NCT03128996招募中1 期
A Phase I/II Trial of Reduced Intensity Conditioning and Familial HLA-Mismatched Bone Marrow Transplantation in Children With Non-Malignant Disorders
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 29
- 试验地点
- 5
- 主要终点
- Donor engraftment
研究概览
简要总结
This study is designed to estimate the efficacy and toxicity of familial HLA mismatched bone marrow transplants in patients with non-malignant disease who are less than 21 years of age and could benefit from the procedure.
详细描述
Patients < 21 years of age with a non-malignant disorder benefited by hematopoietic stem cell transplant will receive a reduced intensity conditioning regimen consisting of hydroxyurea, alemtuzumab, fludarabine, thiotepa, and melphalan.
This will be followed by a familial HLA-mismatched bone marrow transplant. The primary objective is to establish safety and donor cell engraftment at 100 days and 1 year post-transplant.
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 Day 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •* Nonmalignant disorder requiring bone marrow transplant including bone marrow failure syndromes, metabolic disorders, immunologic disorders, or hemoglobinopathy
- •* For patients with sickle cell disease, must have one of the following severe manifestations:
- •1. Overt or silent stroke or persistently elevated transcranial doppler velocities despite transfusion therapy
- •2. Recurrent acute chest syndrome with significant respiratory compromise each time
- •3. Sickle nephropathy
- •4. Recurrent admissions for vaso-occlusive episodes resulting in prolonged opioid use and poor quality of life with interrupted school attendance activity
- •5. Red cell alloimmunization with the need for chronic transfusions
- •6. Recurrent osteonecrosis or multiple joint involvement from avascular necrosis
- •* Patients with sickle cell disease must have hemoglobin S \< 30% within 30 days prior to beginning alemtuzumab
- •* Age \/= 50
- •* Left ventricular ejection fraction \> 40% or left ventricular shortening fraction \> 26% by echocardiogram
- •* DLCO \> 40% (corrected for hemoglobin) or pulse oximetry with a baseline O2 saturation of \>/= 90% on room air if too young to perform PFTs
- •* Serum creatinine \ 70 mL/min/1.73m2
- •* Direct bilirubin \< 2x upper limit of normal for age
- •* ALT and AST \< 5x upper limit of normal for age
- •* Participants who have or are receiving \>/= 8 packed red blood cell transfusions for \>/= 1 year or \>/= 20 packed red blood cell transfusions (lifetime cumulative) will undergo liver MRI for estimation of hepatic iron content.
- •1\. Liver biopsy is indicated for hepatic iron content \>/= 7mg Fe/mg liver dry weight by liver MRI. Histologic examination of the liver must document for the absence of cirrhosis, bridging fibrosis, and active hepatitis
- •* Female subjects of childbearing potential, must agree to practice 2 methods of contraception at the same time from the time of signing of informed consent through 12 months post transplant. Male subjects must agree to practice effective barrier contraception or practice true abstinence from the time of signing informed consent through 12 months post transplant.
- •* Written informed consent must be obtained from all recipients in accordance with the guidelines of the institution's Human Studies Committee.
排除标准
- •Patients who have an HLA-identical sibling who is able and willing to donate bone marrow
- •Patients with cirrhosis or established bridging fibrosis of the liver or active hepatitis
- •Uncontrolled bacterial, viral, or fungal infection within 6 weeks prior to enrollment
- •Evidence of HIV infection or known HIV positive serology
- •Patients who have received a previous stem cell transplant
- •Patients who have received an investigational drug or device or off-label use of a drug or device within 3 months of enrollment
- •Females who are pregnant or breast feeding
- •Patients with active autoimmune disease (e.g. sarcoidosis, lupus, scleroderma)
研究组 & 干预措施
RIC Prep Regimen & GVHD Prophylaxis
Experimental
Single arm study. All patients receive the same Reduced Intensity Conditioning (RIC) regimen and GVHD prophylaxis regimen
干预措施: RIC regimen (Drug)
RIC Prep Regimen & GVHD Prophylaxis
Experimental
Single arm study. All patients receive the same Reduced Intensity Conditioning (RIC) regimen and GVHD prophylaxis regimen
干预措施: GVHD prophylaxis regimen (Drug)
结局指标
主要结局
Donor engraftment
时间窗: 100 days and 1 year post-transplant
as measured by chimerism
次要结局
- Time to neutrophil engraftment(100 days post-transplant)
- Time to platelet engraftment(100 days post-transplant)
- Effect of BMT on neurologic function(90 days, 1 year, and 2 years post-transplant)
- Effect of BMT on cardiac function(90 days, 1 year, and 2 years post-transplant)
- Incidence of acute graft-versus-host disease (GVHD)(1 year post-transplant)
- Pharmacokinetics of alemtuzumab(days -19, day 0, day +15, and day +30)
- Effect of BMT on pulmonary function(90 days, 1 year, and 2 years post-transplant)
- Effect of BMT on hepatic function(90 days, 180 days, 1 year, and 2 years post-transplant)
- Immune reconstitution(days +30, +60, +90, 1 year, 1.5 years, and 2 years post-transplant)
- Effect of BMT on renal function(90 days, 180 days, 1 year, and 2 years post-transplant)
- Pharmacokinetics of abatacept(days +30, +60, +90, 1 year, 1.5 years, and 2 years post-transplant)
- Incidence of chronic graft-versus-host disease (GVHD)(2 years post-transplant)
研究者
研究点 (5)
Loading locations...
相似试验
已完成
1 期
Safety Study of HLA-haplo Matched Allogenic Bone Marrow Derived Stem Cell Treatment in Amyotrophic Lateral SclerosisAmyotrophic Lateral SclerosisNeuromuscular DiseaseNeurodegenerative DiseaseCentral Nervous System DiseaseMotor Neuron DiseaseNCT01758510Hanyang University Seoul Hospital6
招募中
2 期
Reduced Intensity Haploidentical BMT for High Risk Solid TumorsRefractory and/or Relapsed Metastatic Solid TumorsNCT01804634Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins60
已完成
早期 1 期
Combination Chemotherapy, Total Body Irradiation, and Donor Blood Stem Cell Transplant in Treating Patients With Primary or Secondary MyelofibrosisPrimary MyelofibrosisSecondary MyelofibrosisNCT03426969M.D. Anderson Cancer Center3
进行中（未招募）
1 期
Combination Chemotherapy, Total Body Irradiation, and Donor Blood Stem Cell Transplant in Treating Patients With Secondary MyelofibrosisSecondary MyelofibrosisNCT03118492City of Hope Medical Center22
撤回
2 期
Low-Dose Conditioning Followed by Donor Stem Cell Transplant in Treating Patients With Severe Systemic SclerosisSystemic SclerodermaNCT01047072Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium