Umbilical Cord Blood Transplantation From Unrelated Donors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Engraftment of ANC and Platelets
研究概览
简要总结
This study is being done to determine how long it takes for the engraftment (recovery of blood cell counts) of umbilical cord stem cells and also how often engraftment of umbilical cord stem cells transplanted from an unrelated donor fails. Another purpose will be to document the rate of disease-free survival and the rate of relapse (a return of your disease or syndrome) as well as the incidence and severity of graft versus host disease (GvHD) following cord blood stem cell transplantation. GvHD is a complication of stem cell transplants in which white blood cells from the transplanted tissue (graft) attack the transplant recipient's body (host).
详细描述
PRIMARY OBJECTIVES:
I. Determine the kinetics of engraftment of umbilical cord blood (UCB) following transplantation into unrelated individuals.
II. Determine the incidence of non-engraftment and secondary graft failure when unrelated donor UCB cells are administered to patients receiving myeloablative, reduced intensity cytoreductive, or non-ablative conditioning regimens together with immunosuppressive therapy.
III. Determine the incidence and severity of graft-vs-host disease (GVHD) for patients receiving unrelated donor UCB grafts.
IV. Document the overall survival, disease-free-survival, and rates of relapse for UCB transplant recipients.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 2 Months 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Appropriate diagnosis: Patients must have a disease or syndrome amenable to therapy with hematopoietic stem cell transplantation. Diagnoses include, but are not limited to:
- •Congenital and Other Non-malignant Disorders:
- •Immunodeficiency disorders (e.g. Severe Combined Immunodeficiency, Wiskott-Aldrich Syndrome)
- •Congenital hematopoietic stem cell defects (e.g. Chediak-Higashi Syndrome, Congenital Osteopetrosis, Osteogenesis Imperfecta)
- •Metabolic disorders (e.g. Hurler's Syndrome)
- •Severe aplastic anemia
- •High-Risk Leukemia:
- •Acute Myelogenous Leukemia
- •Refractory to standard induction therapy (more than 1 cycle required to achieve remission)
- •Recurrent (in CR ≥ 2)
- •Treatment-related AML or MDS
- •Evolved from myelodysplastic syndrome
- •Presence of FLT3 abnormalities
- •FAB M6 or M7
- •Adverse cytogenetics
- •Myelodysplastic Syndrome
- •Acute Lymphoblastic Leukemia including T lymphoblastic leukemia:
- •Refractory to standard induction therapy (time to CR >4 weeks)
- •Recurrent (in CR ≥ 2)
- •WBC count >30,000/mcL at diagnosis
- •Age >30 at diagnosis
- •Adverse cytogenetics, such as t(9:22), t(1:19), t(4:11), and other MLL rearrangements.
- •Chronic Myelogenous Leukemia in accelerated phase or blast crisis
- •Biphenotypic or undifferentiated leukemia
- •Burkitt's leukemia or lymphoma
- •Lymphoma:
- •Large cell, Mantle cell, Hodgkin lymphoma refractory or recurrent, chemo-sensitive, and ineligible for an autologous stem cell transplant or previously treated with autologous SCT
- •Marginal zone or follicular lymphoma that is progressive after at least two prior therapies
- •Multiple Myeloma, recurrent following high-dose therapy and autologous SCT or ineligible for an autologous HSCT
- •Solid tumors, with efficacy of allogeneic HSCT demonstrated for the specific disease and disease status
- •Adequate organ function:
- •Cardiac - LVEF >45%, or shortening fraction >25%, Absence of congestive heart failure or conduction disturbances with high risk for sudden death
- •Pulmonary - DLCO (corrected for hemoglobin), FEV1 and FVC ≥ 50% predicted;
- •Renal - serum Cr < 1.5 times the upper limit of normal for age or GFR ≥ 50 ml/min/1.73m2
- •Hepatic - total bilirubin level < 2 times the upper limit of normal (except for patients with Gilbert's syndrome or hemolysis); if the primary disease process is causal, this criterion will be reconsidered. ALT, AST, and Alkaline phosphatase ≤ 5 times upper limit of normal.
- •Performance Status Karnofsky or Lansky score ≥ 70%.
- •Informed Consent must be obtained prior to initiating conditioning therapy.
