Transplantation of Unrelated Umbilical Cord Blood for Patients With Hematological Diseases With Cyclophosphamide/Fludarabine/Total Body Irradiation Myeloablative Preparative Regimen
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 213
- 试验地点
- 2
- 主要终点
- Number of Participants Who Were Alive at 1 Year Transplant Overall Survival
研究概览
简要总结
RATIONALE: Giving chemotherapy drugs, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells and prepares the patient's bone marrow for the stem cells. When the 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 cyclosporine and mycophenolate mofetil may stop this from happening.
PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation works in treating patients who are undergoing an umbilical cord blood transplant for hematologic cancer.
详细描述
OBJECTIVES:
Primary
- Determine the 1-year survival of patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine, cyclophosphamide, and fractionated total-body irradiation.
Secondary
- Determine the incidence of transplant-related mortality at 6 months after UCBT.
- Evaluate the pattern of chimerism after double UCBT.
- Determine the incidence of neutrophil engraftment at day 42 after UCBT.
- Determine the incidence of platelet engraftment at 6 months after UCBT.
- Determine the incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at day 100 after UCBT.
- Determine the incidence of chronic GVHD at 1 year after UCBT.
- Determine the disease-free survival at 1 and 2 years after UCBT.
- Determine the incidence of relapse at 1 year after UCBT.
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 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Acute myeloid leukemia (AML): high risk CR1 (as evidenced by preceding myelodysplastic syndrome [MDS], high risk cytogenetics, ≥ 2 cycles to obtain complete remission [CR], erythroblastic or megakaryocytic leukemia; CR2+. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
- •Very high risk pediatric patients with AML. Patients <21 years, however, are eligible with (M2 marrow) with < or = 25% blasts in marrow after having failed one or more cycles of chemotherapy. This group of patients will be analyzed separately.
- •Acute lymphocytic leukemia (ALL): high risk CR1 [t(9;22), t (1:19), t(4;11) or other MLL rearrangements] hypodiploidy, or IKZF1 abnormalities), DNA index < 0.81, > 1 cycle to obtain CR or presence minimal residual disease (MRD). Patients in CR2+ are eligible. All patients must be in CR as defined by hematological recovery, AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
- •Very high risk pediatric patients with ALL. patients <21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction. They are eligible once they achieved a complete remission
- •Chronic myelogenous leukemia (CML) excluding refractory blast crisis. To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate.
- •Plasma Cell leukemia after initial therapy, who achieved at least a partial remission
- •Advanced myelofibrosis
- •Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt) or refractory anemia with severe pancytopenia or high risk cytogenetics. Blasts must be < 10% by a representative bone marrow aspirate morphology.
- •Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma or follicular lymphoma are eligible if there was disease progression/relapse within 12 of achieving a partial or complete remission. Patients who had remissions lasting > 12 months, are eligible after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm) should be considered for debulking chemotherapy before transplant.
- •Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy in CR1+ or PR1+.
- •Large cell NHL > CR2/> PR
- •Patients in CR2/PR2 with initial short remission (<6 months) are eligible.
- •Lymphoblastic lymphoma, Burkitt's lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1 year.
- •Multiple myeloma beyond PR
- •Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or β-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy.
- •Recipients must have a Karnofsky score (adults) ≥ 80 % or Lansky score ≥ 50% (pediatrics), and proper organ function.
- •Exclusion Criteria
- •Active infection at time of transplantation
- •History of human immunodeficiency virus (HIV) infection
- •Pregnant or breast feeding.
- •Chemotherapy refractory large cell and high grade NHL
- •If < or = 18 years old, prior myeloablative transplant within the last 6 months. If >18 years old prior myeloablative allotransplant or autologous transplant
- •Extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation.
- •Patients who have received Y-90 ibritumomab (Zevalin) or I-131 tostumomab (Bexxar), as part of their salvage therapy.
排除标准
- 未提供
研究组 & 干预措施
Unrelated UCBT for Blood Cancers
Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
干预措施: filgrastim (Biological)
Unrelated UCBT for Blood Cancers
Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
干预措施: cyclophosphamide (Drug)
Unrelated UCBT for Blood Cancers
Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
干预措施: cyclosporine (Drug)
Unrelated UCBT for Blood Cancers
Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
干预措施: fludarabine phosphate (Drug)
Unrelated UCBT for Blood Cancers
Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
干预措施: mycophenolate mofetil (Drug)
Unrelated UCBT for Blood Cancers
Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
干预措施: umbilical cord blood transplantation (Procedure)
Unrelated UCBT for Blood Cancers
Patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
干预措施: total-body irradiation (Radiation)
结局指标
主要结局
Number of Participants Who Were Alive at 1 Year Transplant Overall Survival
时间窗: at 1 year
Number of patients alive at 1 year after transplant.
次要结局
- Number of Participants Who Died Due to Transplant(At Month 6)
- Number of Participants With Platelet Engraftment(6 months)
- Number of Participants With Neutrophil Engraftment(Day 42)
- Number of Participants With Acute Graft-Versus-Host Disease(Day 100)
- Number of Participants With Chronic Graft-Versus-Host Disease(Year 1)
- Percentage Chimerism on Day 21(Day 21)
- Percentage Chimerism on Day 100(Day 100)
- Percentage Chimerism at 6 Months(Month 6)
- Percentage Chimerism at 2 Years(2 Years)
- Percentage Chimerism at 1 Year(1 Year)