Reduced Intensity Hematopoietic Cell Transplantation for Patients With Resistant Langerhans Cell Histiocytosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Disease-free Survival at 12 Months Post Transplantation
研究概览
简要总结
RATIONALE: Giving a monoclonal antibody, such as alemtuzumab, and chemotherapy drugs, such as fludarabine and melphalan, before a donor stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells and helps stop the growth of abnormal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving alemtuzumab together with fludarabine and melphalan followed by a donor stem cell transplant works in treating young patients with resistant Langerhans cell histiocytosis.
详细描述
OBJECTIVES:
Primary
- To determine the overall and disease-free survival of poor-risk pediatric patients with Langerhans cell histiocytosis at 1 and 3 years after reduced-intensity hematopoietic cell transplantation (RI-HCT).
Secondary
- To determine day 100 transplantation-related mortality.
- To determine the incidence of hematopoietic recovery and chimerism at day 100 and at 1 year post RI-HCT.
- To determine the incidence of grades II-IV and III-IV acute graft-versus-host disease (GVHD).
- To determine the incidence of chronic GVHD.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed Langerhans cell histiocytosis (LCH) by demonstration of CD1a positivity or Birbeck granules in lesions
- •Considered poor-risk, defined as multisystem disease with involvement of one or more risk organs (i.e., liver, spleen, lungs, and/or hematopoietic system)
- •No isolated "lung only" LCH
- •Progressive disease after one of the following treatments:
- •LCH-III protocol or other standard LCH-directed therapies
- •At least 1 course of the current salvage protocol (i.e., LCH-2 2005) or similar therapy (e.g., cytosine arabinoside or cladribine-based regimens)
- •HLA-matched related or unrelated donor OR unrelated umbilical cord blood (UCB) available
- •1 locus mismatch for donor allowed
- •Up to 2 loci mismatch for unrelated UCB allowed
- •Any hematologic status (transfusion support allowed)
- •Adequate hepatic, renal, cardiac, and pulmonary function to undergo reduced-intensity hematopoietic cell transplantation (RI-HCT) including the following:
- •Transaminases < 5 times upper limit of normal (ULN)
- •Bilirubin < 3 times ULN (unless secondary to hepatic LCH)
- •Creatinine ≤ 2 mg/dL (adults) (if creatinine > 1.2 OR history of renal dysfunction, must have estimated creatinine clearance > 40 mL/min)
- •Creatinine clearance > 40 mL/min (pediatrics)
- •Glomerular filtration rate ≥ 50mL/min
- •Negative pregnancy test
排除标准
- •Decompensated congestive heart failure, uncontrolled arrhythmia, or left ventricular ejection fraction ≥ 35%
- •Pulmonary failure (i.e., requiring mechanical ventilation) unless secondary to active underlying LCH
- •Isolated liver sclerosis or pulmonary fibrosis unless secondary to active underlying LCH
- •Uncontrolled active life-threatening infection
- •Pregnant or nursing
- •Less than 4 weeks after last attempted salvage chemotherapy treatment
- •Other concurrent chemotherapy agents (e.g., methotrexate) during entire transplantation period up to day 100 post-transplantation
研究组 & 干预措施
Alemtuzumab
Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.
干预措施: alemtuzumab (Biological)
Alemtuzumab
Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.
干预措施: fludarabine phosphate (Drug)
Alemtuzumab
Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.
干预措施: melphalan (Drug)
Alemtuzumab
Patients administered with alemtuzumab, fludarabine phosphate, melphalan and donor stem cell transplantation in children with resistant Langerhans cell histiocytosis.
干预措施: stem cell transplantation (Procedure)
结局指标
主要结局
Disease-free Survival at 12 Months Post Transplantation
时间窗: Year 1
This outcome is defined as survival with resolution of LCH at 12 months post transplant. Unresolved disease for over 12 months post-transplant, progressive disease after this time period, recurrence of disease and death from any cause are considered events. Those who survive with resolution of disease are censored at the date of last contact.
Overall Survival
时间窗: Year 1, Year 3
Count of patients alive at 1 and 3 years. Deaths from any cause are events. Surviving patients are censored at the date of last contact.
次要结局
- Transplantation-related Death(Day 100)
- Neutrophil Engraftment(Day 100)
- Incidence of Grade II-IV Acute Graft-versus-host-disease (GVHD)(Day 100 and Month 6)
- Incidence of Chronic GVHD(Day 100 and Month 6)
- Platelet Engraftment(Day 100)
- Incidence of Grade III-IV Acute Graft-versus-host-disease (GVHD)(Day 100 and Month 6)