Unrelated Donor Transplant Versus Immune Therapy in Pediatric Severe Aplastic Anemia
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 13
- 主要终点
- Percentage of patients randomized to HSCT that actually complete HSCT
研究概览
简要总结
The purpose of this study is to determine the feasibility of comparing outcomes of patients treated de novo with immunosuppressive therapy (IST) versus matched unrelated donor (MUD) hematopoietic stem cell transplant (HSCT) for pediatric acquired severe aplastic anemia.
详细描述
A major challenge in treating pediatric Severe Aplastic Anemia (SAA) is the determination of best primary therapy for patients who lack a fully matched related donor for HSCT. Good survival outcomes have been seen with IST, but initial and late failures, CSA dependence, persistent cytopenias and secondary Myelodysplastic Syndrome (MDS) / Acute Myeloid Leukemia (AML) in a portion of patients leave considerable room for improvement. MUD HSCT survival in SAA has markedly improved, but a direct comparison of this approach with IST is necessary to determine whether this approach is feasible and will lead to better Event Free Survival. This trial will address the feasibility of randomization, test whether patients can be evaluated in a timely fashion and safely begin therapy with MUD HSCT or IST, and give a preliminary assessment of the safety of up-front MUD HSCT. If successful, this trial will lead to a future prospective trial comparing directly IST to MUD HSCT in this disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- — 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of idiopathic SAA, defined as:
- •Bone marrow cellularity <25%, or <30% hematopoietic cells.
- •Two out of three of the following (in peripheral blood): neutrophils <0.5 x109/L, platelets <20 x109/L, reticulocyte count <60 x109/L with hemoglobin <8g/dL.
- •Age ≤25 years old.
- •No suitable fully matched related donor available (minimum 6/6 match for Human Leukocyte antigen (HLA) -A and B at intermediate or high resolution and DRB1 at high resolution using DNA based typing).
- •At least two unrelated donors noted on National Marrow Donor Program (NMDP) search who are well matched (9/10 or 10/10 for HLA-A, B, C, DRB1, and DQB1 using high resolution).
- •Signed informed consent for the randomized trial by patient and/or legal guardian.
- •Adequate organ function defined as in the judgment of the investigator, there is not irreversible organ damage that would preclude the patient from meeting the organ function inclusion criteria for HSCT listed in section 2.3.4 by the intended time of HSCT (6-8 weeks after randomization) or preclude patients from receiving horse ATG.
排除标准
- •Inherited bone marrow failure syndromes (IBMFS). The diagnosis of Fanconi anemia must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow. Telomere length testing should be sent on all patients to exclude Dyskeratosis congenita, but if results are delayed or unavailable and there are no clinical manifestations of DC, patients may enroll. If patients have clinical characteristics suspicious for Shwachman Diamond syndrome, this syndrome must be excluded by pancreatic isoamylase testing or gene mutation analysis. Note: pancreatic isoamylase testing is not accurate in children less than 3 years.
- •Clonal cytogenetic abnormalities or fluorescence In Situ Hybridization (FISH) pattern consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on marrow examination (see section 4.2.3.1 for details of the required MDS FISH panel).
- •Known severe allergy to horse ATG.
- •Prior allogeneic stem cell transplant.
- •Prior solid organ transplant.
- •Infection with human immunodeficiency virus (HIV).
- •Active Hepatitis B or C. This should be excluded in patients where there is clinical suspicion of hepatitis (e.g. elevated LFTs).
- •Female patients who are pregnant or breast-feeding.
- •Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ.
研究组 & 干预措施
Immunosuppressive Therapy
Patient will receive standard immunosuppressive therapy combination of drugs: horse anti-thymocyte globulin (ATG) and cyclosporine.
干预措施: cyclosporine (Drug)
Immunosuppressive Therapy
Patient will receive standard immunosuppressive therapy combination of drugs: horse anti-thymocyte globulin (ATG) and cyclosporine.
干预措施: horse anti-thymocyte globulin (ATG) (Drug)
Immunosuppressive Therapy
Patient will receive standard immunosuppressive therapy combination of drugs: horse anti-thymocyte globulin (ATG) and cyclosporine.
