Belinostat in Treating Patients With Myelodysplastic Syndromes
Condition: de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Secondary Myelodysplastic Syndromes
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: belinostat
Intervention description: Given IV
Intervention MeSH terms: Belinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well belinostat works in treating patients with
      myelodysplastic syndromes. Belinostat may stop the growth of cancer cells by blocking some of
      the enzymes needed for cell growth and by blocking blood flow to the cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed myelodysplastic syndromes (MDS)

               -  De novo or secondary MDS

          -  Patients with < 5 % bone marrow blasts must meet ≥ 1 of the following criteria:

               -  Symptomatic anemia with either hemoglobin < 10.0 g/dL or required RBC
                  transfusions within the past 3 months

               -  Thrombocytopenia with ≥ 2 platelet counts < 50,000/mm³ or significant hemorrhage
                  requiring platelet transfusions

               -  Neutropenia with ≥ 2 absolute neutrophil counts < 1,000/mm³

          -  No acute myeloid leukemia (≥ 20% bone marrow blasts)

          -  ECOG performance status 0-2

          -  Life expectancy > 12 weeks

          -  Bilirubin ≤ 1.5 times upper limit of normal (ULN)

          -  AST ≤ 2 times ULN

          -  Creatinine ≤ 2.0 mg/dL

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to PXD101

          -  No HIV positivity

          -  QTc interval ≤ 500 msec

          -  No long QT syndrome

          -  No significant cardiovascular disease, including any of the following:

               -  Unstable angina pectoris

               -  Uncontrolled hypertension

               -  Congestive heart failure related to primary cardiac disease

               -  Condition requiring anti-arrhythmic therapy

               -  Ischemic or severe valvular heart disease

               -  Myocardial infarction within the past 6 months

          -  No other uncontrolled serious medical condition (e.g., cardiac arrhythmias or
             diabetes)

          -  Recovered from prior therapy

          -  No more than 2 prior therapies for MDS

               -  Prior hematopoietic growth factors, androgens, and other supportive care agents
                  allowed and are not considered in the prior therapy total

          -  No prior allogeneic stem cell transplantation

          -  More than 4 weeks since prior radiotherapy or chemotherapy (6 weeks for nitrosoureas
             or mitomycin C)

          -  No prior histone deacetylase (HDAC) inhibitors for treatment of MDS

          -  More than 2 weeks since prior valproic acid or other HDAC inhibitors

          -  No other concurrent investigational agents

          -  No concurrent medication that may cause torsades depointes, including any of the
             following:

               -  Disopyramide

               -  Dofetilide

               -  Ibutilide

               -  Procainamide

               -  Quinidine

               -  Sotalol

               -  Bepridil

               -  Methadone

               -  Amiodarone hydrochloride

               -  Arsenic trioxide

               -  Cisapride

               -  Calcium-channel blockers (e.g., lidoflazine)

               -  Anti-infective agents (i.e., clarithromycin, erythromycin, halofantrine,
                  pentamidine, or sparfloxacin)

               -  Domperidone or droperidol

               -  Antipsychotic agents (i.e., chlorpromazine, haloperidol, mesoridazine,
                  thioridazine, or pimozide)