Omacetaxine in Patients With Intermediate-1 and Higher Risk Myelodysplastic Syndrome (MDS) Post Hypomethylating Agent (HMA) Failure
Condition: Leukemia
MeSH terms: Preleukemia; Myelodysplastic Syndromes
Intervention: Omacetaxine
Intervention description: 1.25 mg/m2 subcutaneously every 12 hours on Days 1-3 of every 28-day study cycle.
Intervention MeSH terms: Homoharringtonine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Leukemia; Myelodysplastic Syndrome; MDS; Omacetaxine; Synribo; Homoharringtonine

Summary:

      The goal of this clinical research study is learn if omacetaxine can help to control
      myelodysplastic syndrome (MDS). The safety of this drug will also be studied.

      This is an investigational study. Omacetaxine is FDA approved and commercially available for
      the treatment of chronic myelogenous leukemia (CML). It is investigational to use omacetaxine
      in patients with MDS. The study doctor can explain how the study drug is designed to work.

      Up to 80 participants will be enrolled in this study. All will take part at MD Anderson.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age >/= 18 years

          2. Diagnosis of MDS confirmed within 10 weeks prior to study entry according to WHO
             criteria. Patients are either not eligible for or choose not to proceed with a stem
             cell transplant.

          3. MDS classified as follows: RAEB-1 (5%-9% BM blasts); RAEB-2 (10%-19% BM Blasts); CMML
             (5%-19% BM blasts); RAEB-t (20%-29% BM blasts) AND/OR by IPSS: intermediate-1 and high
             risk patients.

          4. No response, progression, or relapse (according to 2006 IWG criteria) following at
             least 4 cycles of either azacitidine or decitabine, which were completed within the
             last 2 years - AND/OR - intolerance to azacitidine or decitabine defined as
             drug-related >/= grade 3 hepatic or renal toxicity leading to treatment
             discontinuation during the preceding 2 years.

          5. Eastern Cooperative Oncology Group (ECOG) performance status of </= 2.

          6. Willing to adhere to and comply with all prohibitions and restrictions specified in
             the protocol.

          7. Patient (or patient's legally authorized representative) must have signed an informed
             consent document indicating that the patient understands the purpose of and procedures
             required for the study and is willing to participate in the study.)

        Exclusion Criteria:

          1. Uncontrolled intercurrent illness including, but not limited to, symptomatic
             congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.

          2. Active infection not adequately responding to appropriate antibiotics (i.e. ongoing
             temperatures of >/= 38 degree Celsius).

          3. Total bilirubin >/= 1.5 mg/dL and not related to hemolysis or Gilbert's disease.
             Patients with total bilirubin >/= 1.5 mg/dL to 3 mg/dL are eligible if at least 75% of
             the bilirubin is indirect.

          4. Alanine transaminase (ALT/SGPT) or aspartate transaminase (AST/SGOT) >/= 2.5 x the
             upper limit of normal.

          5. Serum creatinine > 1.5 mg/dL.

          6. Female patients who are pregnant or lactating.

          7. Patients with reproductive potential who are unwilling to following contraception
             requirements (including condom use for males with sexual partners, and for females:
             prescription oral contraceptives [birth control pills], contraceptive injections,
             intrauterine devices [IUD], double-barrier method [spermicidal jelly or foam with
             condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the
             study.

          8. Female patients with reproductive potential who do not have a negative urine or blood
             beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.

          9. Patients receiving any other concurrent investigational agent or chemotherapy,
             radiotherapy, or immunotherapy.

         10. Prior hydroxyurea for control of leukocytosis or use of hematopoietic growth factors
             (eg, G-CSF, GM-CSF, procrit, aranesp, thrombopoietins) is allowed at any time prior to
             or during study if considered to be in the best interest of the patient.

         11. Psychiatric illness or social situation that would limit the patient's ability to
             comply with study requirements.