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
|ClinicalTrials.gov Identifier: NCT00450983|
Recruitment Status : Terminated
First Posted : March 22, 2007
Results First Posted : May 24, 2017
Last Update Posted : May 24, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Graft Versus Host Disease Leukemia Myelodysplastic Syndromes||Biological: muromonab-CD3 Biological: natural killer cell therapy Drug: fludarabine phosphate Drug: methotrexate Drug: thiotepa 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||Phase 2|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1 participants|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||December 2006|
|Actual Primary Completion Date :||July 2010|
|Actual Study Completion Date :||July 2010|
- Risk of Developing Grades III-IV Acute Graft-vs-host Disease (GVHD) [ Time Frame: Up to day 100 ]Count of participants with acute GVHD grades III-IV.
- Risk for Mortality From Infection Before Day 180 [ Time Frame: Up to day 180 ]Count of participant deaths from infection up to day 180.
- Risk for Graft Failure [ Time Frame: Engraftment documented day +20 ]Count of participant that had graft failure.
- Risk for Life-threatening Infections [ Time Frame: Up to day 100 ]Count of participants with life-threatening infections
- Concentration of NK, NK-T, T-cells, and Dendritic Cell Subsets in the CD34+ NK/NK-T-enriched Graft [ Time Frame: Up to 5 years ]
- Cytomegalovirus-specific T Cells in Product and Donor Graft [ Time Frame: Up to 5 years ]
- Genotype and Phenotype of Donor Killer Cell Immunoglobulin-like Receptor Expression According to Time After Hematopoietic Stem Cell Transplantation (HSCT) [ Time Frame: Up to 5 years ]
- Reconstitution of NK Function According to Time After HSCT [ Time Frame: Up to 5 years ]
- Expression of NKG2 Ligands of Leukemic Blasts [ Time Frame: Up to 5 years ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00450983
|United States, Washington|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109-1023|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109-1024|
|Principal Investigator:||Ann Woolfrey, MD||Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|