A Phase I Study to Examine the Toxicity of Allogeneneic Stem Cell Transplantation for Relapsed or Therapy Refractory Ewings
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Toxicity assessed by safety labs and close monitoring from the study staff
研究概览
简要总结
The purpose of this study is to examine the toxicity of using allogeneic stem cell transplantation for treatment of subjects with relapsed or refractory ES and rhabdomyosarcoma. This is a nanrandomized two-arm study is designed to determine the safety and incidence of graft versus host disease (GVHD) in patients with relapsed, refractory Ewings sarcoma receiving related and unrelated, allogeneic stem cell transplants.
详细描述
This study will examine the toxicity of using allogeneic stem cell transplantation for treatment of subjects with relapsed or refractory ES and rhabdomyosarcoma. Donors will consist of either HLA identical or 9/10 (A, B, C, DR, DQ) matched related or unrelated donors. Specifically, we will examine the toxicity of allogeneic stem cell transplant (SCT) in this patient population, as related to incidence of grade 3-4 acute GVHD and the incidence of transplant related mortality at 100 days by using the following treatment plans.
Rabbit anti-thymocyte globulin (ATG; thymoglobulin) will be given only to unrelated donor transplant recipients at a dose of 3 mg/kg/day I.V. for 3 consecutive days (Days -8 to-6). Equine ATG at a dose of 30mg/kg/day may be substituted in the event of severe allergic reaction to the rabbit ATG.
Busulfan (BU) will be given at a dose of 0.8 mg/kg IV q 6 hours, for 16 doses on days -8 through -5. Busulfan doses will be modified based upon pharmacokinetics data to maintain steady state levels of 600-900 ng/dl. Patients should start seizure prophylaxis with levetiracetam prior to the first dose of busulfan and discontinued 24 hours after the last dose of busulfan.
Melphalan will be given at a dose of 60 mg/m2 I.V. over 15-20 min on days -4 through -2 as per Pediatric SCT Standards of Practice Manual.
Fludarabine will be given at a dose of 30 mg/m2/day IV over 30 minutes for 5 doses on days -8 through -4.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 0-30 years with relapsed or therapy refractory ES, excluding patients with brain metastases. Patients who have received a prior autologous stem cell transplant are eligible.
- •Related and unrelated marrow and peripheral blood stem donors must be 9/10 or 10/10 (HLA A, B, C, DR, DQ) matched with the recipient
排除标准
- •Organ dysfunction: Patients who have the following levels of organ system dysfunction are not eligible:
- •Cardiac: Ejection Fraction < 50 %
- •Renal: Est. Creatinine Clearance < 50*
- •Hepatic: Bilirubin > 3.0
- •Pulmonary: DLCO < 70 %, or for patient who cannot cooperate with pulmonary function testing, O2 saturation < 95 % on room air.
- •Performance status: Lansky performance < 70; ECOG status > 2 *this is based on the Schwartz formula for children less than 18 years of age, and the Cockcroft - Gault formula, for those > 18 years.[21, 22]
- •Patients with an isolated local recurrence of their tumor (in the site of the primary tumor) > 1 year after completing therapy are excluded, as these patients could be cured with local therapy alone.
- •3 As a part of the standard of care for pre-transplant evaluation, subjects will be tested for exposure to viral agents such as hepatitis B, C, HTLV-1/2, and HIV. Subjects testing positive for HIV may be rejected as candidates for transplantation, based on the clinical judgment of the stem cell transplant physician
研究组 & 干预措施
Treatment Plan A
Rabbit anti-thymocyte globulin (ATG) will be given only to unrelated donor transplant recipients at a dose of 3 mg/kg/day I.V. Equine ATG at a dose of 30mg/kg/day may be substituted in the event of severe allergic reaction to the rabbit ATG. Rabbit ATG is only used with recipients of unrelated donor marrow or peripheral blood transplants. Busulfan (BU) will be given at a dose of 0.8 mg/kg IV q 6 hrs. BU doses will be modified based upon pharmacokinetics data to maintain steady state levels of 600-900 ng/dl. Seizure prophylaxis with levetiracetam should begin prior to the 1st dose of BU and stoped 24 hrs after the last dose of BU. Melphalan will be given at a dose of 60 mg/m2 I.V. over 15-20 min per Pediatric SCT Standards of Practice Manual.
