NCT00450983终止2 期
Transplantation of Haploidentical CD34+ Purified Peripheral Blood Stem Cells With NK-Cell Add-Back Following Conditioning With Total Body Irradiation, Thiotepa, Fludarabine and OKT3
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Risk of Developing Grades III-IV Acute Graft-vs-host Disease (GVHD)
研究概览
简要总结
RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell and donor natural killer cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When certain 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. Removing the T cells from the donor cells before transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving a donor peripheral stem cell transplant and a donor natural killer cell transplant after total-body irradiation, thiotepa, fludarabine, and muromonab-CD3 works in treating patients with leukemia or other blood diseases.
详细描述
OBJECTIVES:
Primary
- Determine the effect of haploidentical donor CD34+ purified peripheral blood stem cells and donor natural killer (NK) cells on the risk of developing grades III-IV acute graft-vs-host disease in patients with leukemia or other hematologic diseases.
Secondary
- Determine the risk for mortality from infection before day 180 in patients treated with this regimen.
- Determine the risk for graft rejection in patients treated with this regimen.
- Determine the risk for life-threatening infections in patients treated with this regimen.
- Determine the concentration of subsets of NK, NK-T, T cells, and dendritic cells in the CD34+ NK/NK-T-enriched graft.
- Determine cytomegalovirus-specific T-cells in product and donor graft.
- Determine the genotype and phenotype of donor killer cell immunoglobulin-like receptor expression according to time after hematopoietic stem cell transplantation (HSCT).
- Determine the reconstitution of NK function according to time after HSCT.
- Determine the expression of NKG2 ligands of leukemic blasts.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Diagnosis of 1 of the following life-threatening hematological malignancies:
- •Acute lymphoblastic leukemia meeting 1 of the following criteria:
- •Advanced beyond first remission
- •In first remission with high-risk prognostic features, including any of the following:
- •Philadelphia chromosome-positive disease
- •Chromosome 11q23 abnormality
- •Hypodiploid
- •Failed to achieve first remission within 1 month after induction
- •Acute myeloid leukemia (AML) meeting 1 of the following criteria:
- •Advanced beyond first remission
- •First remission with high-risk prognostic features, including any of the following:
- •Chromosome 11q23 abnormality
- •Chromosome del 7q
- •Secondary AML
- •Failed to achieve first remission within 1 month after induction
- •Myelodysplastic syndromes with International Prognostic Score > 1
- •Chronic myelogenous leukemia in accelerated or blastic phase
- •No active CNS disease
- •No suitable HLA-matched related or unrelated donor available
- •Haploidentical family member available as donor of partially HLA-matched peripheral blood stem cells
- •Least degree of mismatch to HLA-A, B, C, DRB1, and DQB1
- •No mismatch for a single HLA-A, B, C, DRB1, or DQB1 antigen
- •Donor killer cell immunoglobulin-like receptor ligand group expression preferably different than patient
- •PATIENT CHARACTERISTICS:
- •LVEF ≥ 45%
- •DLCO ≥ 60% of predicted
- •AST and ALT ≤ 2 times upper limit of normal (ULN) (unless due to malignancy)
- •Bilirubin ≤ 2 times ULN (unless due to malignancy)
- •No life expectancy < 6 months due to coexisting disease other than the malignancy
- •No active infection (e.g., polymerase chain reaction [PCR] evidence for cytomegalovirus, human herpes virus 6, or invasive fungal infection)
- •No prior infections without evidence of resolution by PCR or imaging studies within the past 2 months
- •No hypersensitivity to murine antibodies
- •No known HIV positivity
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •PRIOR CONCURRENT THERAPY:
- •No prior marrow transplantation with total body irradiation > 400 cGy
- •No concurrent therapies for seizure disorder
- •No growth factors for 21 days after transplantation
排除标准
- 未提供
结局指标
主要结局
Risk of Developing Grades III-IV Acute Graft-vs-host Disease (GVHD)
时间窗: Up to day 100
Count of participants with acute GVHD grades III-IV.
次要结局
- Risk for Mortality From Infection Before Day 180(Up to day 180)
- Risk for Graft Failure(Engraftment documented day +20)
- Risk for Life-threatening Infections(Up to day 100)
- Concentration of NK, NK-T, T-cells, and Dendritic Cell Subsets in the CD34+ NK/NK-T-enriched Graft(Up to 5 years)
- Cytomegalovirus-specific T Cells in Product and Donor Graft(Up to 5 years)
- Genotype and Phenotype of Donor Killer Cell Immunoglobulin-like Receptor Expression According to Time After Hematopoietic Stem Cell Transplantation (HSCT)(Up to 5 years)
- Reconstitution of NK Function According to Time After HSCT(Up to 5 years)
- Expression of NKG2 Ligands of Leukemic Blasts(Up to 5 years)
研究者
Ann Woolfrey
Principal Investigator
Fred Hutchinson Cancer Center
研究点 (2)
Loading locations...
相似试验
已完成
2 期
Donor Stem Cell Transplant in Treating Patients With Hematologic CancerMyelodysplastic SyndromesMyelodysplastic/Myeloproliferative DiseasesLymphomaLeukemiaNCT00054327Case Comprehensive Cancer Center34
进行中（未招募）
2 期
Donor Peripheral Stem Cell Transplant in Treating Patients With Advanced Hematologic Cancer or Other DisordersMyelodysplastic SyndromesMyelodysplastic/Myeloproliferative DiseasesPrecancerous/Nonmalignant ConditionChronic Myeloproliferative DisordersGraft Versus Host DiseaseMultiple Myeloma and Plasma Cell NeoplasmLymphomaLeukemiaNCT00544115City of Hope Medical Center260
已完成
1 期
Donor Stem Cell Transplant in Treating Young Patients With Myelodysplastic Syndrome, Leukemia, Bone Marrow Failure Syndrome, or Severe Immunodeficiency DiseaseSevere Congenital NeutropeniaCongenital Amegakaryocytic ThrombocytopeniaMyelodysplastic SyndromesLeukemiaNCT00295971University of California, San Francisco21
终止
2 期
Peripheral Stem Cell Transplant in Treating Patients With High-Risk LeukemiaChronic Myeloproliferative DisordersMyelodysplastic/Myeloproliferative DiseasesLeukemiaNCT00066417National Heart, Lung, and Blood Institute (NHLBI)51
已完成
2 期
Allogeneic Transplantation From Related Haploidentical DonorsGraft Versus Host DiseaseNHLMDSCLLMalignancyBlood CancerHodgkin's DiseaseLeukemiaNCT00185692Stanford University16