A Multicentric, Exploratory, Non-randomised, Non-controlled, Prospective, Open-label Phase II Study Evaluating Safety and Efficacy of IBU, G-CSF and Plerixafor as Stem Cell Mobilization Regimen in Patients Affected by X-CGD
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Percentage of patients experiencing adverse events
研究概览
简要总结
This is a phase II exploratory study conducted to evaluate the safety and efficacy of the combination of Ibuprofen, G-CSF and Plerixafor as stem cell mobilization regimen in patients affected by X-CGD.
详细描述
We designed a mobilization trial with the aim of collecting a sufficient number of HSPC in X-CGD patients; it is well known that this procedure is challenging for these patients, potentially due to functional defects induced by their chronic inflammatory state.
The combination of G-CSF and Plerixafor is considered state of the art for HSPC harvest in gene therapy trials; we considered to add a non-steroidal inflammatory drug to increase HSPC mobilization and reduce inflammation that could have a role in altering HSPC content.
If this trial confirms the synergistic effect of the three drugs under investigation, such a regimen will be considered for a HSPC mobilization in future gene therapy trial for X-CGD patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Genetic diagnosis of X-CGD
- •18-45 years of age
- •Karnofsky Index > 80 %
- •Adequate cardiac, renal, hepatic and pulmonary function.
- •Negative thrombophilic screen and negative history for previous thrombotic events
- •Written informed consent
排除标准
- •Previous Bone Marrow Transplantation or previous Gene Therapy.
- •Use of other investigational agents within 4 weeks prior to study enrolment (within 6 weeks if use of long-acting agents).
- •Ongoing IFN-γ treatment (within 4 weeks).
- •Symptomatic inflammatory bowel disease.
- •Symptomatic viral, bacterial, or fungal infection within 6 weeks of eligibility
- •Neoplasia (except local skin cancer) or history of "familial" cancer
- •Myelodysplasia or other serious hematological disorder
- •History of uncontrolled seizures and deep venous thrombosis
- •Other systemic disease judged as incompatible with the procedure
- •Positivity for HIV and/or HCV RNA and/or HbsAg and/or HBV DNA
- •Active alcohol or substance abuse within 6 months of the study.
- •Contraindications to IBU, G-CSF, Plerixafor or Pantoprazole administration
研究组 & 干预措施
XCGD mobilization
Treatment with combination of Ibuprofen, Myelostim and Mozobil
干预措施: Mozobil (Drug)
XCGD mobilization
Treatment with combination of Ibuprofen, Myelostim and Mozobil
干预措施: Myelostim (Drug)
XCGD mobilization
Treatment with combination of Ibuprofen, Myelostim and Mozobil
干预措施: Ibuprofen (Drug)
结局指标
主要结局
Percentage of patients experiencing adverse events
时间窗: up to 30 days after the last LP
Percentage of patients experiencing adverse events, as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse events (CTCAe v3.0, 2006) (all grades).
Number of CD34+ collected per body weight after the last LP
时间窗: Day 21-24
Cytofluorimetric analysis for CD34 on PB and on collected PBSC to calculate the number of CD34+ cells collected per kg body weight. The analysis will be performed at the end of the LP(s) (Day 21-24)
次要结局
- DHR (dihydrorhodamine) test in myeloid progeny(Through study completion, an average of 1 year)
- Change in number of CD34+ cells in PB before and after administration of Ibuprofen(Day 6 and day 7)
- Functional characterization of mobilized CD34+ cells.(Through study completion, an average of 1 year)
- Transduction efficiency(Through study completion, an average of 1 year)
研究者
Ciceri Fabio
Director Hematology and BMT Unit
IRCCS San Raffaele