Decitabine and Vorinostat Conditioning Followed by CD3-/CD19- NK Cells Infusion for High Risk Myelodysplastic Syndromes
Condition: Myelodysplastic Syndrome
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: Decitabine; Vorinostat; Interleukin-2; Natural killer (NK) cells
Intervention description: administered intravenous (IV), 10 mg/m^2/day over 1 hour on days 1-5.; 200 mg by mouth (PO) twice a day on days 6-15; 6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17; infusion intravenously (IV) over 15 to 60 minutes day 17
Intervention MeSH terms: Decitabine; Interleukin-2; Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: high risk myelodysplastic syndrome; natural killer cells

Summary:

      This is a Phase II therapeutic trial combining Decitabine days 1-5 with oral Vorinostat twice
      daily days 6-15 followed by a single infusion of CD3-/CD19- enriched donor natural killer
      (NK) cells on day 17 and a short course of Interleukin-2 (IL-2) to facilitate NK cell
      survival and expansion. Two courses of treatment will be given separated by 6-8 weeks. The
      intent is to administer all treatment in the outpatient setting.
    

Eligibility criteria:

        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