- •Receipt of viable cord blood product(s), single or dual, must be confirmed with the stem cell processing laboratory prior to initiating conditioning therapy.
排除标准
- •Availability of 10/10 or 9/10 HLA-matched related or unrelated donor within a reasonable timeframe dictated by the clinical urgency of the transplant
- •Autologous HSCT < 6 months prior to proposed UCB transplant
- •Pregnant or breast feeding
- •Current uncontrolled infection
- •Evidence of HIV infection or positive HIV serology
研究组 & 干预措施
Full Intensity, TBI-based Conditioning
Full Intensity TBI-based Conditioning Total Body Irradiation 1200 cGy in fractions of 150 cGy days -8 or -7 to -4 Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses [to be completed 24 hours after final Cyclophosphamide dose] followed by Cord Blood Infusion Other names: TBI/Cy
干预措施: Total Body Irradiation 1200 cGy (Radiation)
Full Intensity, TBI-based Conditioning
Full Intensity TBI-based Conditioning Total Body Irradiation 1200 cGy in fractions of 150 cGy days -8 or -7 to -4 Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses [to be completed 24 hours after final Cyclophosphamide dose] followed by Cord Blood Infusion Other names: TBI/Cy
干预措施: Cyclophosphamide (Drug)
Full Intensity, TBI-based Conditioning
Full Intensity TBI-based Conditioning Total Body Irradiation 1200 cGy in fractions of 150 cGy days -8 or -7 to -4 Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses [to be completed 24 hours after final Cyclophosphamide dose] followed by Cord Blood Infusion Other names: TBI/Cy
干预措施: Mesna (Drug)
Full Intensity, TBI-based Conditioning
Full Intensity TBI-based Conditioning Total Body Irradiation 1200 cGy in fractions of 150 cGy days -8 or -7 to -4 Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses [to be completed 24 hours after final Cyclophosphamide dose] followed by Cord Blood Infusion Other names: TBI/Cy
干预措施: Cord Blood Infusion (Procedure)
Full Intensity, Chemo-based Conditioning
Full Intensity, Chemotherapy Conditioning Busulfan days -7 to -4 Recipients <5 years - 1 mg/kg/dose x 16 doses every 6 hours Recipients >/= 5 years - 0.8 mg/kg/dose x 16 doses every 6 hours Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses [to be completed 24 hours after final Cyclophosphamide dose] followed by Cord Blood Infusion Other names: Bu/Cy
干预措施: Cyclophosphamide (Drug)
Full Intensity, Chemo-based Conditioning
Full Intensity, Chemotherapy Conditioning Busulfan days -7 to -4 Recipients <5 years - 1 mg/kg/dose x 16 doses every 6 hours Recipients >/= 5 years - 0.8 mg/kg/dose x 16 doses every 6 hours Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses [to be completed 24 hours after final Cyclophosphamide dose] followed by Cord Blood Infusion Other names: Bu/Cy
干预措施: Mesna (Drug)
Full Intensity, Chemo-based Conditioning
Full Intensity, Chemotherapy Conditioning Busulfan days -7 to -4 Recipients <5 years - 1 mg/kg/dose x 16 doses every 6 hours Recipients >/= 5 years - 0.8 mg/kg/dose x 16 doses every 6 hours Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses [to be completed 24 hours after final Cyclophosphamide dose] followed by Cord Blood Infusion Other names: Bu/Cy
干预措施: Cord Blood Infusion (Procedure)
Full Intensity, Chemo-based Conditioning
Full Intensity, Chemotherapy Conditioning Busulfan days -7 to -4 Recipients <5 years - 1 mg/kg/dose x 16 doses every 6 hours Recipients >/= 5 years - 0.8 mg/kg/dose x 16 doses every 6 hours Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses [to be completed 24 hours after final Cyclophosphamide dose] followed by Cord Blood Infusion Other names: Bu/Cy
干预措施: Busulfan (Drug)
Reduced Intensity Chemotherapy
