Phase II 5-Azacytidine Plus VPA Plus ATRA
Condition: Myelodysplastic Syndrome; Acute Myelogenous Leukemia
MeSH terms: Leukemia; Preleukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Syndrome
Intervention: 5-Azacytidine (5-aza); Valproic Acid; All-Trans Retinoic Acid (ATRA)
Intervention description: Start at 75 mg/m^2 subcutaneously daily for 7 days.; 50 mg/kg daily by mouth for 7 days, same days as 5-aza.; 45 mg/m^2 orally daily (in two divided doses) for 5 days starting on day 3 of the administration of 5-aza and VPA.
Intervention MeSH terms: Azacitidine; Tretinoin; Valproic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 3 Years
Healthy volunteers: No
Keywords: Combination Chemotherapy; MDS; High-Risk Myelodysplastic Syndrome; AML; Acute myelogenous leukemia; valproic acid; VPA; Depakene; 5-azacytidine; 5-aza; Azacitidine; 5-AZC; Vidaza; AZA-CR; Ladakamycin; NSC-102816; All-trans retinoic acid; ATRA; Tretinoin; Vesanoid

Summary:

      5-aza is a chemotherapy drug with activity in leukemia and myelodysplastic syndromes (MDS).
      Researchers hope that valproic acid (VPA) and all-trans retinoic acid (ATRA)will increase the
      effects of 5-aza. The goal of this clinical research study is to find the highest safe dose
      of valproic acid (VPA) that can be given in combination with 5-azacytidine (5-aza) and
      all-trans retinoic acid (ATRA) in the treatment of AML and MDS. The safety and effectiveness
      of this combination therapy will also be studied.

      Additional blood and bone marrow samples will be requested. These samples will be used to
      evaluate the effect of the treatment on leukemic cells. In addition, any leftover blood and
      bone marrow samples that are collected at the start of the study and during the regularly
      scheduled evaluations to be sent for research studies. The research studies will examine
      changes in the blood and bone marrow cells that might help explain the causes of leukemia and
      MDS and how the combination of 5-aza, VPA, and ATRA works.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with refractory or relapsed: acute myelogenous leukemia (AML), and
             myelodysplastic syndrome (MDS) (bone marrow blasts > or = 10%) are eligible.

          -  Untreated patients older than 60 years of age with AML or MDS (bone marrow blasts > or
             = 10%) who refuse or are not eligible for front-line chemotherapy, are eligible.

          -  Performance status of < or = 2 by the Eastern Cooperative Oncology Group (ECOG) scale.

          -  Signed informed consent indicating that patients are aware of the investigational
             nature of this study in keeping with the policies of University of Texas M D Anderson
             Cancer Center (UTMDACC).

          -  Age > 2 years. Valproic acid has been associated with a higher rate of severe liver
             toxicity in children younger than 2 years.

          -  Patients must have been off chemotherapy for 2 weeks prior to entering this study and
             recovered from the toxic effects of that therapy, unless there is evidence of rapidly
             progressive disease. Use of hydroxyurea for patients with rapidly proliferative
             disease is allowed for the first two weeks on therapy.

          -  Adequate liver function (bilirubin of < 2mg/dL, SGPT < 3 * ULN) and renal function
             (creatinine < 2mg/dL).

          -  Women of childbearing potential must practice contraception. Men and women must
             continue birth control for the duration of the trial.

          -  Patients with relapsed /refractory disease with inv16, t(8;21) or t(15;17) are
             eligible.

        Exclusion Criteria:

          -  Nursing and pregnant females are excluded.

          -  Patients with active and uncontrolled infections are excluded.

          -  Patients already receiving valproic acid or receiving other anticonvulsants will be
             excluded.

          -  Untreated patients younger than 60 years will not be candidates for this study.

          -  Patients with untreated disease inv16, t(8;21) or t(15;17) will be excluded.