Bortezomib for Low or Intermediate-1 Myelodysplastic Syndrome (MDS) With p65 Activation
Condition: Leukemia
MeSH terms: Preleukemia; Myelodysplastic Syndromes
Intervention: Bortezomib
Intervention description: 1.3 mg/m2 subcutaneously on days 1, 4, 8 and 11 of a 21 day cycle.
Intervention MeSH terms: Bortezomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Leukemia; Myelodysplastic syndrome; MDS; Low or intermediate-1; Bortezomib; Velcade; LDP-341; MLN341; PS-341

Summary:

      The goal of this clinical research study is to learn if bortezomib can help to control MDS.
      The safety of this drug will also be studied.

      Bortezomib is designed to block a protein that causes cells to grow. This may cause cancer
      cells to die.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Voluntary signed informed consent before performance of any study-related procedure
             not part of normal medical care, indicating that that the patient is aware of the
             investigational nature of the study in keeping with the policies of MD Anderson Cancer
             Center (MDACC) and with the understanding that consent may be withdrawn by the subject
             at any time without prejudice to future medical care.

          2. Presence of phosphorylated p65 NF-kB component in at least 5% of bone marrow cells

          3. Age >/= 18 years of age at time of signing consent

          4. Confirmed MDS by bone marrow biopsy according to World Health Organization (WHO) or
             French-American-British (FAB) criteria.

          5. Classification by the International Prognostic Score System (IPSS) as low or
             intermediate-1 risk MDS according to cytogenetics, blood cytopenias and % bone marrow
             blasts within 28 days of the first dose of treatment in this study.

          6. Patients must have received at least one prior therapy for MDS. Patients could have
             received transplant for MDS

          7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1 or 2.

          8. Adequate liver function: Total bilirubin </= 1.5 × the upper limit of normal (ULN),
             unless presence of Gilbert's Syndrome. Aspartate aminotransferase (AST) and alanine
             aminotransferase (ALT) </= 2.5 × ULN or </= 5.0 ULN if hepatic involvement is present
             as determined by the investigator

          9. Adequate renal function: Serum creatinine </= 2 mg/dL or a calculated creatinine
             clearance of >/= 50 mL/min (using the Cockcroft and Gault method).

         10. Male patients, even if surgically sterilized (ie, status postvasectomy), who agree to
             practice effective barrier contraception during the entire study treatment period and
             through 30 days after the last dose of study treatment, or agree to completely abstain
             from heterosexual intercourse.

         11. Female patients who are postmenopausal for at least 1 year before the Screening visit,
             or are surgically sterile, or if they are of childbearing potential, must have a
             negative pregnancy test within 72 hours of treatment start date and agree to practice
             2 effective methods of contraception, at the same time, from the time of signing the
             informed consent through 30 days after the last dose of study treatment, OR agree to
             completely abstain from heterosexual intercourse

         12. Willingness and ability to comply with scheduled visits, treatment plan, laboratory
             tests and other study procedures.

        Exclusion Criteria:

          1. Significant medical, psychiatric, cognitive or other conditions that may compromise
             the patient's ability to understand the patient information, to give informed consent,
             to comply with the study protocol, or to complete the study.

          2. Any severe concurrent disease or condition (including active, uncontrolled systemic
             infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac
             arrhythmia) that, in the judgment of the Investigator, would make the patient
             inappropriate for study participation.

          3. Pregnant or lactating females.

          4. Patient has >/= Grade 2 peripheral neuropathy

          5. Patient had myocardial infarction within 6 months prior to enrollment or has New York
             Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities. Prior to study entry, any ECG
             abnormality at screening must be documented by the investigator as not medically
             relevant.

          6. Patient has hypersensitivity to bortezomib, boron, or mannitol

          7. Current diagnosis of another malignancy within 2 years of enrollment, with the
             exception of complete resection of basal cell carcinoma or squamous cell carcinoma of
             the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.

          8. Treatment with other investigational agents, chemotherapy, or immunotherapy within 14
             days of the start of this trial and throughout the duration of this trial.

          9. Radiation therapy within 3 weeks before randomization. Enrollment of subjects who
             require concurrent radiotherapy (which must be localized in its field size) should be
             deferred until the radiotherapy is completed and 3 weeks have elapsed since the last
             date of therapy.