QUILT-3.034: Non-Myeloablative TCRa/b Deplete Haplo HSCT With Post ALT-803 for AML

Inclusion Criteria:

- Age ≥18 to ≤70 years

- Meets one of the following disease and risk categories:

- 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 (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 CR or CRi:
ELN-Intermediate I, Adverse, ELN-Intermediate-II. (18) (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 MEC) OR

- Progression after 4 cycles of hypomethylating agents

- The 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

- Karnofsky performance status ≥ 60% (appendix IV)

- Adequate organ function within 14 days of study registration (30 days for pulmonary
and cardiac) defined as:

- Hepatic: AST and ALT < 3 x upper limit of institutional normal

- Renal: estimated glomerular filtration rate (GFR) ≥ 40 mL/min/1.73m2

- Pulmonary: oxygen saturation ≥ 90% on room air with no symptomatic pulmonary
disease. If symptomatic or prior known impairment DLCOcor ≥ 40%.

- Cardiac: LVEF ≥ 40% by echocardiography, MUGA, or cardiac MRI, 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 pre-medications)

- 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

Exclusion Criteria:

- Acute leukemias of ambiguous lineage

- Allogeneic transplant for AML within the previous 6 months (no time limit for
autologous transplant)

- Active CNS disease - if a history of AML related CNS involvement, screening 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 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