Cytokine Induced Memory-like NK Cell Adoptive Therapy After Haploidentical Donor Hematopoietic Cell Transplantation

Recipient Inclusion Criteria:

Refractory AML without complete remission (CR) after 2 or more cycles of induction therapy (primary induction failure), or AML relapsed after obtaining a CR and failed one or more cycles of re-induction therapy. Standard dose 10-day decitabine (20 mg/m2 daily IV x 10 days) or 7-day azacitidine (75-100 mg/m2 daily SC/IV x 7 days) will be considered as one cycle of induction therapy.
At least 18 years of age
Available HLA-haploidentical donor that meets the criteria in the protocol
Patients with known CNS involvement with AML are eligible provided that they have been treated and CSF is clear for at least 2 weeks prior to enrollment into the study. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment.
Karnofsky performance status > 60 %

Adequate organ function as defined below:

Total bilirubin < 2 mg/dl
AST(SGOT)/ALT(SGPT) < 3.0 x IULN
Creatinine within normal institutional limits OR creatinine clearance > 60 mL/min/1.73 m2 by Cockcroft-Gault Formula
Oxygen saturation ≥90% on room air and adjusted DLCO of at least 40%
Ejection fraction ≥40%
Able to be off of corticosteroids (10 mg or less of prednisone or equivalent doses of other systemic steroids are allowed) and any other immune suppressive medications beginning on Day -3
Women of childbearing potential must have a negative pregnancy test within 28 days prior to study registration. Female and male patients (along with their female partners) must agree to use two forms of acceptable contraception, including one barrier method, during participation in the study and throughout the DLT evaluation period.
Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Recipient Exclusion Criteria:

Relapsed after allogeneic transplantation.
Circulating blast count >30,000/uL by morphology or flow cytometry (cyto-reductive therapies including leukapheresis or hydroxyurea are allowed).
Uncontrolled bacterial or viral infections, or known HIV, Hepatitis B or C infection.
Presence of donor specific antibodies (DSA) with Mean Fluorescence Intensity (MFI) of >5000 as assessed by the single antigen bead assay, < 6 weeks prior to starting transplant conditioning
Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG suggestive of acute ischemia or active conduction system abnormalities.
New progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that have not been evaluated with bronchoscopy. Infiltrates attributed to infection must be stable/ improving after 1 week of appropriate therapy (4 weeks for presumed or proven fungal infections)
Known hypersensitivity to one or more of the study agents
Received any investigational drugs within the 14 days prior to the first day of transplant conditioning
Pregnant and/or breastfeeding

Donor Inclusion Criteria:

Related donor (sibling, offspring, or offspring of sibling)
At least 18 years of age
HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A&B locus.
In general good health, and medically able to tolerate leukapheresis required for harvesting the NK cells for this study.
Ability to understand and willingness to sign an IRB approved written informed consent document

Donor Exclusion Criteria:

Positive for hepatitis, HTLV, or HIV infection
Pregnant and/or breastfeeding