A Pilot Study of Unrelated Umbilical Cord Blood Transplantation in Patients With High Risk Hematologic Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- rates of durable engraftment in patients
研究概览
简要总结
RATIONALE: Umbilical cord blood transplantation may allow doctors to give higher doses of chemotherapy or radiation therapy and kill more cancer cells.
PURPOSE: This phase II trial is studying allogeneic umbilical cord blood transplantation to see how well it works when given with chemotherapy or radiation therapy in treating patients with high-risk hematologic cancer.
详细描述
OBJECTIVES:
- Determine the rates of hematologic and immune reconstitution in patients with high risk hematologic malignancies who are undergoing high dose chemoradiotherapy followed by unrelated umbilical cord blood (UCB) transplantation.
- Determine the incidence of graft-versus-host-disease in this setting.
- Describe the incidence of recurrent disease in these patients post UCB transplant.
- Describe the incidence of serious infections and secondary lymphoproliferative diseases following transplantation with UCB in these patients.
- Determine specifically whether larger recipients can be durably engrafted with unrelated UCB, and determine whether nucleated cell or progenitor cell content of the graft is predictive of hematological engraftment.
OUTLINE: Patients may undergo a back-up peripheral blood stem cell collection prior to treatment.
Patients receive 9 fractions of total body irradiation (TBI) on days -9 to -5 followed by melphalan IV for three days on days -4 to -2 and antithymocyte globulin IV or methylprednisolone IV for three days on days -3 to -1. On day 0, patients receive umbilical cord blood infusion. If TBI is not tolerated, busulfan is substituted and administered orally every 6 hours for 4 days on days -8 to -5. Cyclosporine and methylprednisolone begin on day -2 and continue for 6 months.
Patients are followed at least monthly for 1 year, then every 6 months for the second year, and then annually thereafter.
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 54 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed high risk malignancy including:
- •Acute nonlymphocytic leukemia (ANLL) after induction failure, or in first complete remission with high risk features including stem cell or biphenotypic classification (acute myeloid leukemia (AML) M0), erythroleukemia (AML M6), acute megakaryocytic leukemia (AML M7), cytogenic markers indicative of poor prognosis, or failure to achieve complete remission after standard induction therapy
- •Acute lymphocytic leukemia (ALL) or ANLL in second or subsequent remission
- •Chronic myeloid leukemia (CML) in chronic phase
- •CML with accelerated phase or blast crisis are eligible after reinduction chemotherapy converts disease to chronic phase
- •High risk ALL in first complete remission
- •Myelodysplastic syndrome with evidence of evolution to acute myeloid leukemia
- •Refractory anemia with excess blasts
- •Refractory anemia with excess blasts in transformation
- •Non-Hodgkin's lymphoma (NHL), ANLL, or ALL with recurrent disease after autologous stem cell transplantation
- •Must also meet all the following conditions:
- •No HLA-ABC/DR identical related bone marrow or UCB donor
- •No 5/6 antigen matched related bone marrow or UCB donor
- •Condition precludes waiting to search and find a donor in the National Marrow Donor Registry
- •Must have an available serologic matched umbilical cord blood unit in the New York Blood Center's Placental Blood Project
- •No active CNS disease
- •PATIENT CHARACTERISTICS:
- •Under 55 at time of umbilical cord blood transplantation
- •Performance status:
- •Zubrod 0-1
- •Karnofsky 80-100%
- •Life expectancy:
- •At least 3 months
- •Hematopoietic:
- •For patients with ALL or ANLL in remission, CML in chronic phase, or NHL without marrow involvement who elect to undergo autologous peripheral blood stem cell collection and storage:
- •WBC at least 3,000/mm^3
- •Absolute neutrophil count at least 1,000/mm^3
- •Platelet count at least 100,000/mm^3
- •Bilirubin no greater than 2.0 mg/dL
- •ALT/AST no greater than 4 times normal
- •Creatinine no greater than 2.0 mg/dL
- •Creatinine clearance at least 50 mL/min
- •Cardiovascular:
- •Normal cardiac function by echocardiogram or radionuclide scan (shortening fraction or ejection fraction at least 80% of normal value for age)
- •FVC and FEV_1 at least 60% of predicted for age
- •For adults:
- •DLCO at least 60% of predicted
- •HIV negative
- •No active infections at time of autologous stem cell harvest or pretransplant cytoreduction
- •Not pregnant or nursing
- •Effective contraception required of all fertile patients
- •PRIOR CONCURRENT THERAPY:
- •Biologic therapy:
- •Prior autologous stem cell transplantation allowed
- •Chemotherapy:
- •See Disease Characteristics
- •Endocrine therapy:
- •Not specified
- •Radiotherapy:
- 另有 2 项未显示
排除标准
- 未提供
结局指标
主要结局
rates of durable engraftment in patients
时间窗: day 42
The primary study end point will be hematologic engraftment. Engraftment is defined as achieving ANC larger than or equal to 500 ul/mm3 of donor origin for three consecutive measurements on different days by day +42.
次要结局
- Event-free survival by clinical and pathological disease assessment(at disease progression or death)
- incidence of recurrent disease in patients post UCB transplant(post transplant)