetic cell transplant (HCT): confirmed CD22+ leukemia recurrence, defined as ≥0.01% disease
- •If Relapse/Refractory status with no prior history of allogeneic HCT, one of:
- •2nd or grater marrow relapse, with or without extramedullary disease
- •1st marrow relapse at end of 1st month of re-induction with marrow having ≥0.01% blasts by morphology and/or MPF
- •Primary Refractory, defined as >5% blasts by multi-parameter flow after ≥2 separate induction regimens
- •Subject has indication for HCT but is ineligible, inclusive of persistent minimal residual disease
- •CD22+ Lymphoma refractory or relapsed with no known curative therapies available
- •Asymptomatic from CNS involvement, if present, and have a reasonable expectation that disease burden can be controlled in the interval between enrollment and T-cell infusion. Subjects with significant neurologic deterioration will not be eligible for T-cell infusion until stabilized.
- •Free from active GVHD and off immunosuppressive GVHD therapy for 4 weeks.
- •Lansky or Karnofsky performance score of ≥50
- •Life expectancy of >8 weeks
- •Recovered from acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy
- •≥7 days post last chemotherapy administration (excluding intrathecal or maintenance chemotherapy)
- •≥7 days post last systemic corticosteroid administration
- •No prior virotherapy
- •Adequate organ function
- •Adequate laboratory values
- •Patients of childbearing/fathering potential must agree to use highly effective contraception
- •Signed a written consent
排除标准
- •Presence of active clinically significant CNS dysfunction
- •Pregnant or breastfeeding
- •Unable to tolerate apheresis procedure, including placement of temporary apheresis line if required
- •Presence of active malignancy other than CD22+ leukemia or lymphoma
- •Presence of active severe infection
- •Presence of any concurrent medical condition that would prevent the patient from undergoing protocol-based therapy
- •Presence of primary immunodeficiency/bone marrow failure syndrome
- •Unwilling to participate in 15-year follow-up period that is required if CAR T cell therapy is administered
研究组 & 干预措施
Autologous CD22-specific CAR T-cells expressing EGFRt
干预措施: Patient-derived CD22-specific CAR T-cells also expressing an EGFRt (Biological)
结局指标
主要结局
The adverse events associated with one or multiple CAR T-cell product infusions will be assessed
时间窗: 30 days
The type, frequency, severity, and duration of adverse events will be summarized
The number of successfully and unsuccessfully manufactured and infused CAR T-cell products will be assessed
时间窗: 28 days
Proportion of products successfully manufactured and infused
次要结局
未报告次要终点
研究者
Colleen Annesley
Medical Director, Seattle Children's Therapeutics
Seattle Children's Hospital