Bortezomib and Vorinostat in Treating Patients With High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia

Inclusion Criteria

• •Disease Specific Criteria: Pathologic Diagnosis must be confirmed by University of Minnesota Hematopathology
• •Myelodysplastic Syndrome (MDS): By IPSS Category: INT-2 or High risk, By WHO Classification: RAEB-1 or RAEB-2,By cytogenetics: High Risk Cytogenetic Abnormality Present as defined by the presence Monosomy 7 or complex karyotype. Patients will be eligible after progressing through standard therapy with either Azacitidine or Decitabine. Patients with a history of 5q minus syndrome may be eligible after progressing through treatment with Lenalidomide.
• •Acute Myelogenous Leukemia (AML): Histologic subtypes M0,M1,M2,M4,M5,M6,M7 are eligible and must meet one of the three criteria below:
• •* Refractory Disease/Induction Failure: Failure to achieve initial remission after 2 lines of induction therapy.
• •* Relapsed Disease
• •* Newly diagnosed/untreated AML: Patients who are not able to tolerate potentially curative conventional induction chemotherapy due to advanced age, end organ limitations, or performance status limitation will be eligible.
• •Additionally, those that refuse conventional induction therapy will be eligible.
• •Patients must have relatively stable bone marrow function during the week prior to enrollment on the study. White Blood cells (WBC) may be controlled with hydrea. Rapid WBC doubling not responsive to control with hydrea would indicate unstable bone marrow function. Ideally WBC should be \< 15 X 10\^3 /dl at time of study enrollment.
• •Age \>18 years
• •Karnofsky performance status \> or = 60%
• •Have acceptable organ function as defined within 28 days of enrollment:
• •* Hematologic: hemoglobin \> 8 g/dL, and platelets \> 20k. (Patients may receive transfusions of either peripheral red blood cells (PRBC) or platelets to achieve these levels)
• •* Renal: creatinine \< or = 2.0 mg/dL or creatinine clearance \> or = 40 ml/min
• •* Hepatic: ALT, AST \< or = 2.5 x upper limit of normal and total bilirubin \< or = 1.5 X ULN
• •* Cardiac: left ventricular ejection fraction \> 40% (testing required for all patients. For those with prior cardiac history (defined as prior stent or bypass surgery) a stress test within 1 month prior to proceeding with the study will be required. A cardiology consult will be required for those with prior documented cardiac disease or those with any significant EKG/ECHO abnormalities found on screening tests.
• •Patients must not have received treatment for their myeloid disorder within 2 weeks of beginning the trial. Treatments include the use of chemotherapy, hematopoietic growth factors, and biologic therapy such as monoclonal antibodies. The exception is the use of hydroxyurea for patients with an elevated WBC. Given the relatively slower expected clinical response with the study drugs, patients may continue to receive hydroxyurea through the first cycle of therapy.
• •Must have recovered from clinically significant toxicities from previous therapies.
• •Women of child bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device \[IUD\], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment. In addition, women of childbearing potential must have a negative serum pregnancy test b-hCG within 72 hours prior to receiving the first dose of therapy. Sexually active men must agree to use barrier contraceptive for the duration of treatment.
• •Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• •Treatment History Criteria: Patients who have relapsed after allogeneic stem cell transplantation are eligible.