Allogeneic Hematopoietic Stem Cell Transplant for Patients With High Risk Hemoglobinopathy Using a Preparative Regimen to Achieve Stable Mixed Chimerism
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Number of Patients Who Experienced Grade 3-5 Treatment Related Toxicity
研究概览
简要总结
This study tests the clinical outcomes of one of two preparative regimens (determined by available donor source) in patients with non-malignant hemoglobinopathies. The researchers hypothesize that these regimens will have a positive effect on post transplant engraftment and the incidence of graft-versus-host-disease.
Regimen A2 has replaced Regimen A in this study. Two patients were treated on Regimen A but did not have evidence of initial engraftment thus triggering the stopping rule for that arm of this study.
详细描述
Prior to transplantation, subjects will receive either:
Cyclophosphamide, Fludarabine, Campath, Total body irradiation (TBI)
Or
Busulfan, Cyclophosphamide, antithymocyte globulin (ATG), granulocyte colony-stimulating factor (GSCF)
These drugs (and the radiation) are being given to help the new stem cells take and grow. On the day of transplantation, subjects will receive stem cells transfused via intravenous (IV) catheter.
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 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with Sickle Cell Disease/Thalassemia (SCD/THAL) 0-50 years of age with an acceptable stem cell donor and disease characteristic defined by the following:
- •Stroke, central nervous system (CNS) hemorrhage or a neurologic event lasting longer than 24 hours, or abnormal cerebral magnetic resonance imaging (MRI) or cerebral arteriogram or MRI angiographic study and impaired neuropsychological testing
- •Acute chest syndrome with a history of recurrent hospitalizations or exchange transfusions
- •Recurrent vaso-occlusive pain 3 or more episodes per year for 3 years or more years or recurrent priapism,
- •Impaired neuropsychological function and abnormal cerebral MRI scan
- •Stage I or II sickle lung disease,
- •Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration rate [GFR] 30-50% of the predicted normal value)
- •Bilateral proliferative retinopathy and major visual impairment in at least one eye
- •Osteonecrosis of multiple joints with documented destructive changes
- •Requirement for chronic transfusions but with red blood cell (RBC) alloimmunization >2 antibodies during long term transfusion therapy
- •Patients with transfusion dependent alpha- or beta-thalassemia 0-35 years of age with an acceptable stem cell donor as defined in the criteria in section above.
- •Patients with other non-malignant hematologic disorders that are transfusion-dependent or involve other potentially life-threatening cytopenias (including but not limited to Severe Congenital Neutropenia, Diamond-Blackfan Anemia and Shwachman-Diamond Syndrome) who are 0-35 years of age with an acceptable stem cell donor
- •Second Transplants
- •Patients with sickle cell disease or thalassemia who have failed to engraft or have autologous recovery after a myeloablative SCT regimen or non-myeloablative regimen are eligible for this protocol.
- •Regimen A2 will be utilized for patients with sickle cell disease or thalassemia who do not have an HLA-identical sibling donor or for any patient who has pre-existing organ dysfunction making them ineligible for a myeloablative preparative regimen.
- •Regimen B will be utilized for patients with sickle cell disease or thalassemia who have an HLA-identical sibling donor.
- •Patients must meet above criteria.
- •If the patient has received prior radiation therapy, eligibility to receive additional radiation therapy must be determined by Dr. Dusenbery
- •If first transplant was a non-myeloablative regimen, the second transplant can occur at any time
- •If the first transplant was a myeloablative regimen, then the second transplant must be > 6 months from the first transplant
排除标准
- •Patients with one or more of the following:
- •Karnofsky or Lansky performance score <70
- •Acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on biopsy
- •Stage III-IV lung disease
- •GFR<30% predicted
- •Pregnant or lactating females
- •Active serious infection whereby patient has been on intravenous antibiotics for one week prior to study entry. Any patient with AIDS or ARC or HIV seropositivity
- •Psychologically incapable of undergoing bone marrow transplant (BMT) with associated strict isolation or documented history of medical non-compliance
- •Patients not able to receive total lymphocytic irradiation (TLI) due to prior radiation therapy
研究组 & 干预措施
RIC Bu/Flu (A) (discontinued)
Full Preparative Regimen for subjects with matched donors using Busulfan on Day -8 and -7, Fludarabine on Day -6 through -2, antithymocyte globulin (ATG) on Day -2 through -1, total lymphoid radiation (TLI) on Day -1, stem cell infusion on Day 0.
