A Phase 1 Trial of a Single ProHema® CB Product as Part of Single Cord Blood Unit Transplant After Busulfan/Cyclophosphamide/ATG Conditioning for Pediatric Patients With Inherited Metabolic Disorders
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 4
- 主要终点
- Safety Profile, Assessed Primarily by Neutrophil Engraftment
研究概览
简要总结
The purpose of this study is to describe the safety profile of ProHema-CB as part of a single cord blood unit transplant after a myeloablative conditioning regimen in pediatric patients with inherited metabolic disorders. The safety profile will primarily be assessed by neutrophil engraftment.
详细描述
This study is an open-label trial of the safety of a single cord blood transplant using ProHema-CB following busulfan/cyclophosphamide/ATG conditioning for pediatric patients with inherited metabolic disorders.
A maximum of 12 eligible male and female subjects (1 to 18 years old, inclusive) will be enrolled and treated in the trial at approximately 1 to 3 centers within the U.S.
All subjects will be admitted to the hospital, per institutional practice and will receive a conditioning regimen, after which they will receive a HLA-matched or partially matched ProHema -CB unit on Day 0.
They will receive study follow up assessments weekly following Day 0 through Day 100 and study visit Days 180, 270, 365 and 730.
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 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have a confirmed diagnosis of an inherited metabolic disorder (IMD) and be amenable to treatment by hematopoietic cell transplantation:
- •Mucopolysaccharidoses: Hurler Syndrome (MPS IH), MPS I-HS (Hurler-Scheie Syndrome), Hunter Syndrome (MPS II), Sanfilippo Syndrome (MPS III), or MPS VI (Maroteaux-Lamy syndrome) with early neurologic involvement and/or sensitization to enzyme replacement therapy (ERT); or
- •Leukodystrophies: Krabbe disease (Globoid Leukodystrophy), Metachromatic Leukodystrophy (MLD), Adrenoleukodystrophy (ALD and AMN); or
- •Other IMD with lysosomal storage disorder including glycoproteinoses (Alpha-Mannosidosis, Mucolipidosis II or I-Cell disease), sphingo- and other lipidoses (Sandhoff disease, Tay Sachs disease, Pelizaeus Merzbacher (PMD), Niemann-Pick disease, GM1 gangliosidosis, Wolman's disease.
- •Male and female subjects aged 1 to 18 years, inclusive.
- •Lack of 4 6/6 HLA matched non-carrier related UCB or 8/8 HLA A, B, C, DRß1 matched non-carrier related or 8/8 unrelated bone marrow donor; or donor not available within appropriate timeframe, as determined by the transplant physician.
- •Availability of suitable primary and secondary umbilical cord blood (UCB) units.
- •Adequate performance status, defined as:
- •Subjects ≥ 16 years: Karnofsky score ≥ 70%.
- •Subjects < 16 years: Lansky score ≥ 70%.
- •Cardiac: Left ventricular ejection fraction at rest must be > 40%, or shortening fraction > 26%.
- •Subjects > 10 years: DLCO (diffusion capacity) > 50% of predicted (corrected for hemoglobin)
- •FEV1, FVC > 50% of predicted; Note: If unable to perform pulmonary tests, then O2 saturation > 92% on room air.
- •Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or GFR) > 70mL/min/1.73m
- •Hepatic: Bilirubin ≤ 2.5 mg/dL (except in the case of Gilbert's syndrome, ongoing hemolytic anemia, or due to the primary IMD); and ALT, AST and Alkaline Phosphatase ≤ x 3 ULN (all elevations beyond the ULN must be secondary to the primary IMD and not a comorbid condition).
- •Signed IRB approved Informed Consent Form (ICF).
排除标准
- •Evidence of HIV infection or HIV positive serology.
- •Current uncontrolled bacterial, viral or fungal infection (progression of clinical symptoms despite therapy).
- •Requirement for continuous respiratory supportive therapy (e.g. ventilator). Patients on intermittent respiratory support should be discussed with the Sponsor.
- •Active problems related to chronic aspiration.
- •Uncontrolled seizures.
- •Any active malignancy or myelodysplastic syndrome or any history of malignancy.
- •Inability to give informed consent/assent or to comply with the requirements for care after allogeneic stem cell transplantation.
- •Female subjects that are breastfeeding or with a positive pregnancy (HCG) test at Screening.
- •Use of an investigational drug within 30 days prior to screening for the primary IMD.
研究组 & 干预措施
ProHema-CB
ProHema-CB represents Ex Vivo Modulated Human Cord Blood Cells. Each subject will receive one administration of ProHema-CB unit transplant.
干预措施: ProHema-CB Transplant (Biological)
结局指标
主要结局
Safety Profile, Assessed Primarily by Neutrophil Engraftment
时间窗: Engraftment by Day 42 following study transplant procedure
次要结局
未报告次要终点