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Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD
Sponsor: Fred Hutchinson Cancer Center
Summary
This phase II trial is for patients with acute lymphocytic leukemia, acute myeloid leukemia, myelodysplastic syndrome or chronic myeloid leukemia who have been referred for a peripheral blood stem cell transplantation to treat their cancer. In these transplants, chemotherapy and total-body radiotherapy ('conditioning') are used to kill residual leukemia cells and the patient's normal blood cells, especially immune cells that could reject the donor cells. Following the chemo/radiotherapy, blood stem cells from the donor are infused. These stem cells will grow and eventually replace the patient's original blood system, including red cells that carry oxygen to our tissues, platelets that stop bleeding from damaged vessels, and multiple types of immune-system white blood cells that fight infections. Mature donor immune cells, especially a type of immune cell called T lymphocytes (or T cells) are transferred along with these blood-forming stem cells. T cells are a major part of the curative power of transplantation because they can attack leukemia cells that have survived the chemo/radiation therapy and also help to fight infections after transplantation. However, donor T cells can also attack a patient's healthy tissues in an often-dangerous condition known as Graft-Versus-Host-Disease (GVHD). Drugs that suppress immune cells are used to decrease the severity of GVHD; however, they are incompletely effective and prolonged immunosuppression used to prevent and treat GVHD significantly increases the risk of serious infections. Removing all donor T cells from the transplant graft can prevent GVHD, but doing so also profoundly delays infection-fighting immune reconstitution and eliminates the possibility that donor immune cells will kill residual leukemia cells. Work in animal models found that depleting a type of T cell, called naïve T cells or T cells that have never responded to an infection, can diminish GVHD while at least in part preserving some of the benefits of donor T cells including resistance to infection and the ability to kill leukemia cells. This clinical trial studies how well the selective removal of naïve T cells works in preventing GVHD after peripheral blood stem cell transplants. This study will include patients conditioned with high or medium intensity chemo/radiotherapy who can receive donor grafts from related or unrelated donors.
Official title: A Phase II Study Evaluating Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors for Prevention of GVHD
Key Details
Gender
All
Age Range
Any - 60 Years
Study Type
INTERVENTIONAL
Enrollment
84
Start Date
2015-03-23
Completion Date
2025-05-01
Last Updated
2026-06-01
Healthy Volunteers
Yes
Conditions
Interventions
Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HSCT
Cyclophosphamide
Given IV
Fludarabine Phosphate
Given IV
Laboratory Biomarker Analysis
Correlative studies
Methotrexate
Given IV
Mycophenolate Mofetil
Given IV and PO
Peripheral Blood Stem Cell Transplantation
Undergo PBSCT with GCSF-mobilized CD34-enriched PBSC
Peripheral Blood Stem Cell Transplantation
Undergo PBSCT with CD45RA-depleted cells
Tacrolimus
Given IV or PO
Thiotepa
Given IV
Total-Body Irradiation
Undergo TBI
Locations (2)
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States