干预措施: Rabbit anti-thymocyte globulin (Drug)
Treatment Plan A
Rabbit anti-thymocyte globulin (ATG) will be given only to unrelated donor transplant recipients at a dose of 3 mg/kg/day I.V. Equine ATG at a dose of 30mg/kg/day may be substituted in the event of severe allergic reaction to the rabbit ATG. Rabbit ATG is only used with recipients of unrelated donor marrow or peripheral blood transplants. Busulfan (BU) will be given at a dose of 0.8 mg/kg IV q 6 hrs. BU doses will be modified based upon pharmacokinetics data to maintain steady state levels of 600-900 ng/dl. Seizure prophylaxis with levetiracetam should begin prior to the 1st dose of BU and stoped 24 hrs after the last dose of BU. Melphalan will be given at a dose of 60 mg/m2 I.V. over 15-20 min per Pediatric SCT Standards of Practice Manual.
干预措施: Busulfan (Drug)
Treatment Plan A
Rabbit anti-thymocyte globulin (ATG) will be given only to unrelated donor transplant recipients at a dose of 3 mg/kg/day I.V. Equine ATG at a dose of 30mg/kg/day may be substituted in the event of severe allergic reaction to the rabbit ATG. Rabbit ATG is only used with recipients of unrelated donor marrow or peripheral blood transplants. Busulfan (BU) will be given at a dose of 0.8 mg/kg IV q 6 hrs. BU doses will be modified based upon pharmacokinetics data to maintain steady state levels of 600-900 ng/dl. Seizure prophylaxis with levetiracetam should begin prior to the 1st dose of BU and stoped 24 hrs after the last dose of BU. Melphalan will be given at a dose of 60 mg/m2 I.V. over 15-20 min per Pediatric SCT Standards of Practice Manual.
干预措施: Melphalan (Drug)
Treatment Plan B
Rabbit anti-thymocyte globulin (ATG) will be given only to unrelated donor transplant recipients at a dose of 3 mg/kg/day I.V. Equine ATG at a dose of 30mg/kg/day may be substituted in the event of severe allergic reaction to the rabbit ATG. Rabbit ATG is only used with recipients of unrelated donor marrow or peripheral blood transplants. Fludarabine will be given at a dose of 30 mg/m2/day IV over 30 mins for 5 doses. Cyclophosphamide will be given at a dose of 50 mg/kg/day IV over 2 hrs for 4 doses.
干预措施: Rabbit anti-thymocyte globulin (Drug)
Treatment Plan B
Rabbit anti-thymocyte globulin (ATG) will be given only to unrelated donor transplant recipients at a dose of 3 mg/kg/day I.V. Equine ATG at a dose of 30mg/kg/day may be substituted in the event of severe allergic reaction to the rabbit ATG. Rabbit ATG is only used with recipients of unrelated donor marrow or peripheral blood transplants. Fludarabine will be given at a dose of 30 mg/m2/day IV over 30 mins for 5 doses. Cyclophosphamide will be given at a dose of 50 mg/kg/day IV over 2 hrs for 4 doses.
干预措施: Fludarabine (Drug)
Treatment Plan B
Rabbit anti-thymocyte globulin (ATG) will be given only to unrelated donor transplant recipients at a dose of 3 mg/kg/day I.V. Equine ATG at a dose of 30mg/kg/day may be substituted in the event of severe allergic reaction to the rabbit ATG. Rabbit ATG is only used with recipients of unrelated donor marrow or peripheral blood transplants. Fludarabine will be given at a dose of 30 mg/m2/day IV over 30 mins for 5 doses. Cyclophosphamide will be given at a dose of 50 mg/kg/day IV over 2 hrs for 4 doses.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Toxicity assessed by safety labs and close monitoring from the study staff
时间窗: Over 5 Years
This will be assessed by safety labs and close monitoring from the study staff.
次要结局
未报告次要终点