Protocol Title: Safety and Feasibility of Autologous CD34+ Hematopoietic Stem Cells Mobilization and Apheresis in Participants With RUNX1 Familial Platelet Disorder
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 4
- 试验地点
- 2
- 主要终点
- Safety and adverse events (AEs)
研究概览
简要总结
To evaluate the safety and feasibility of collecting hematopoietic stem cells (HSC) in participants with RUNX1-FPD.
详细描述
Primary Objective:
- To evaluate the safety of harvesting HSCs in participants with RUNX1 FPD
Secondary Objective
- To evaluate the feasibility and other relevant information of collecting HSCs from participants with RUNX1 FPD
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants who meet all of the following criteria are eligible to be included in the study:
- •Are aged ≥ 18 to 75 years
- •a. Once a favorable review of safety has been completed by the SMC in 3 participants aged ≥ 18 years, the study will be opened to participants aged ≥ 12 years.
- •Are willing and able to provide informed consent, as appropriate (either directly or through a legally authorized representative [LAR]), as described in Appendix 1, Section 13.1
- •Have a confirmed diagnosis of RUNX1 FPD, verified by a Clinical Laboratory Improvement Amendments (CLIA)-certified genetic sequencing report.
- •Clearance by apheresis team to proceed
- •Have systolic blood pressure ≤ 170 mm Hg and diastolic blood pressure ≤ 95 mmHg
- •Are eligible for HSCT per institution requirements
- •Have a Lansky (age < 16 years)/Karnofsky performance status of ≥ 70 (see Appendix 2, Section 13.2).
- •Are willing and able to comply with protocol-defined contraceptive requirements (see Appendix 3 Section 13.3)
- •Have a platelet count ≥ 50,000/μL for initiation of apheresis, assessed within 24 hours prior to the procedure, or, if < 50,000/μL are administered platelets on the day of the collection
- •a. If the apheresis team decides that a central venous catheter (CVC) is to be placed, platelet count should be ≥ 50,000 prior to catheter placement.
- •Have hemoglobin ≥ 7.5 g/dL as assessed within 24 hours prior to the procedure
排除标准
- •Participants who meet any of the following criteria are excluded from the study:
- •Participants with cognitive impairments and/or any serious unstable pre-existing medical condition or psychiatric disorder that can interfere with safety or with obtaining informed consent or compliance with study procedures.
- •Have uncontrolled bleeding
- •Are using supplemental oxygen
- •Have known severe splenomegaly (≥ 20 cm)
- •Have a diagnosis of MDS or hematologic malignancies, as defined by WHO hematolymphoid tumor classification fifth edition (Khourey et al 2022) hematolymphoid tumor classification fifth edition (Khourey et al 2022)
- •Have recent prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ Note: Cancer treated with curative intent < 5 years previously may be allowed following approval from the study investigator. Cancer treated with curative intent > 5 years previously is allowed.
- •Have any prior or current myeloproliferative or a significant coagulation or immunodeficiency disorder
- •Have advanced liver disease, defined as any of the following:
- •Persistent aspartate transaminase, alanine transaminase, or direct bilirubin value > 5× the upper limit of normal (ULN) at screening
- •Screening prothrombin time (PT) or partial thromboplastin time (PTT) > 1.5× ULN
- •Have had prior HSCT or gene therapy
- •Have history of concomitant sickle cell disease
- •Have been treated with an investigational drug within 30 days of screening or 5 half-lives (whichever is longer)
- •Have a positive test result for HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) at screening
- •Participants with positive hepatitis B core antibody (HbcAb) and/or hepatitis B-e antibody (HbeAb) are eligible provided viral load is negative by quantitative polymerase chain reaction (qPCR).
- •Participants who are positive for anti-hepatitis C antibody are eligible as long as they have a negative HCV viral load by qPCR.
- •Have a positive infectious disease panel at screening for human T-lymphotropic virus 1 or 2 (HTLV-1 and HTLV-2), or syphilis (rapid plasma 24 reagin [RPR])
- •Have clinically significant and active bacterial, viral, fungal, or parasitic infection at screening
- •Have a white blood cell (WBC) count < 2 × 109/L
- •Have a left ventricular ejection fraction < 45%
- •Have a screening estimated glomerular filtration rate < 60 mL/min/1.73 m2
- •Have a diagnosis of a significant psychiatric disorder that could seriously impede the ability to participate in the study
- •For women of childbearing potential: are pregnant or breastfeeding or lack adequate contraception
- •Are unable to comply with the study procedures, as assessed by the investigator
研究组 & 干预措施
Autologous CD34+ Hematopoietic Stem Cells Mobilization and Apheresis
On Days 1-5, participants will receive a Granulocyte colony-stimulating factor (G-CSF), such as filgrastim, as an injection or by vein over about 5 minutes.
If the study doctor thinks it is needed, participants will also receive plerixafor as an injection under the skin on Day 5 (and 6, if you have 2 days of apheresis).
干预措施: Apheresis (Procedure)
Autologous CD34+ Hematopoietic Stem Cells Mobilization and Apheresis
On Days 1-5, participants will receive a Granulocyte colony-stimulating factor (G-CSF), such as filgrastim, as an injection or by vein over about 5 minutes.
If the study doctor thinks it is needed, participants will also receive plerixafor as an injection under the skin on Day 5 (and 6, if you have 2 days of apheresis).
干预措施: G-CSF (filgrastim or biosimilar) (Drug)
Autologous CD34+ Hematopoietic Stem Cells Mobilization and Apheresis
On Days 1-5, participants will receive a Granulocyte colony-stimulating factor (G-CSF), such as filgrastim, as an injection or by vein over about 5 minutes.
If the study doctor thinks it is needed, participants will also receive plerixafor as an injection under the skin on Day 5 (and 6, if you have 2 days of apheresis).
干预措施: Plerixafor (Drug)
结局指标
主要结局
Safety and adverse events (AEs)
时间窗: Through study completion; an average of 1 year.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
次要结局
未报告次要终点