CAR T-cell Therapy Directed to CD70 for Pediatric Patients With Hematological Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose of CD70-CAR T cells
研究概览
简要总结
The study participant has one of the following blood cancers: acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS), acute lymphoblastic leukemia (B-ALL, T-ALL) or Lymphoma. Your cancer has been difficult to treat (refractory) or has come back after treatment (relapse).
Primary Objective
To determine the safety and maximum tolerated dose of intravenous infusions of escalating doses of CD70-CAR T cells in patients (≤21 years) with recurrent/refractory CD70+ hematological malignancies after lymphodepleting chemotherapy.
Secondary Objectives
To evaluate the antileukemic activity of CD70-CAR T cells. We will determine the anti- leukemic activity of the CD70-CAR T cells in the bone marrow and in the treatment of extramedullary disease.
详细描述
The primary interventions are a lymphodepleting chemotherapy regimen (fludarabine and cyclophosphamide), followed by a single autologous infusion of CD70-CAR T cells.
Phase I study evaluating three (3) dose levels of CD70-CAR T cells.
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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≤21 years old
- •Relapsed/refractory CD70+ hematological malignancy
- •Relapsed disease: Patients developing recurrent disease after a prior complete remission (CR)
- •Refractory disease: Patients with persistent disease despite 3 cycles of induction chemotherapy.
- •Relapsed/refractory CD70+ AML or MDS:
- •Relapsed disease that is CD70 positive
- •Refractory disease that is persistent despite 3 cycles of chemotherapy
- •Relapsed/refractory CD70+ B-cell ALL:
- •Relapsed disease that is CD70 positive and CD19 negative/dim or patients otherwise ineligible for CD19-directed therapies including:
- •Patients in 2nd or greater relapse
- •Patients with relapse after allogeneic HSCT
- •Relapsed/refractory CD70+ T-cell ALL:
- •Relapsed /refractory disease that is CD70 positive
- •Mixed Phenotype Acute Leukemia (MPAL):
- •Relapsed/refractory that is CD70 positive
- •Relapsed/refractory CD70+ lymphoma:
- •Relapsed disease that is CD70 positive and CD19 negative/dim or patients otherwise ineligible for CD19-directed therapies including:
- •Patients in 2nd or greater relapse
- •Patients with relapse after allogeneic HSCT
- •Estimated life expectancy of >12 weeks
- •Karnofsky or Lansky (age- dependent) performance score ≥50
- •Patients with a history of prior allogeneic HCT must be clinically recovered from prior HCT therapy, have no evidence of active GVHD and have not received a donor lymphocyte infusion (DLI) within the 28 days prior to apheresis
- •Patient must have an identified HCT donor
- •For females of childbearing age:
- •i. Not lactating with intent to breastfeed
- •ii. Not pregnant with negative serum or urine pregnancy test within 7 days prior to enrollment
排除标准
- •Known primary immunodeficiency
- •Known history of HIV positivity
- •Severe intercurrent bacterial, viral or fungal infection
- •History of hypersensitivity to cornstarch or hydroxyethyl starch
- •Patients with acute promyelocytic leukemia (APL)
- •Known contraindication to protocol defined lymphodepleting
- •chemotherapy regimen of Fludarabine/cyclophosphamide
研究组 & 干预措施
CD70- CAR T cell Therapy
Patients will receive autologous (their own) cells.
干预措施: Fludarabine (Drug)
CD70- CAR T cell Therapy
Patients will receive autologous (their own) cells.
干预措施: Cyclophosphamide (Drug)
CD70- CAR T cell Therapy
Patients will receive autologous (their own) cells.
干预措施: CD70-CAR T cell infusion (Autologous) (Drug)
CD70- CAR T cell Therapy
Patients will receive autologous (their own) cells.
干预措施: Mesna (Drug)
结局指标
主要结局
Maximum tolerated dose of CD70-CAR T cells
时间窗: 28 days after CD70-CAR T-cell infusion
Phase I design to determine the maximum tolerated dose (MTD) of autologous, CD70-CAR T cells. Three (3) dose levels will be evaluated (1x10e6, 3x10e6, and 1x10e7 cells/kg).
次要结局
未报告次要终点