干预措施: Immunosuppressive Therapy (IST) (Procedure)
Matched Unrelated Stem Cell Transplant
Patient will under go matched unrelated donor transplant of hematopoietic stem cells as their therapy using fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin (ATG), and low-dose total body irradiation (TBI) as preparative regimen and cyclosporine and methotrexate for graft versus host disease (GVHD) prevention.
干预措施: cyclosporine (Drug)
Matched Unrelated Stem Cell Transplant
Patient will under go matched unrelated donor transplant of hematopoietic stem cells as their therapy using fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin (ATG), and low-dose total body irradiation (TBI) as preparative regimen and cyclosporine and methotrexate for graft versus host disease (GVHD) prevention.
干预措施: Matched Unrelated Donor Hematopoietic Stem Cell Transplant (Procedure)
Matched Unrelated Stem Cell Transplant
Patient will under go matched unrelated donor transplant of hematopoietic stem cells as their therapy using fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin (ATG), and low-dose total body irradiation (TBI) as preparative regimen and cyclosporine and methotrexate for graft versus host disease (GVHD) prevention.
干预措施: rabbit anti-thymocyte globulin (ATG) (Drug)
Matched Unrelated Stem Cell Transplant
Patient will under go matched unrelated donor transplant of hematopoietic stem cells as their therapy using fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin (ATG), and low-dose total body irradiation (TBI) as preparative regimen and cyclosporine and methotrexate for graft versus host disease (GVHD) prevention.
干预措施: methotrexate (Drug)
Matched Unrelated Stem Cell Transplant
Patient will under go matched unrelated donor transplant of hematopoietic stem cells as their therapy using fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin (ATG), and low-dose total body irradiation (TBI) as preparative regimen and cyclosporine and methotrexate for graft versus host disease (GVHD) prevention.
干预措施: fludarabine (Drug)
Matched Unrelated Stem Cell Transplant
Patient will under go matched unrelated donor transplant of hematopoietic stem cells as their therapy using fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin (ATG), and low-dose total body irradiation (TBI) as preparative regimen and cyclosporine and methotrexate for graft versus host disease (GVHD) prevention.
干预措施: cyclophosphamide (Drug)
Matched Unrelated Stem Cell Transplant
Patient will under go matched unrelated donor transplant of hematopoietic stem cells as their therapy using fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin (ATG), and low-dose total body irradiation (TBI) as preparative regimen and cyclosporine and methotrexate for graft versus host disease (GVHD) prevention.
干预措施: low-dose total body irradiation (TBI) (Radiation)
结局指标
主要结局
Percentage of patients randomized to HSCT that actually complete HSCT
时间窗: 4 years
Feasibility of comparing outcomes of patients treated de novo with IST versus matched unrelated donor HSCT for pediatric acquired severe aplastic anemia as defined by percentage of patients randomized to HSCT that actually complete HSCT.
次要结局
- Treatment-related mortality at one year from randomization in both arms(1 Year)
- Time from screening consent to randomization(4 years)
- Overall Survival at one year from randomization in both arms(1 Year)
- Rates of secondary MDS or AML in both treatment arms.(4 years)
- Number of patients that fail to receive their primary assigned therapy (HSCT or IST).(4 years)
- Time from randomization to red blood cell recovery in both arms(4 years)
- Rates of grade II-IV and III-IV acute GVHD, and extensive chronic GVHD in the MUD HSCT arm(4 years)
- Rates of IST relapse(4 years)
- Rates of other secondary malignancies in both treatment arms.(4 years)
- Reasons why patients fail to receive their primary assigned therapy (HSCT or IST).(4 years)
- Time from randomization to neutrophil recovery in both arms(4 years)
- Time from randomization to cessation of immune suppression recovery in both arms(4 years)
- Rates of IST response(4 years)
- Development of symptomatic PNH in both treatment arms.(4 years)
- Time from randomization to platelet recovery in both arms(4 years)
- Rates of primary and secondary graft rejection in the MUD HSCT arm(4 years)
- Incidence of significant infection in both treatment arms(4 years)
- Time to immune reconstitution in the HSCT arm(4 years)
研究者
Michael Pulsipher
Principal Investigator
Pediatric Transplantation & Cellular Therapy Consortium