Donor Peripheral Stem Cell Transplant and Donor Natural Killer Cell Transplant After Total-Body Irradiation, Thiotepa, Fludarabine, and Muromonab-CD3 in Treating Patients With Leukemia or Other Blood Diseases
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.
Graft Versus Host Disease
Biological: natural killer cell therapy
Drug: fludarabine phosphate
Genetic: gene expression analysis
Other: flow cytometry
Other: immunologic technique
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: in vitro-treated peripheral blood stem cell transplantation
Radiation: total-body irradiation
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Transplantation of Haploidentical CD34+ Purified Peripheral Blood Stem Cells With NK-Cell Add-Back Following Conditioning With Total Body Irradiation, Thiotepa, Fludarabine and OKT3|
- Risk of developing grades III-IV acute graft-vs-host disease (GVHD) [ Designated as safety issue: No ]
- Risk for mortality from infection before day 180 [ Designated as safety issue: No ]
- Risk for graft failure [ Designated as safety issue: No ]
- Risk for life-threatening infections [ Designated as safety issue: No ]
- Concentration of NK, NK-T, T-cells, and dendritic cell subsets in the CD34+ NK/NK-T-enriched graft [ Designated as safety issue: No ]
- Cytomegalovirus-specific T cells in product and donor graft [ Designated as safety issue: No ]
- Genotype and phenotype of donor killer cell immunoglobulin-like receptor expression according to time after hematopoietic stem cell transplantation (HSCT) [ Designated as safety issue: No ]
- Reconstitution of NK function according to time after HSCT [ Designated as safety issue: No ]
- Expression of NKG2 ligands of leukemic blasts [ Designated as safety issue: No ]
|Study Start Date:||December 2006|
|Study Completion Date:||July 2010|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
- 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.
- 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.
OUTLINE: Patients are stratified according to age (≤ 7 years vs > 7 years).
- Conditioning regimen: Patients 7 years of age or younger undergo total-body irradiation (TBI) twice daily on days -11 to -9. Patients over 7 years of age undergo TBI once on day -9. All patients receive thiotepa IV over 2 hours on days -8 and -7, fludarabine phosphate IV on days -6 to -3 and muromonab-CD3 on days -6 to 6. Patients with acute lymphoblastic leukemia or leukemia in the spinal fluid also receive methotrexate intrathecally prior to and after donor peripheral blood stem cell (PBSC) transplantation .
- Donor PBSC transplantation: Patients undergo donor PBSC transplantation comprising CD34+ purified PBSCs and natural killer (NK) cells on day 0.
Blood samples are collected in weeks 1-4, 6, 8, and 12. Analysis of samples includes quantitation of NK, NK-T, and T-cell subsets (CD3, CD4, and CD8) by flow cytometry; donor killer cell immunoglobulin-like receptor genotype and phenotype; interferon-gamma levels; and NK cytotoxicity. Samples are also analyzed by leukemic blast assay to determine if ligands that activate NK cells are expressed.
After completion of study therapy, patients are followed periodically.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00450983
|United States, Washington|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109-1024|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109-1023|
|Principal Investigator:||Ann Woolfrey, MD||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|