A Pilot Study to Evaluate the Co-infusion of Ex Vivo Expanded Umbilical Cord Blood Progenitors With an Unmanipulated Cord Blood Graft in Patients Undergoing Umbilical Cord Blood Transplantation for Hematologic Malignancies

Fred Hutchinson Cancer Center4 个研究点分布在 1 个国家目标入组 23 人开始时间: 2006年4月最近更新: 2015年2月11日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Fred Hutchinson Cancer Center
入组人数: 23
试验地点: 4
主要终点: Severe (grades 3 and 4) acute GVHD

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This phase I multicenter feasibility trial is studying the safety and potential efficacy of infusing ex vivo expanded cord blood progenitors with one unmanipulated umbilical cord blood unit for transplantation following conditioning with fludarabine, cyclophosphamide and total body irradiation (TBI), and immunosuppression with cyclosporine and mycophenolate mofetil (MMF) for patients with hematologic malignancies. Chemotherapy, such as fludarabine and cyclophosphamide, and TBI given before an umbilical cord blood transplant stops the growth of leukemia cells and works to prevent the patient's immune system from rejecting the donor's stem cells. The healthy stem cells from the donor's umbilical cord blood help the patient's bone marrow make new red blood cells, white blood cells, and platelets. It may take several weeks for these new blood cells to grow. During that period of time, patients are at increased risk for bleeding and infection. Faster recovery of white blood cells may decrease the number and severity of infections. Studies have shown that counts are more likely to recover more quickly if increased numbers of cord blood cells are given with the transplant. We have developed a way of growing or "expanding" the number of cord blood cells in the lab so that there are more cells available for transplant. We are doing this study to find out whether or not giving these expanded cells along with one unexpanded cord blood unit is safe and if use of expanded cells can decrease the time it takes for white blood cells to recover after transplant. We will study the time it takes for blood counts to recover, which of the two cord blood units makes up the patient's new blood system, and how quickly immune system cells return

详细描述

PRIMARY OBJECTIVES:

I. Examine the safety and toxicity when ex vivo expanded cord blood cells are co-infused with a second non-human leukocyte antigen (HLA)-identical cord blood graft following myeloablative therapy in patients with hematologic malignancies.

II. Examine the in vivo persistence of the ex vivo expanded cord blood cells. The kinetics and durability of hematopoietic reconstitution (time to engraftment defined as the first of 2 consecutive days in which the absolute neutrophil count [ANC] > 500) will be determined and the relative contribution to engraftment of the expanded cord blood cells and the unmanipulated cord blood cells in early and long-term engraftment will be determined by donor chimerisms.

SECONDARY OBJECTIVES:

I. Estimate the incidence and severity of acute and chronic graft-versus-host disease (GVHD) in patients receiving Notch-expanded cord blood cells.

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: 6 Months 至 45 Years（Child, Adult）
性别: All
接受健康志愿者: 否

入选标准

•Patient has no existing 0-1 HLA-A, B, C, DRB1 and DQB1 matched related donor
•Acute Myeloid Leukemia:
•High risk first complete remission (CR1) as evidenced by preceding myelodysplastic syndromes (MDS), high risk cytogenetics (for example, monosomy 5 or 7, or HR as defined by referring institution treatment protocol), >= 2 cycles to obtain complete remission (CR), erythroblastic or megakaryocytic leukemia; >= second complete remission (CR2);
•All patients must be in CR as defined by hematologic recovery and < 5% blasts by morphology within the bone marrow and a cellularity of >= 15%;
•Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry (< 5% blasts) and, recovery of peripheral blood counts with no circulating blasts, may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures
•Acute lymphoblastic leukemia:
•High risk CR1 (for example, but not limited to: t(9;22), t(1;19), t(4;11) or other mixed-lineage leukemia (MLL) rearrangements, hypodiploid);
•> 1 cycle to obtain CR;
•All patients must be in CR as defined by hematologic recovery and < 5% blasts by morphology within the bone marrow and a cellularity of >= 15%;
•Patients in which adequate marrow/biopsy specimens can not be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry (< 5% blasts) and, recovery of peripheral blood counts with no circulating blasts, may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures
•Chronic Myelogenous Leukemia:
•Patients in blast crisis (BC) must receive therapy and must achieve accelerated phase (AP)/chronic phase (CP) in order to be eligible (patients who remain in BC are not eligible);
•If in first chronic phase, patient must have failed or be intolerant to imatinib mesylate
•Myelodysplasia (MDS):
•International Prognostic Scoring System (IPSS) Int-2 or high risk (Refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [RAEBt]) or refractory anemia with severe pancytopenia or high risk cytogenetics;
•Blasts must be < 10% morphologically in representative bone marrow aspirate (obtained < 2 weeks from enrollment)
•Lymphoblastic lymphoma, Burkitt's lymphoma, and other high-grade non-Hodgkin lymphoma (NHL) after initial therapy if stage III/IV in first partial remission (PR1) or after progression if stage I/II < 1 year; Stage III/IV patients are eligible after progression in complete response (CR)/partial response (PR)
•Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, lymphoplasmacytic lymphoma or follicular lymphoma that have progressed after at least two different prior therapies; patients with bulky disease (nodal mass greater than 5 cm) should be considered for debulking chemotherapy before transplant (these patients must be presented at Patient Care Conference [PCC] prior to enrollment given potential competing eligibility on autotransplant protocols)
•Mantle-cell lymphoma, prolymphocytic leukemia: Eligible after initial therapy in >= CR1 or >= PR1
•Large cell NHL > CR2/ > PR2:
•Patients in CR2/PR2 with initial short remission (< 6 months) are eligible;
•These patients must be presented at PCC prior to enrollment given potential competing eligibility on autotransplant protocols
•Multiple myeloma beyond PR2: Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or beta-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy
•Serum creatinine =< 2.0 mg/dL (adults) and creatinine clearance > 60 ml/min (pediatrics)
•Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL and symptomatic biliary disease will be excluded
•Diffusing capacity of the lung for carbon monoxide corrected (DLCOcorr) > 50% normal
•Left ventricular ejection fraction >= 45% or shortening fraction > 26%
•Karnofsky score >= 70% (adults) or Lansky score >= 50% (pediatrics)

排除标准

•Acute leukemia in relapse (>= 5% marrow blasts by morphology)
•Active central nervous system (CNS) leukemia involvement at the time of study enrollment (cerebrospinal fluid with > 5 white blood cells (WBC)/mm^3 AND malignant cells on cytospin)
•Chemotherapy refractory large cell lymphoma and high grade NHL (progressive disease after > 2 salvage regimens)
•Female patients who are pregnant or breastfeeding
•Karnofsky performance status < 70% (adults) or Lanksy score < 50% (pediatrics)
•Prior autologous or allogeneic stem cell transplant with myeloablative preparative regimen (If =< 18 years old, prior myeloablative transplant within the last 6 months)
•Uncontrolled viral, or bacterial infection at the time of study enrollment
•Active or recent (prior 6 months) invasive fungal infection without ID consult and approval
•Seropositive for human immunodeficiency virus (HIV)
•Consenting 5 of 6 or 6 of 6 HLA-matched related donor available
•Unable to provide informed consent
•Use of any other experimental drug within 28 days of baseline