Clinical Trial Phase I / II to Evaluate the Safety and Efficacy of the Infusion of Autologous CD34 + Cells Transduced With a Lentiviral Vector Carrying the Gene FANCA in Patients With FA Subtype A (FANCOLEN-1)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
研究概览
简要总结
This is an open, Phase I / II clinical trial to evaluate the safety and efficacy of a hematopoietic gene therapy procedure with an orphan drug consisting of a lentiviral vector carrying the FANCA gene for patients with Fanconi Anemia of Subtype A .
CD34 + cells derived from bone marrow and / or mobilized peripheral blood (fresh and / or cryopreserved) from patients with Fanconi subtype A (FA-A), will be transduced ex vivo with a lentiviral vector carrying the gene FANCA (orphan drug) . After transduction the cells will be inoculated in patients in order to restore their hematopoiesis with genetically corrected stem cells.
详细描述
The main objective of this open-label Phase I / II clinical trial is to evaluate the safety and therapeutic efficacy of a hematopoietic gene therapy procedure with an orphan drug consisting of a lentiviral vector carrying the FANCA gene for patients with Fanconi's Anemia Subtype A.
The drug to be administered to the patients consists of the cellular product resulting from the transduction of autologous CD34 + cells with the therapeutic lentiviral vector PGK-FANCA.Wpre *.
The dose of cells to infuse in the patients will be that obtained from the transduction process of between 3x10^5 and 4x10^6 CD34 + cells / kg of patient body weight.
The cells will be infused intravenously in a single dose, after complete the transduction process.
Follow-up period: 3 years after infusion of transduced cells. However, patients will be monitored outside the clinical trial over a 10-year period.
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 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with Fanconi Anemia complementation group A (FA-A)
- •Minimum age 1 year
- •Maximum age 21 years
- •Lansky Index> 60%.
- •Informed consent in accordance with current legal regulations.
- •Number of cells to be transduced: At least 3x10^5 purified CD34+ / kg body weight.
- •Negative result in the urine pregnancy test at the baseline visit for women of childbearing age, who should be committed to using an effective contraceptive method during the period of study participation.
排除标准
- •Patients with an human leukocyte antigen (HLA) identical family donor.
- •Evidence of myelodysplastic syndrome or leukemia, or cytogenetic abnormalities predicting the same in bone marrow aspirates. In this case, the studies carried out two months in advance of the patient's entry into the clinical trial will be considered valid.
- •Evidence that the patient to be infused has signs of somatic mosaicism, with hematologic improvement.
- •Any illness or concomitant process that in the opinion of the investigator incapacitates the subject for their participation in the study.
- •Pre-existing sensory or motor impairment> = grade 2 according to the National Cancer Institute (NCl) criteria.
- •Pregnant or lactating women.
研究组 & 干预措施
Autologous CD34+ cells transducted with PGK-FANCA-Wpre *
CD34 + cells from patients with Fanconi subtype A (FA-A) transduced ex vivo with lentiviral vector carrying the gene FANCA, PGK-FANCA-Wpre*The product to be infused consist of a suspension of transduced CD34^+ cells.
干预措施: IV administration of Genetically Engineered Hematopoietic Stem/Progenitors Cells (HSPCs) (Procedure)
Autologous CD34+ cells transducted with PGK-FANCA-Wpre *
CD34 + cells from patients with Fanconi subtype A (FA-A) transduced ex vivo with lentiviral vector carrying the gene FANCA, PGK-FANCA-Wpre*The product to be infused consist of a suspension of transduced CD34^+ cells.
干预措施: Genetically Engineered Hematopoietic Stem/Progenitor Cells (Biological)
Autologous CD34+ cells transducted with PGK-FANCA-Wpre *
CD34 + cells from patients with Fanconi subtype A (FA-A) transduced ex vivo with lentiviral vector carrying the gene FANCA, PGK-FANCA-Wpre*The product to be infused consist of a suspension of transduced CD34^+ cells.
干预措施: Laboratory Biomarker Analysis (Other)
Autologous CD34+ cells transducted with PGK-FANCA-Wpre *
CD34 + cells from patients with Fanconi subtype A (FA-A) transduced ex vivo with lentiviral vector carrying the gene FANCA, PGK-FANCA-Wpre*The product to be infused consist of a suspension of transduced CD34^+ cells.
干预措施: Filgrastim (Biological)
Autologous CD34+ cells transducted with PGK-FANCA-Wpre *
CD34 + cells from patients with Fanconi subtype A (FA-A) transduced ex vivo with lentiviral vector carrying the gene FANCA, PGK-FANCA-Wpre*The product to be infused consist of a suspension of transduced CD34^+ cells.
干预措施: Plerixafor (Drug)
Autologous CD34+ cells transducted with PGK-FANCA-Wpre *
CD34 + cells from patients with Fanconi subtype A (FA-A) transduced ex vivo with lentiviral vector carrying the gene FANCA, PGK-FANCA-Wpre*The product to be infused consist of a suspension of transduced CD34^+ cells.
干预措施: Bone Marrow Aspiration (Procedure)
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
时间窗: Up to 3 years after infusion of transduced cells
All adverse events will be registered for 3 years from infusion of transduced cells
Proportion of patients with at least 0.1 copy of the therapeutic vector per nucleated bone marrow or peripheral blood cells two years after infusion.
时间窗: 2 years after infusion of transduced cells
Detection of at least 0.1 copy of the therapeutic vector per nucleated bone marrow cell or peripheral blood cells two years after infusion.
次要结局
- Proportion of patients with clinical hematological response after the infusion of autologous CD34 + cells transduced with the therapeutic lentiviral vector(2 years after infusion of transduced cells)
研究者
Julian Sevilla
M.D.PhD Specialist in Hematology Hemotherapy, Responsible for the Transfusion Service and Unit for the Obtention and Processing of Hematopoietic Progenitors and other cellular therapies at the Hospital Infantil Universitario Niño Jesús de Madrid.
Hospital Infantil Universitario Niño Jesús, Madrid, Spain