Reduced Intensity Haploidentical Hematopoietic Stem Cell Transplantation (HSCT) Supplemented With Donor Natural Killer (NK) Cell Infusions in Patients With High Risk Myeloid Malignancies Who Are Unsuitable for Fully Myeloablative Transplantation
OBJECTIVES:
Primary
- To determine the disease-free survival at 6 months and 1 year in patients with
high-risk myeloid malignancies who undergo a reduced-intensity haploidentical
hematopoietic stem cell transplantation (HSCT) supplemented with donor natural killer
(NK) cells.
Secondary
- To evaluate the in vivo expansion of a donor CD3- CD19- selected NK cell product
administered after a preparative regimen of cyclophosphamide, fludarabine, and total
body irradiation (TBI) and HSCT in these patients.
- To determine the rate of graft failure defined by absolute neutrophil count (ANC) <
500/mm³ by day 28.
- To determine the incidence of grade III-IV acute graft-versus-host disease (GVHD) at 6
months.
- To determine the rate of treatment-related mortality at day 100.
- To determine the incidence of chronic GVHD at 12 months.
- To determine the incidence of disease relapse at 12 months.
- To determine the incidence of post-transplant lymphoproliferative disorder at 12
months.
Correlative
- To correlate immune reconstitution of the in vivo expanded haploidentical NK cells with
clinical outcomes.
OUTLINE: This is an open-label study.
Patients receive fludarabine intravenous (IV) over 1 hour on days -18 to -14 and
cyclophosphamide IV over 2 hours on days -16 and -15. Patients receive cyclosporin A on Day
-15 through Day -8. Patients undergo total body irradiation on day -13. Patients then
receive an infusion of donor natural killer cells on day -12 and interleukin-2
subcutaneously on alternating days between days -12 to -2. Patients receive thymoglobulin
(ATG) and undergo allogeneic peripheral blood stem cell transplantation on day 0.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Disease-free survival
Month 6, 1 Year
No
Sarah Cooley, MD
Principal Investigator
Masonic Cancer Center, University of Minnesota
United States: Food and Drug Administration
2004LS042
NCT00303667
January 2005
January 2015
Name | Location |
---|---|
Masonic Cancer Center, University of Minnesota | Minneapolis, Minnesota 55455 |