QUILT-3.033: Haplo NK With SQ ALT-803 for Adults With Relapsed or Refractory AML

Inclusion Criteria:

- Diagnosis of acute myeloid leukemia (AML) and meets one of the following disease
criteria:

- Primary induction failure:

- De novo AML - no CR after 2 or more chemotherapy induction attempts

- Secondary AML (from MDS or treatment related): no CR after 1 or more
chemotherapy induction attempts

- Relapse after chemotherapy: not in CR after 1, 2, or 3 re-induction attempts

*** Patients > 60 years of age, the 1 cycle of chemotherapy is not required

- Relapse after hematopoietic stem cell transplant:

- Relapse must have occurred > 18 months after transplant

- No re-induction required and no more than 1 re-induction attempt is allowed.

- Notes:

1. For hypomethylating agents (i.e. decitabine, azacititdine) to count as an
induction/re-induction attempt, the patient must have completed a minimum of 3
monthly cycles

2. For targeting agents (i.e. sorafenib) to count as an induction/re-induction
attempt, the patient must have completed a minimum of 1 month without attaining
CR

3. 7+3 followed by 5+2 counts as TWO induction attempts

4. Use of hydroxyurea is permitted to control blasts until Day -3 per Section 8.7

5. A history of AML related CNS involvement is allowed if CSF analysis is negative
on 2 test dates at least 2 weeks apart prior to study treatment. The use of
ongoing CNS maintenance therapy is allowed while on study.

- HLA-haploidentical related donor (aged 12 to 75 years) with donor/recipient match
based on a minimum of intermediate resolution DNA based Class I typing of the A and B
locus (at least 2/4 class I allele)

- Karnofsky Performance Status ≥ 60%

- Adequate organ function within 14 days of study registration (28 days for pulmonary
and cardiac) defined as:

- Creatinine: ≤ 2.0 mg/dL

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

- Pulmonary Function: oxygen saturation ≥ 90% on room air; PFT's required only if
symptomatic or prior known impairment - must have pulmonary function >50%
corrected DLCO and FEV1.

- Cardiac Function: 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 systemic immunosuppressive medications for at least
3 days prior to NK cell infusion (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

- 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

- Received any investigational agent within the 14 days before the start of study
treatment (1st dose of fludarabine)

- Prior ALT-803