HLA-Nonidentical Stem Cell and Natural Killer Cell Transplantation for Children Less the Two Years of Age With Hematologic Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- One-year Survival
研究概览
简要总结
Recent studies of conventional chemotherapy for infants with high-risk hematologic malignancies show that the long-term disease-free survival is low. Although blood and marrow stem cell transplantation using an HLA identical sibling has improved the outcome for these children, less than 25% have this donor source available. Another option is haploidentical transplantation using a partially matched family member donor (i.e. parental donor).
Although haploidentical transplantation has proven curative for some patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including infection and graft versus host disease (GVHD). Building on prior institutional trials, this study will provide patients a haploidentical graft depleted of T lymphocytes using the investigational device, CliniMACS selection system. One week after the transplant procedure, patients will also receive an infusion of additional donor derived white blood cells called Natural Killer (NK) cells in an effort to decrease risks for rejection of the graft, disease relapse, and regimen related toxicity. The primary objective of the study is to evaluate 1 year survival in infants with high risk hematologic malignancies who receive this study treatment.
详细描述
Secondary objectives for this study include the following:
- To estimate the incidence of three transplant-related adverse outcomes (i.e., regimen-related mortality, engraftment failure, and fatal acute GVHD) in the first 100 days after transplantation.
- To estimate the incidence of chronic graft-versus-host disease.
- To evaluate those factors that affect one-year survival.
- To assess the kinetics of lymphohematopoietic reconstitution.
- To assess the frequency and clinical relevance of minimal residual disease (MRD) before and after transplantation.
- To evaluate the incidence of and risk factors for long-term neurocognitive deficit and organ dysfunction.
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
- — 至 24 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have one of the following diagnosis:
- •AML in remission or relapse (e.g., FAB M7 or biphenotypic leukemia)
- •High-risk ALL in first remission (e.g., poor responder to prednisone, Ph+ ALL)
- •ALL beyond first remission
- •Secondary leukemia
- •Primary myelodysplasia (including RAEB, RAEB-T, CMML, JCML, and JMML)
- •Chronic myeloid leukemia
- •Histiocytoses (including multi-system Langerhans' cell histiocytosis and hemophagocytic lymphohistiocytosis
- •Inclusion criteria Donor research participants
- •HIV negative (date).
- •Hepatitis B surface antigen negative (date).
- •Hepatitis C antibody negative (date).
- •Syphilis negative (date).
- •Donor is equal to or greater than 3 on 6 HLA match (date).
- •Not pregnant (negative pregnancy test).
- •Not lactating.
- •At least 18 years of age.
- •Exclusion Criteria
- •Patients greater than 24 months of age at the time of transplant.
- •HLA-identical sibling donor is available.
- •Cardiac function: shortening fraction <25%.
- •Pulse oximetry oxygen saturation <92% on room air.
- •Glomerular filtration rate less than 40 ml/min/1.73 m2 (may use Technetium-99 result for GFR).
- •Direct bilirubin > 3 mg/dl.
- •SGPT > 500 U/L.
- •Patients with previous allergy to mouse proteins.
- •Patients with previous allergy to rabbit serum products.
- •Patients with Down's syndrome
排除标准
- 未提供
研究组 & 干预措施
Study Participants
Participants who meet the eligibility criteria for this study. Donor cells will be obtained using the Miltenyi Biotec CliniMACS device.
Interventions: Chemotherapy and antibodies, allogeneic stem cell transplantation.
干预措施: Chemotherapy and antibodies (Drug)
Study Participants
Participants who meet the eligibility criteria for this study. Donor cells will be obtained using the Miltenyi Biotec CliniMACS device.
Interventions: Chemotherapy and antibodies, allogeneic stem cell transplantation.
干预措施: Miltenyi Biotec CliniMACS (Device)
Study Participants
Participants who meet the eligibility criteria for this study. Donor cells will be obtained using the Miltenyi Biotec CliniMACS device.
Interventions: Chemotherapy and antibodies, allogeneic stem cell transplantation.
干预措施: Allogeneic stem cell transplantation (Procedure)
结局指标
主要结局
One-year Survival
时间窗: One year after transplant
The one-year survival of infants with high-risk hematologic malignancies who receive a haploidentical transplant procedure using a total body irradiation (TBI)-excluding conditioning regimen followed by an HLA-nonidentical family donor hematopoietic stem cell (HSC) graft depleted of T cells ex vivo using the CliniMACS CD34+ selection system, with a subsequent infusion of donor NK cells purified ex vivo using the CliniMACS CD3+ depletion and CD56+ enrichment system. The Kaplan-Meier estimate for one-year survival is reported.
次要结局
- Number of Incidences of Chronic GVHD.(Up to 5 years after transplant)
- Number of Transplant-Related Adverse Outcomes: Regimen-Related Mortality(100 days post-transplantation)
- Number of Transplant-Related Adverse Outcomes: Fatal Acute Graft-Versus Host Disease (GVHD)(100 days post-transplantation)
- Factors Affecting One-year Survival: Median Dose of CD34(Up to one year after transplant)
- Factors Affecting One-year Survival: Minimal Residual Disease (MRD)(Up to one year after transplant)
- Number of Transplant-Related Adverse Outcomes: Engraftment Failure(100 days post-transplantation)
- Frequency of and Clinical Relevance of Minimal Residual Disease (MRD) Before and After Transplantation(Baseline before HSCT, 1 year post HSCT, and up to 5 years post HSCT)
- Factors Affecting One-year Survival: Median Age of Donor at HSCT(Up to one year after transplant)
- Factors Affecting One-year Survival: Median Dose of NK Cells(Up to one year after transplant)
- Factors Affecting One-year Survival: Match N/6 HLA Loci(Up to one year after transplant)
- Kinetics of Lymphohematopoietic Reconstitution(From 0-3 months after HSCT through 4-5 years after HSCT)
- Factors Affecting One-year Survival: Donor Type(Up to one year after transplant)
- Incidence of and Risk Factors for Long-term Neurocognitive Deficit.(Up to 5 Years after transplant)
- Factors Affecting One-year Survival: Disease Status at HSCT(Up to one year after transplant)
- Incidence of and Risk Factors for Organ Dysfunction.(Up to 5 Years after transplant)