Study of LBH589 for Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
Condition: Myelodysplastic Syndrome
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: LBH589
Intervention description: 20 mg capsules by mouth 3 times a week for 3 weeks in a 28-day cycle.
Intervention MeSH terms: Panobinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Low or Intermediate-1 Risk Myelodysplastic Syndrome; MDS; Cancer; LBH589

Summary:

      The goal of this clinical research study is to learn if LBH589 can help to control lower-risk
      (low or intermediate-1 risk) MDS. The safety of this drug will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with intermediate-1 risk MDS or transfusion dependent low risk MDS by the
             IPSS classification. Patient must have one or more cytopenia as defined by IPSS
             (Cytopenias are defined as an absolute neutrophil count < 1800 K/uL; or hemoglobin <
             10 g/dl or platelets < 10^5 K/uL).

          2. Signed informed consent indicating that patients are aware of the investigational
             nature of this study prior to participation in the study and any related procedures
             being performed.

          3. Age >/= 18 years old

          4. Prior therapy with growth factor support, lenalidomide, 5-azacytidine, decitabine or
             other investigational agents is allowed if last dose was given more than 14 days prior
             to first dose of LBH 589.

          5. Previously untreated patients are eligible for this study.

          6. Patients must meet the following laboratory criteria: AST/SGOT and ALT/SGPT </= 2.5 x
             upper limit of normal (ULN) or </= 5.0 x ULN if the transaminase elevation is due to
             leukemic involvement; Serum bilirubin </= 1.5 x ULN; Serum creatinine </= 1.5 x ULN or
             24-hour creatinine clearance >/= 50 ml/min; Serum potassium >/= lower limit of normal
             (LLN); Serum phosphorous >/= LLN; Serum total calcium (corrected for serum albumin) or
             serum ionized calcium >/= LLN; Serum magnesium >/= LLN; TSH and free T4 within normal
             limits (WNL) (patients may be on thyroid hormone replacement)

          7. Baseline MUGA or ECHO must demonstrate LVEF >/= the lower limit of the institutional
             normal of 50%.

          8. ECOG Performance Status of </= 2

          9. Women of childbearing potential (WOCBP) defined as not post-menopausal for 12 months
             or no previous surgical sterilization must have a negative serum pregnancy test within
             72 hours of the first administration of oral LBH589.

         10. Male patients who agree to use a condom during sexual contact with a female of child
             bearing potential.

         11. Patients with a heart rate >/= 50 beats per minute with or without a pacemaker.

        Exclusion Criteria:

          1. Prior treatment with an HDAC inhibitor for MDS or any other malignancy.

          2. Patients currently treated with valproic acid for neurological or other conditions who
             can not be changed to another therapy.

          3. Impaired cardiac function including any one of the following: Screening ECG with QTc >
             450 msec confirmed by central laboratory prior to enrollment in study; Pts with
             congenital long QT syndrome; History of sustained ventricular tachycardia; History of
             ventricular fibrillation or torsades de pointes; Pts with myocardial infarction or
             unstable angina within 6 mo. of study entry; Congestive heart failure; Right bundle
             branch block with left anterior hemiblock (bifascicular block)

          4. Concomitant use of drugs with a risk of causing torsades de pointes. A wash-out period
             of at least 72 hours is required. Patients using medications that have a relative risk
             of prolonging the QT interval or inducing torsades de pointes if treatment cannot be
             discontinued or switched to a different medication prior to starting study drug.

          5. Concomitant use of CYP3A4 inhibitors. A wash-out period of at least 72 hours is
             required.

          6. Patients with unresolved diarrhea greater than CTCAE grade 1

          7. Patients who have undergone major surgery less than 4 weeks prior to screening visit
             or who have not recovered from side effects of such therapy.

          8. Patients who have received chemotherapy, any investigational drug or undergone major
             surgery within 3 weeks prior to starting study drug or who have not recovered from
             side effects of such therapy (CTCAE Grade 1), with the exception of nitrosoureas,
             which should be discontinued at least six weeks before enrollment.

          9. Concomitant use of any anti-cancer therapy or radiation therapy.

         10. Patients with a history of another primary malignancy within 5 years other than
             curatively treated CIS of the cervix, or basal or squamous cell carcinoma of the skin

         11. Patients with known positivity for human immunodeficiency virus (HIV) ) or hepatitis
             C.

         12. Patients with any significant history of non-compliance to medical regimens or with
             inability to grant a reliable informed consent

         13. Female patients who are pregnant or breastfeeding.

         14. Uncontrolled hypertension, history of labile hypertension, or history of poor
             compliance with an antihypertensive regimen.

         15. Impairment of GI function or GI disease that may significantly alter the absorption of
             LBH589

         16. Peripheral neuropathy greater than CTCAE grade 2