Haploidentical Donor Natural Killer Cell Infusion With IL-15 in Acute Myelogenous Leukemia (AML)
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).
Acute Myelogenous Leukemia
Drug: Preparative Regimen
Biological: Intravenous Recombinant Human IL-15 (rhIL-15)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Haploidentical Donor Natural Killer (NK) Cell Infusion With Intravenous Recombinant Human IL-15 (rhIL-15) in Adults With Refractory or Relapsed Acute Myelogenous Leukemia (AML)|
- Maximum Tolerated/Minimum Efficacious Dose [ Time Frame: Day 42 ] [ Designated as safety issue: Yes ]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.
- Incidence of Expansion of Natural Killer Cells [ Time Frame: Day 14 after Infusion ] [ Designated as safety issue: No ]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.
- Treatment Related Mortality (TRM) [ Time Frame: Day 1 of Treatment until Day of Death ] [ Designated as safety issue: Yes ]In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
- Rate of CRp [ Time Frame: Day 28-42 ] [ Designated as safety issue: No ]defined as leukemia clearance (< 5% marrow blasts and no peripheral blood blasts) and neutrophil recovery without platelet recovery.
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||October 2016|
|Estimated Primary Completion Date:||November 2015 (Final data collection date for primary outcome measure)|
Experimental: IL-15 Patients with AML
Adults with Refractory or Relapsed Acute Myelogenous Leukemia (AML) treated with preparative regimen and Intravenous Recombinant Human IL-15 (rhIL-15)
Drug: Preparative Regimen
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)
Other Names:Biological: Intravenous Recombinant Human IL-15 (rhIL-15)
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
Other Name: IL-15
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01385423
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Jeffrey S Miller, MD||Masonic Cancer Center, University of Minnesota|