干预措施: Busulfan, Fludarabine, ATG, TLI (Drug)
MA Bu/Cy (B)
Myeloablative Preparative Regimen for subjects with HLA identical sibling donors consists of Busulfan on day -9 through -6, Cyclophosphamide on day -5 through -2, ATG on day -3 through -1, stem cell infusion on Day 0 and Granulocyte Colony Stimulating Factor on day -3 until ANC >2500 x 2 days.
干预措施: Busulfan, Cyclophosphamide, ATG, GCSF (Drug)
MA Bu/Cy (B)
Myeloablative Preparative Regimen for subjects with HLA identical sibling donors consists of Busulfan on day -9 through -6, Cyclophosphamide on day -5 through -2, ATG on day -3 through -1, stem cell infusion on Day 0 and Granulocyte Colony Stimulating Factor on day -3 until ANC >2500 x 2 days.
干预措施: Total Body Irradiation (Radiation)
MA Bu/Cy (B)
Myeloablative Preparative Regimen for subjects with HLA identical sibling donors consists of Busulfan on day -9 through -6, Cyclophosphamide on day -5 through -2, ATG on day -3 through -1, stem cell infusion on Day 0 and Granulocyte Colony Stimulating Factor on day -3 until ANC >2500 x 2 days.
干预措施: Stem cell infusion (Procedure)
RIC Cy/Flu/TBI (A2)
Patients with sickle cell disease or thalassemia who do not have an HLA-identical sibling donor or who has pre-existing organ dysfunction making myeloablative condition ineligible will receive Campath on day -10 through -6, Cyclophosphamide on day -7, Fludarabine on day -6 through -2, total body irradiation (TBI) on day -1, stem cell infusion on Day 0.
干预措施: Campath, Fludarabine, Cyclophosphamide (Drug)
RIC Cy/Flu/TBI (A2)
Patients with sickle cell disease or thalassemia who do not have an HLA-identical sibling donor or who has pre-existing organ dysfunction making myeloablative condition ineligible will receive Campath on day -10 through -6, Cyclophosphamide on day -7, Fludarabine on day -6 through -2, total body irradiation (TBI) on day -1, stem cell infusion on Day 0.
干预措施: Total Body Irradiation (Radiation)
RIC Cy/Flu/TBI (A2)
Patients with sickle cell disease or thalassemia who do not have an HLA-identical sibling donor or who has pre-existing organ dysfunction making myeloablative condition ineligible will receive Campath on day -10 through -6, Cyclophosphamide on day -7, Fludarabine on day -6 through -2, total body irradiation (TBI) on day -1, stem cell infusion on Day 0.
干预措施: Stem cell infusion (Procedure)
结局指标
主要结局
Number of Patients Who Experienced Grade 3-5 Treatment Related Toxicity
时间窗: 1 year
In general, grade 3 equates to moderate, grade 4 to severe and grade 5 to death.
次要结局
- The Incidence of Chimerism at 6 Months(6 months)
- The Incidence of Grade 2-4 Acute Graft Versus Host Disease (Acute GVHD)(100 days)
- The Incidence of Grade 3-4 Acute Graft Versus Host Disease (Acute GVHD)(100 days)
- Change in the Patient's Quality of Life as Compared to the Pre-Transplant Assessment(2 years)
- The Incidence of Chimerism at 100 Days(100 days)
- Determine Physical Characteristics and Biologic Effects of Mixed Populations of Donor and Host Red Blood Cells(During study)
- Overall Survival(1 year)
- The Incidence of Chronic Graft Versus Host Disease (Chronic GVHD)(1 year)
- Determine the Concentration of Campath in the Serum(Day 0)
- The Incidence of Chimerism at 1 Year(1 year)
- Disease Free Survival(1 year)