Vorinostat in Combination With Azacitidine in Patients With Newly-Diagnosed Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS)
Condition: Leukemia
MeSH terms: Leukemia; Preleukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
Intervention: Vorinostat; Azacitidine
Intervention description: 200 mg by mouth three (3) times per day with food for 5 days (Days 1 - 5); 75 mg/m^2/day given intravenously over 15 - 30 minutes daily for 5 days (Days 1 - 5)
Intervention MeSH terms: Azacitidine; Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 110.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Leukemia; Acute Myelogenous Leukemia; AML; Myelodysplastic Syndrome; MDS; Vorinostat; SAHA; Suberoylanilide Hydroxamic Acid; MSK-390; Zolinza; Azacitidine; 5-Azacitidine; 5-Aza; Vidaza; 5-AZC; AZA-CR; Ladakamycin; NSC-102816

Summary:

      The goal of this clinical research study is to learn if the combination of azacitidine and
      vorinostat can help to control AML or MDS better than azacitidine alone. The safety of this
      drug combination will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with newly diagnosed AML or MDS (Intermediate 1 or higher risk)

          2. Patient must have at least one of the following: a. Creatinine >/= 2 mg/dL; b. total
             Bilirubin >/= 2 mg/dL; c.ECOG Performance Status equal to 3 or 4; and d. is ineligible
             for participation on a protocol of higher priority

          3. Patients must provide written informed consent.

          4. Patients must be age > 18 years due to lack of safety information with these agents in
             children.

          5. Patient agrees to: 1) Use 2 adequate methods of contraception to prevent pregnancy
             (either 2 barrier methods or a barrier method plus a hormonal contraceptive method) or
             2) abstain from heterosexual activity throughout the study starting with Visit 1.

          6. Female patients of childbearing potential should have a negative pregnancy test
             (serum) within 72 hrs. of study enrollment.

        Exclusion Criteria:

          1. Patients must not have the favorable cytogenetic abnormalities of inv (16), t (16;16),
             t (8;21), or t (15;17).

          2. Patients receiving any anti-leukemic therapy with the exception of Hydroxyurea prior
             to study enrollment. Prior growth factor therapy is acceptable. Hydroxyurea could be
             used at the discretion of the treating physician. A single or a two day dose of
             cytarabine (up to 3 g/m^2) for emergency use is allowed as prior therapy.

          3. Patient has a prior history of treatment with HDAC inhibitors. Patients who have
             received valproic acid (VPA) for the treatment of seizures may be enrolled on this
             study, but must not have received VPA within 30 days of study enrollment.

          4. Patient is unable to take and/or tolerate oral medications on a continuous basis,
             examples include patients on a ventilator, or have altered mental status that
             precludes safe oral route of administration.

          5. Patient has active hepatitis A, B, or C infection.

          6. Patient is pregnant or breast-feeding.

          7. Patient has a known allergy or hypersensitivity to any component of vorinostat or
             azacitidine.

          8. History of any psychiatric condition that might impair the patient's ability to
             understand or to comply with the requirements of the study or to provide informed
             consent.