Reduced Intensity Chemotherapy Fludarabine 30 mg/m2/day x 5 doses days -6 to -2 Melphalan 140 mg/m2/day x 1 dose day -2 Cord Blood Infusion Other names: Flu/Mel
干预措施: Cord Blood Infusion (Procedure)
Reduced Intensity Chemotherapy
Reduced Intensity Chemotherapy Fludarabine 30 mg/m2/day x 5 doses days -6 to -2 Melphalan 140 mg/m2/day x 1 dose day -2 Cord Blood Infusion Other names: Flu/Mel
干预措施: Fludarabine (Drug)
Reduced Intensity Chemotherapy
Reduced Intensity Chemotherapy Fludarabine 30 mg/m2/day x 5 doses days -6 to -2 Melphalan 140 mg/m2/day x 1 dose day -2 Cord Blood Infusion Other names: Flu/Mel
干预措施: Melphalan (Drug)
Non-Myeloablative Conditioning
Fludarabine 40 mg/m2/day x 5 doses days -6 to -2 Cyclophosphamide 50 mg/kg/day x 1 dose day -6 Mesna 50 mg/kg/day with 20% loading dose with Cyclophosphamide dose followed by continuous infusion over 24 hours x 1 dose [to be completed 24 hours after Cyclophosphamide dose] Total Body Irradiation 200 cGy in a single fraction day -1 Cord Blood Infusion Other names: Flu/Cy/TBI
干预措施: Total Body Irradiation 200 cGy (Radiation)
Non-Myeloablative Conditioning
Fludarabine 40 mg/m2/day x 5 doses days -6 to -2 Cyclophosphamide 50 mg/kg/day x 1 dose day -6 Mesna 50 mg/kg/day with 20% loading dose with Cyclophosphamide dose followed by continuous infusion over 24 hours x 1 dose [to be completed 24 hours after Cyclophosphamide dose] Total Body Irradiation 200 cGy in a single fraction day -1 Cord Blood Infusion Other names: Flu/Cy/TBI
干预措施: Cyclophosphamide (Drug)
Non-Myeloablative Conditioning
Fludarabine 40 mg/m2/day x 5 doses days -6 to -2 Cyclophosphamide 50 mg/kg/day x 1 dose day -6 Mesna 50 mg/kg/day with 20% loading dose with Cyclophosphamide dose followed by continuous infusion over 24 hours x 1 dose [to be completed 24 hours after Cyclophosphamide dose] Total Body Irradiation 200 cGy in a single fraction day -1 Cord Blood Infusion Other names: Flu/Cy/TBI
干预措施: Mesna (Drug)
Non-Myeloablative Conditioning
Fludarabine 40 mg/m2/day x 5 doses days -6 to -2 Cyclophosphamide 50 mg/kg/day x 1 dose day -6 Mesna 50 mg/kg/day with 20% loading dose with Cyclophosphamide dose followed by continuous infusion over 24 hours x 1 dose [to be completed 24 hours after Cyclophosphamide dose] Total Body Irradiation 200 cGy in a single fraction day -1 Cord Blood Infusion Other names: Flu/Cy/TBI
干预措施: Fludarabine (Drug)
结局指标
主要结局
Engraftment of ANC and Platelets
时间窗: 42 days following the infusion of stem cells for ANC [If engraftment of ANC does not occur within 42 days, a subsequent transplant will be performed if a donor is available.]
The date of engraftment of ANC is the first of 3 consecutive days of ANC of 500 or higher based on daily CBC and Differential Counts. The date of engraftment of platelets is the first of three consecutive days of platelet counts of 20,000 or higher in the absence of platelet transfusions for a t least 7 days prior.
次要结局
- Incidence of acute graft-versus-host disease(At 30 days and 100 days after transplant from the date of transplant until the date of documented acute GvHD.)
- Incidence of chronic graft-versus-host disease(At 100 days, 6 months and yearly after transplant from the date of transplant until the date of documented graft failure or the subject's death up to 120 months.)
- Rate of non-engraftment and of secondary graft failure(At 30 days, 100 days, 6 months and yearly from the date of transplant until the date of documented graft failure or the subject's death up to 120 months.)
- Disease-free survival(At 30 days, 100 days, 6 months and yearly after transplant from the date of transplant until the date of documented graft failure or the subject's death up to 120 months.)
研究者
Omar Aljitawi
Professor - Department of Medicine, Hematology/Oncology (SMD)
University of Rochester