This is a single center, "modified standard design" dose escalation study designed to determine the maximum tolerated, minimum efficacious dose (MTD/MED) of IL-15 (Intravenous Recombinant Human IL-15) and incidence of donor natural killer (NK) cell expansion by day +14 when given after haploidentical donor NK cells in patients with relapse or refractory acute myelogenous leukemia (AML).
Once the MTD/MED for IL-15 is determined, this cohort will be expanded to a total of 19 patients. The primary goal of this extended phase will be to establish a correlation of the clinical endpoint, CRp defined as leukemic clearance (\< 5% marrow blast and no peripheral blood blasts) and neutrophil recovery without platelet recovery, with in vivo expansion. 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Fludarabine 25 mg/m\^2 x 5 days start day -6, Cyclophosphamide 60 mg/kg x 2 days on day -5 and -4 (\*if \< 4 months from prior transplant, omit day -4 dose)
IL-15 at assigned dose (0.25, 0.5, 0.75 1, 2 and 3 mcg/kg for 3 to 6 patients) intravenously (IV) over 30 minutes once a day beginning day +1 and continuing for 12 doses
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States
Maximum Tolerated/Minimum Efficacious Dose
Determine the maximum tolerated, minimum efficacious dose (MTD/MED) of recombinant human IL-15; dose limiting toxicity (DLT) occurring during the first 42 days after the NK cell infusion; MED = if 2 of 3 patients or 4 of 6 patients has an in vivo NK cell count \>2500, then dose escalation with cease as it will be in the range of a biologic dose which may achieve the goal of in vivo expansion without pushing IL-15 doses higher to toxicity.
Time frame: Day 42
Incidence of Expansion of Natural Killer Cells
defined by measuring an absolute circulating donor-derived NK cell count of \>100 cells/μl in the patient's peripheral blood by day +14 after the NK cell infusion.
Time frame: Day 14 after Infusion
Treatment Related Mortality (TRM)
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Time frame: Day 1 of Treatment until Day of Death
Rate of CRp
defined as leukemia clearance (\< 5% marrow blasts and no peripheral blood blasts) and neutrophil recovery without platelet recovery.
Time frame: Day 28-42
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.