NCT00392782终止2 期
A Multicenter, Prospective Trial to Evaluate the Role of NK Cell KIR Epitope Mismatch on Mortality and Disease Relapse in T-Cell Depleted Hematopoietic Stem Cell Transplantation From HLA-C Mismatched, Unrelated Donors for Myeloid Malignancies
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 9
- 主要终点
- Incidence of Disease-free Survival
研究概览
简要总结
RATIONALE: Giving total-body irradiation and chemotherapy, such as fludarabine and thiotepa, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When 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 antithymocyte globulin and removing the T cells from the donor cells before transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well a donor stem cell transplant works in treating patients with myeloid cancer or other disease.
详细描述
OBJECTIVES:
Primary
- Determine the incidence of disease-free survival at 1 year in patients with acute or chronic myeloid leukemias undergoing T-cell-depleted hematopoietic stem cell transplantation from HLA-C mismatched, unrelated donors.
Secondary
- Determine the incidence of disease relapse at 1 year in patients treated with this regimen.
- Determine the incidence and severity of acute graft-vs-host disease (GVHD) at 100 days and chronic GVHD at 1 year in these patients.
- Determine the incidence of graft failure at day 100.
- Determine the transplant-related mortality of these patients at 1 year.
- Determine the overall survival of these patients at 1 year.
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 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Primary acute myeloid leukemia (AML)
- •First complete remission (CR) with high risk features as defined by: failure to achieve remission by day 21 after induction chemotherapy, or the presence of chromosomal abnormalities involving any of the following: -5/de (5q), -7/del(7q), inversion 3q, abnormalities of 11q23, 20q, 21q, del(9q), translocation 6;9, translocation 9;22, abnormalities of 17p, or complex karyotype with > or = 3 abnormalities. Complete remission is defined as < 5% blasts in the marrow.
- •Second CR or subsequent in remission
- •Refractory or relapsed disease with absolute peripheral blood blasts < 2000/mcL
- •Secondary AML in remission or relapse
- •Chronic myelogenous leukemia (CML) in accelerated or blast phase
- •Accelerated phase is defined by any one of the following:
- •Blasts 10% to 19% of peripheral blood white cells or bone marrow cells
- •Peripheral blood basophils at least 20%
- •Persistent thrombocytopenia (<100 x 10^9/L) unrelated to therapy, or persistent thrombocytosis (>1000 x 10^9/L) unresponsive to therapy
- •Increasing spleen size and increasing white blood cell (WBC) count unresponsive to therapy
- •Cytogenetic evidence of clonal evolution (i.e., the appearance of an additional genetic abnormality that was not present in the initial specimen at the time of diagnosis of chronic phase CML)
- •Resistance to tyrosine kinase inhibitors (imatinib or other) defined as no complete cytogenetic response even if the above criteria are not met.
- •Blast phase is defined by either of the following:
- •Blasts 20% or more of peripheral blood white cells or bone marrow cells
- •Extramedullary blast proliferation
- •Large foci or clusters of blasts in bone marrow biopsy
- •Primary myelodysplastic syndrome (MDS) with an IPSS score >1
- •Secondary MDS with any international prostate symptom score (IPSS)
- •Age ≤60 years
- •Co-Morbidity score 0-2
- •At least 35 days following start of preceding leukemia induction therapy
排除标准
- •Patients for whom a suitable HLA genotypically identical sibling or fully matched HLA-A, -B, -C, and -DRB1 unrelated donor is available.
- •Patients greater than 60 years of age.
- •Hypersensitivity to thymoglobulin.
- •Symptomatic uncontrolled coronary artery disease or congestive heart failure.
- •Hepatic disease with transaminases or bilirubin > 2 times upper limit of normal (ULN) except for isolated hyperbilirubinemia attributed to Gilbert's syndrome.
- •Severe hypoxemia with room air - Partial Pressure of Oxygen in Arterial Blood - (PAO2) < 70, supplemental oxygen-dependence, or carbon monoxide diffusing capacity (DLCO) < 50% predicted.
- •Impaired renal function with creatinine > 2 times upper limit of normal (ULN) or creatinine clearance measured by 24-hour urine collection < 50% normal for age, gender, and weight.
- •Patients with central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy.
- •Patients who are human immunodeficiency virus (HIV) seropositive.
- •Patients who are pregnant or breast-feeding.
- •Patients with active infections that are untreated, or failing to respond to appropriate therapy.
- •Karnofsky performance status < 50%.
- •Prior allogeneic or autologous bone marrow, peripheral blood stem cell, or umbilical cord blood transplant.
- •Inability to provide informed consent.
- •Co-morbidity score >2
- •Less than 35 days from start of previous leukemia induction therapy
研究组 & 干预措施
Natural Killer Cell Kir Epitope
Experimental
干预措施: anti-thymocyte globulin (Biological)
Natural Killer Cell Kir Epitope
Experimental
干预措施: fludarabine phosphate (Drug)
Natural Killer Cell Kir Epitope
Experimental
干预措施: thiotepa (Drug)
Natural Killer Cell Kir Epitope
Experimental
干预措施: peripheral blood stem cell transplantation (Procedure)
Natural Killer Cell Kir Epitope
Experimental
干预措施: total-body irradiation (Radiation)
结局指标
主要结局
Incidence of Disease-free Survival
时间窗: 1 Year
Number of patients alive and without disease at 1 year after transplant.
次要结局
- Incidence of Disease Relapse(1 Year)
- Incidence of Graft Failure(Day 100)
- Incidence of Grade II-IV Acute Graft-vs-host Disease (GVHD)(Day 100)
- Incidence of Chronic Graft-versus-host Disease (GVHD)(1 Year)
- Transplant-related Mortality(1 Year)
- Overall Survival(1 Year)
研究者
研究点 (9)
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