This is a phase II multi-institutional therapeutic study of a non-myeloablative T cell receptor (TCR) alpha/beta depleted haploidentical transplantation with post-transplant immune reconstitution using ALT-803 for the treatment of high-risk myeloid leukemia (AML), treatment-related/secondary AML, and myelodysplastic syndrome (MDS).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
A reduced intensity conditioning starts on Day -6, (CY/FLU/TBI/TLI) followed by infusion of a TCRα/β-deplete haploidentical graft on Day 0. Two doses of ALT-803 are given initially (early) 1 week apart to facilitate NK cell expansion. ALT-803 maintenance (late) for immune reconstitution begins at Day 42 and consists of 4 weekly doses, followed by 4 weeks off. Up to four 8 week treatment courses are permitted. No post-transplant GVHD prophylaxis is administered unless the final donor cell product contains \> 2 x 105 α/β T cells/kg recipient weight.
Masonic Cancer Center
Minneapolis, Minnesota, United States
Incidence of disease response
Rate of donor neutrophil engraftment in the absence of disease at Day +28. Neutrophil engraftment is defined as absolute neutrophil count (ANC) ≥ 5 X 10 8 /L.
Time frame: Day 28
Disease Free Survival (DFS)
Incidence of disease free survival (DFS).
Time frame: 12 months
Treatment Related Mortality (TRM)
Incidence of treatment related mortality (TRM).
Time frame: 12 months
Disease Relapse
Incidence of disease relapse.
Time frame: 12 months
Grade II-IV acute Graft versus Host Disease (aGVHD)
Incidence of acute Graft versus Host Disease measured by the number of T-cells infused or NK cells engrafted causing GVHD syndrome.
Time frame: Day 100
Serious Adverse Events from ALT-803 (Early Schedule)
Incidence of serious adverse events from ALT-803 will be measured for an initial 2 doses, given one week apart.
Time frame: 1 Year
Serious Adverse Events from ALT-803 (Late Schedule)
Incidence of serious adverse events from ALT-803 will be measured for 16 doses, given over 4 weeks.
Time frame: 1 Year
Chronic Graft versus Host Disease (cGVHD)
Incidence of chronic Graft versus Host Disease will be measured by the number of T-cells infused or NK cells engrafted causing GVHD syndrome.
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Time frame: 1 year