Donor Stem Cell Transplant and ALT-803 in Treating Participants with High-Risk Acute Myeloid Diseases

Inclusion Criteria

• High-risk acute myeloid leukemia (AML) with predicted risk of relapse higher than 30%, which includes, but not limited to the following: * Patients in morphological remission (complete response 1 [CR1] or beyond) with minimal residual disease as quantified either by flow cytometry, or by cytogenetics or molecular markers. * Patients with the following karyotypes in morphological complete remission (CR) or complete remission with incomplete hematologic recovery (CRi): European LeukemiaNet (ELN)-Intermediate I, Adverse, ELN-Intermediate-II. (Examples include monosomal karyotype, complex karyotype, mutant p53, mutant RUNX1, mutant ASXL1, mutant FLT3-ITD, mutant DNMT3A, inversion 3, T(6:9), KIT mutated core binding factor AML)
• Treatment-related AML and secondary AML in morphological remission (CR1 or beyond) with minimal residual disease as quantified either by flow cytometry, or by cytogenetics or molecular markers
• Myelodysplastic syndrome (MDS) with < 5% blasts by morphology and meets at least one of the following: * Received intensive induction chemotherapy (i.e. 7+3 or mitoxantrone, etoposide, and cytarabine [MEC]) OR * Progression after 4 cycles of hypomethylating agents ** The donor and recipient must be human leukocyte antigen (HLA) identical for at least one haplotype (using high resolution deoxyribonucleic acid [DNA] based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1
• Karnofsky performance status >= 60%
• Within 14 days of study registration (30 days for pulmonary and cardiac): aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of institutional normal
• Within 14 days of study registration (30 days for pulmonary and cardiac): estimated glomerular filtration rate (GFR) >= 40 mL/min/1.73m^2
• Within 14 days of study registration (30 days for pulmonary and cardiac): oxygen saturation >= 90% on room air with no symptomatic pulmonary disease. If symptomatic or prior known impairment single breath carbon monoxide diffusing capacity (DLCOc) or >= 40%.
• Within 14 days of study registration (30 days for pulmonary and cardiac): left ventricular ejection fraction (LVEF) >= 40% by echocardiography or multigated acquisition (MUGA), no uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Able to be off prednisone or other immunosuppressive medications for at least 3 days prior to transplant (excluding preparative regimen premedications)
• Sexually active females of child bearing potential and males with partners of child bearing potential must agree to use effective contraception during therapy and for 4 months after completion of therapy
• Voluntary written consent prior to the performance of any research related procedures
• DONORS: HLA-haploidentical related donor (aged 18 to 75 years) where donor and recipient must be HLA identical for at least one haplotype (using high resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1
• DONORS: Body weight of at least 40 kilograms
• DONORS: In general good health as determined by the medical provider
• DONORS: Hemoglobin within 10% of upper and lower limit of normal range of test (gender based for hemoglobin)
• DONORS: White blood cells (WBC) within 10% of upper and lower limit of normal range of test (gender based for hemoglobin)
• DONORS: Platelets within 10% of upper and lower limit of normal range of test (gender based for hemoglobin)
• DONORS: ALT < 2 x upper limit of normal
• DONORS: Serum creatinine < 1.8 mg/dl
• DONORS: Performance of a donor infectious disease screen panel including cytomegalovirus (CMV) antibody, hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, human immunodeficiency virus (HIV) 1/2 antibody, human T-cell leukemia-lymphoma virus (HTLV) 1/2 antibody, Treponema, and trypanosoma cruzi (T. Cruzi) plus hepatitis B virus (HBV), hepatitis C virus (HCV), West Nile virus (WNV), HIV by nucleic acid testing (NAT); or per current standard institutional donor screen – must be negative for HIV and active hepatitis B
• DONORS: Not pregnant - females of childbearing potential must have a negative pregnancy test within 7 days of mobilization start
• DONORS: Voluntary written consent prior to the performance of any research related procedure

Exclusion Criteria

• Acute leukemias of ambiguous lineage
• Allogeneic transplant for AML within the previous 6 months (no time limit for autologous transplant)
• Active central nervous system (CNS) disease – if a history of AML related CNS involvement, screening cerebrospinal fluid (CSF) analysis must be negative
• Pregnant or breastfeeding - The agents used in this study include those that fall under Pregnancy Category D - have known teratogenic potential. Women of child bearing potential must have a negative pregnancy test at screening
• Active autoimmune disease requiring systemic immunosuppressive therapy
• History of severe asthma and currently on systemic chronic medications (mild asthma requiring inhaled steroids only is eligible)
• New or progressive pulmonary infiltrates on screening chest x-ray or chest computed tomography (CT) scan unless cleared for study by pulmonary. Infiltrates attributed to infection must be stable/improving (with associated clinical improvement) after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections).
• Uncontrolled bacterial, fungal or viral infections including HIV-1/2 or active hepatitis C/B - chronic asymptomatic viral hepatitis is allowed
• Active concomitant second malignancy (i.e. has required treatment in the previous 6 months)
• Known hypersensitivity to any of the study agents
• Received any investigational drugs within the 14 days before 1st dose of fludarabine