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
- 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
- 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
- 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
- To correlate immune reconstitution of the in vivo expanded haploidentical NK cells with
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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Month 6, 1 Year
Sarah Cooley, MD
Masonic Cancer Center, University of Minnesota
United States: Food and Drug Administration
|Masonic Cancer Center, University of Minnesota||Minneapolis, Minnesota 55455|