Haploidentical Natural Killer Cells to Treat Refractory or Relapsed Acute Myelogenous Leukemia (AML)
This is a phase II therapeutic study of related donor HLA-haploidentical NK-cell based therapy after a high dose of fludarabine/cyclophosphamide with denileukin diftitox preparative regimen for the treatment of poor prognosis acute myelogenous leukemia (AML).
Leukemia, Myelogenous, Acute
Biological: Natural Killer Cells
Drug: Denileukin diftitox
Procedure: Donor lymphapheresis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Adoptive Transfer of Haploidentical Natural Killer Cells to Treat Refractory or Relapsed AML MT2010-02|
- Expansion of Natural Killer Cells After Infusion [ Time Frame: Day 14 ] [ Designated as safety issue: No ]The primary objective of this study is to estimate the incidence of in vivo expansion of natural killer (NK) cells 14 days after infusion of an allogeneic donor product enriched for NK progenitors. Successful in vivo donor NK cell expansion will be defined by measuring an absolute circulating donor-derived NK cell count of >100 cells/ul in the patient's peripheral blood 14 days after infusion.
- Disease Response [ Time Frame: At least 4 weeks after last dose ] [ Designated as safety issue: No ]Disease response is defined as complete remission by morphologic criteria including <5% blasts in a moderately cellular or cellular marrow. Complete remission will also be correlated with NK cell expansion in vivo, IL-15 levels and donor/recipient KIR B genotyping, and Treg depletion.
- Disease Free Survival [ Time Frame: Month 6 ] [ Designated as safety issue: No ]Number of patients alive and disease free at 6 months.
- Incidence of Relapse [ Time Frame: Month 6 ] [ Designated as safety issue: No ]Number of patients who have had a relapse after obtaining a complete remission of their disease.
- Treatment Related Death [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]Number of patients who died within the first 100 days of treatment due to toxicity.
- Natural Killer Cell Expansion versus KIR Genotype versus Treg Depletion [ Time Frame: Day 14 ] [ Designated as safety issue: No ]Association between in vivo natural killer (NK) cell expansion and CRp with donor KIR genotype and Treg depletion.
|Study Start Date:||July 2010|
|Estimated Study Completion Date:||December 2012|
|Primary Completion Date:||October 2011 (Final data collection date for primary outcome measure)|
Experimental: Treated Patients
Patients are treated with donor natural killer cells, fludarabine, cyclophosphamide, Denileukin diftitox, Donor lymphapheresis and IL-2.
Biological: Natural Killer Cells
Given by infusion on Day 0. The product is T cell-depleted (CD3-) and B cell-depleted (CD19). Target dose for infusion is < or = 8 x 10^7 nucleated cells/kilogram.Drug: Fludarabine
Administered as a 1 hour intravenous infusion once a day for 5 doses beginning on day -6.
Other Name: FludaraDrug: Cyclophosphamide
Administered as a 2 hour intravenous infusion with high volume fluid flush and mesna per institutional guidelines on day -5 and -4 one hour after fludarabine infusion. (Day -4 administration may be omitted if patient has had a transplant in the previous 4 months.)
Other Name: CytoxanDrug: Denileukin diftitox
12 ug/kg/day will be administered on day -1 and day -2 intravenously.
Other Name: OntakProcedure: Donor lymphapheresis
Day -1 before planned NK cell infusion, the donor will undergo lymphapheresis (Removal of lymphocytes from donated blood, with the remainder of the blood retransfused into the donor).Drug: IL-2
Administered after NK cell infusion, 10 million units every other day for a total of 6 doses. (Patients weighing less than 45 kilograms will receive a dose of 5 million units/m^2 every other day for 6 doses).
Other Name: Interleukin-2
Patients achieving a complete remission and neutrophil recovery (ANC > 500) for at least 4 weeks will be considered for allogeneic transplant to prolong remission (independent of this study).
All patients, including those who go on to transplant, will be followed to determine disease free survival, treatment related mortality, and time to relapse.
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Jeffrey S. Miller, M.D.||Masonic Cancer Center, University of Minnesota|