Unrelated or Partially Matched Allogeneic Donor Stem Cells for Lymphoma, Myeloma, and Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Number of Participants With Engraftment Failure
研究概览
简要总结
RATIONALE: Giving chemotherapy, such as cyclophosphamide and busulfan, and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells from bone marrow or umbilical cord blood may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving methotrexate and cyclosporine after 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 previously treated lymphoma, multiple myeloma, or chronic lymphocytic leukemia.
详细描述
OBJECTIVES:
- Determine if allogeneic stem cell transplantation using unrelated matched or related haploidentical donor bone marrow or unrelated matched cord blood results in timely, complete, and durable engraftment in patients with previously treated lymphoma, multiple myeloma, or chronic lymphocytic leukemia.
- Determine the incidence and grade of acute and chronic graft-versus-host disease in patients treated with this regimen.
- Determine if the augmented graft-versus-tumor effect accompanying unrelated or partially matched donor allogeneic transplant reduces the incidence of relapse in these patients.
OUTLINE:
- Preparative regimen: Patients receive cyclophosphamide IV over 2 hours on days -7 and -6 and undergo total-body irradiation (TBI) twice daily on days -4 to -1. Patients who are unable to undergo TBI receive busulfan IV or orally 4 times daily on days -9 to -6 and cyclophosphamide IV over 2 hours on days -5 to -2.
- Stem cell transplantation: All patients undergo unrelated matched bone marrow or umbilical cord blood transplantation or partially matched related allogeneic bone marrow transplantation on day 0.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive GVHD prophylaxis comprising methotrexate and cyclosporine. Patients may be enrolled in other protocols directed towards GVHD prophylaxis.
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
- •Donors will be <55 years of age and in good health as approved by the National Marrow Donor Program (NMDP) donor and collection centers. Related donors will be < 70 years of age.
- •Recipients will be <55 years, will have satisfactory organ function (excluding bone marrow) and will have a Karnofsky activity assessment >90% and will have:
- •Creatinine <2.0 mg/dl.
- •Bilirubin, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2 x normal.
- •Pulmonary function test and Carbon Monoxide Diffusing Capacity (DLCO) > 50% of normal.
- •Multi Gated Acquisition Scan (MUGA) >45% injection fraction.
- •Recipients with unrelated donor matched at the HLA A, B, DRBI loci, or if < 35 years mismatched at a single HLA A or B, or DRBI locus.
- •Umbilical cord blood (5) used as an unrelated stem cell source will provide > 2.0 x 10^7 cells/kg and will be matched at 4 - 6 of 6 HLA A, B, and DRBI loci. Cord blood grafts may include a single or pair of cord units depending on the cell dose.
- •Partially matched related donors will be at least haploidentical (matched at >3 of 6 HLA A, B, DRB1 loci).
- •Recipients will fall under one of the following disease categories
- •Chronic lymphocytic leukemia -- must have all three:
- •Rai Stage III/IV
- •Progression after previous Complete Response (CR) or Partial Response (PR) including purine antagonist (i.e. fludarabine).
- •Recent chemotherapy responsiveness
- •Advanced non-Hodgkin's lymphoma(NHL).
- •Low-grade NHL (Working Formulation A, B, C) following progression after initial therapy if asymptomatic at diagnosis (>CR2, >PR2; response duration < 1 year from last therapy) or if no CR was achieved (>PR1). At least one prior therapy of intermediate intensity (e.g. CHOP).
- •Mantle zone lymphoma after any progression following initial therapy (>CR1, > PR1). At least one prior therapy of intermediate intensity (e.g. CHOP).
- •Intermediate grade lymphoma (>PR2). Response duration <1 year from prior therapy.
- •High-grade Non-Hodgkin's Lymphoma (NHL) (IWF H, I, J) after initial therapy if >stage III at diagnosis; after any progression even if localized (stage I, II) at diagnosis with prior response duration < 1 year.
- •Recent chemotherapy responsiveness after treatment with > 3 intermediate intensity regimens.
- •Advanced Hodgkin's disease beyond PR2 (>CR3, >PR3).
- •Recent chemotherapy responsiveness
- •Multiple Myeloma (>CR2, >PR2) or after initial therapy if no prior PR.
- •Recent chemotherapy responsiveness
- •Recipients will sign informed consent approved by the Committee on the Use of Human Subjects at the University of Minnesota.
排除标准
- •No available histocompatible related donor; 2nd bone marrow transplant (BMT), HIV-1 positive; active uncontrolled infection; or resistant malignancy.
研究组 & 干预措施
Allogeneic Transplantation
Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
干预措施: busulfan (Drug)
Allogeneic Transplantation
Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
干预措施: cyclophosphamide (Drug)
Allogeneic Transplantation
Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
干预措施: Stem cell infusion (Biological)
Allogeneic Transplantation
Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
干预措施: Total body irradiation (Radiation)
结局指标
主要结局
Number of Participants With Engraftment Failure
时间窗: 3 Months
Graft failure is defined as not accepting donated cells. The donated cells do not make the new white blood cells, red blood cells and platelets.
Number of Participants With Neutrophil Engraftment
时间窗: Day 42
Time to 1st 3 consecutive days with absolute neutrophil count (ANC) \> 5 x 10\^8/L and percentage of patients with neutrophil recovery by day 42 (Cumulative incidence).
Number of Participants With Grade 3-4 Acute Graft-versus-host Disease
时间窗: Day 100
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Number of Participants With Persistence Disease
时间窗: 3 Years
the return of disease after its apparent recovery/cessation.
Number of Participants With Relapse of Malignancy
时间窗: 3 Years
the return of disease after its apparent recovery/cessation.
Number of Participants With 1 Year Overall Survival
时间窗: 1 year
The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. Overall survival will be defined as time from date enrollment to date of death or censored at the date of last documented contact for patients still alive.
Number of Participants With 2 Year Overall Survival
时间窗: 2 year
The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. Overall survival will be defined as time from date enrollment to date of death or censored at the date of last documented contact for patients still alive.
Number of Participants With Platelet Engraftment
时间窗: Day 180
Time to platelets \> 20,000 (first of 3 consecutive days) with no platelet transfusions for seven days and percentage of patients with platelet engraftment \>50,000 by day 100.
次要结局
- Number of Participants With of Chronic GVHD.(1 Year)