CD3/CD19 Depleted or CD3 Depleted/CD56 Selected Haploidentical Donor Natural Killer (NK) Cell Based Therapy for AML Patients Not in CR

This trial uses a Simon's two-stage design to estimate the complete remission rate at day +42
post NK cell infusion. The trial includes an initial randomized sub- study of 24 patients
during stage 1 to choose which of the enriched NK cell products (CD3-/CD19- versus
CD3-/CD56+) should be used to complete the trial based on successful in vivo NK cell
expansion. This parameter is defined as 40% donor DNA and 40% of lymphocytes are NK cells at
day 7 post infusion OR 20% donor DNA and 20% of lymphocytes are NK cells at day 14 post
infusion. Twelve patients will be randomized to each product.

Enrollment Plan:

Stage 1: Enroll 24 patients with 1:1 randomization for NK cell processing (CD3-/CD19- versus
CD3-/CD56+) Stage 2: Enroll an additional 17 patients using the optimal NK cell product
identified during stage 1.

If neither product achieves success at the end of stage 1, the study will stop and the
platform redesigned

Inclusion Criteria:

- Newly diagnosed with acute myelogenous leukemia (except acute promyelocytic leukemia)
and has failed one or two prior standard induction attempts. Failure is defined as:

- ≥ 30% bone marrow blasts with at least 20% cellularity at mid-cycle bone marrow biopsy
or residual AML on subsequent~ day 28 bone marrow biopsy by morphology, flow, PCR or
FISH

- Patients enrolling after only 1 failed induction attempt must meet at least one of the
following additional eligibility criteria of high risk: ≥ 60 years of age adverse
cytogenetics or molecular characteristics

- AML that progressed out of myelodysplastic syndrome (MDS) is eligible if the patient
did not receive treatment directed at the MDS

- HLA-haploidentical related donor (aged 12 to 70 years)

- ≥ 18, but < 75 years of age

- Karnofsky performance status ≥ 60%

- Adequate organ function within 14 days of study registration (30 days for pulmonary
and cardiac) as defined in section 4.5

- Ability to be off prednisone and other immunosuppressive drugs for at least 3 days
prior to the NK cell infusion (excluding preparative regimen pre-meds)

- No prior hematopoietic transplant

- Not pregnant or lactating

- Sexually active females of childbearing potential and males with partners of child
bearing potential must agree to use birth control

Exclusion Criteria:

- Pregnant or lactating as the treatments used in this study includes drugs that are FDA
Pregnancy Category D.

- Acute leukemias of ambiguous lineage

- AML that transformed from previously treated myelodysplastic syndromes

- Prior hematopoietic transplant

- New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan
that has not been cleared 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 - chronic
asymptomatic viral hepatitis is allowed

- Known hypersensitivity to one or more of the study agents used