Decitabine and Vorinostat Conditioning Followed by CD3-/CD19- NK Cells Infusion for High Risk Myelodysplastic Syndromes

A single donor apheresis will be collected on day 15 of cycle 1, enriched for NK cells with
the large scale CliniMacs device (Miltenyi) and activated by overnight incubation with IL-2.
After washing, the final NK cell product will be divided in two, with half given fresh on day
17 of course #1 and half stored frozen until day 17 of course #2.

Clinical response will be formally assessed 4-6 weeks after the start of 2nd course based on
International Working Group (IWG) criteria; however, bone marrow evaluations will be
completed to assess for any sign of significant disease progression between cycle 1 and 2.

Inclusion Criteria:

- Diagnosis of high risk myelodysplastic (MDS) that meets one of the following disease
classifications and is requiring treatment:

- International Prognostic Scoring System (IPSS) Category: INT-2 or High Risk

- WHO Classification: RAEB-1 or RAEB-2

- High risk cytogenetic abnormality as defined by presence of Monosomy 7, complex
karytope, or monosomal karyotype

- WHO Based Prognostic Scoring System (WPSS): High or Very High Risk

- Patients may be untreated or have had a maximum of 2 cycles of hypomethylating agents
(azacitidine or decitabine) without evidence of treatment failure as defined by
progression to more advanced MDS Who classification or AML. Patients must not have
received treatment for their MDS within 4 weeks of beginning the trial. Treatments
allowed prior to that time include azacitidine or decitabine and hematopoietic growth
factors. No prior AML-like induction therapy allowed.

- Age ≥ 18 years of age

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

- Available related HLA-haploidentical NK cell donor by at least Class I serologic
typing at the A&B locus

- Have acceptable organ function within 14 days of enrollment

- Ability to be off prednisone and other immunosuppressive drugs for at least 3 days
prior to the natural killer (NK) cell infusion

- Women of child bearing potential must agree to use effective methods of contraception

- Voluntary written consent

Exclusion Criteria:

- Pregnant or lactating.

- Prior 7 + 3 (cytarabine given continuously for 7 days with an anthracycline drug, such
as daunorubicin or idarubicin given for the 1st 3 days of treatment) or other AML-type
induction chemotherapy

- New progressive pulmonary infiltrates on screening chest x-ray or chest computed
tomography (CT) scan that has not been evaluated with bronchoscopy (when feasible)

- Uncontrolled bacterial or viral infections - chronic asymptomatic viral hepatitis is
allowed

- Pleural effusion moderate to large in size that are detectable on chest xray

- Known hypersensitivity to one or more of the study agents

- Prior hypomethylating treatment greater than 2 cycles or with documented treatment
failure

- Prior use of histone deacetylase inhibitors

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study in the opinion of the enrolling investigator

- Inability to swallow capsules

- Active human immunodeficiency virus (HIV)

- Other active and potentially life threatening malignancy excluding localized basal or
squamous cell skin cancer, cervical carcinoma in situ, superficial bladder cancer,
localized prostate cancer