LBH589 in Refractory Myelodysplastic Syndromes (MDS)
Condition: Myelodysplastic Syndromes (MDS)
MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome
Intervention: Panobinostat
Intervention description: Panobinostat(20 mg or 30 mg PO) will be administered three times a week on Monday, Wednesday and Friday. Treatment will be given over 21 days followed by a 7 day rest period and repeated every 28 days. Patients will be assessed for toxicity on an ongoing basis and disease assessment will be determined every 2 treatment cycles (8 weeks). Patients will be allowed to continue on treatment for a maximum of eight four week treatment cycles. Treatment will be discontinued if there is evidence of disease progression, unacceptable toxicity and/or at the discretion of the investigator.
Intervention MeSH terms: Panobinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myelodysplastic Syndromes (MDS); Refractory; LBH589

Summary:

      This will be a single arm Phase II study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytological documented diagnosis of myelodysplastic syndrome (MDS).

          -  Male or female patients aged >= 18 years old.

          -  MDS patients who have failed hypomethylating (azacitidine or decitabine) therapy.

          -  Patients with 5q-cytogenic abnormalities must also have progressed on or been
             intolerant to lenalidomide.

          -  Patients with up to and including 30% blasts (FAB RAEB-T) will be eligible to enroll.

          -  CMML with >= 5% blasts will be eligible to enroll.

          -  ECOG PS 0, 1 or 2.

          -  Laboratory values must be as follows:

        Bilirubin <= 1.5 mg/dL AST/SGOT <= 2.5 x ULN ALT/SGPT Creatinine <= 2.0 mg/dL or 24-hour
        Creatinine Clearance >= 50 ml/min Albumin >= 3 g/dL Potassium >= lower limit normal (LLN)
        Phosphorous >= LLN Calcium >= LLN Magnesium >= LLN

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 7 days prior to start of treatment.

          -  Life expectancy >= 12 weeks.

        Exclusion Criteria:

          -  Prior treatment with an HDAC inhibitor.

          -  Prior intensive chemotherapy or high dose ara-C (>= 1 gm/m2)

          -  More than one prior single agent chemotherapy regimen. Prior hydroxyurea for
             cytoreduction will be permitted however.

          -  Impaired cardiac function

          -  Active CNS disease, including leptomeningeal metastases.

          -  Unresolved diarrhea > CTCAE grade 1.

          -  Chemotherapy, investigational drug therapy, major surgery < 4 weeks prior to starting
             study drug or patients that have not recovered from side effects of previous therapy.

          -  Patient is < 5 years free of another primary malignancy except if the other primary
             malignancy is not currently clinically significant or requiring active intervention,
             or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in
             situ. Existence of any other malignant disease is not allowed.

          -  Women who are pregnant or breast feeding or women of childbearing potential (WOCBP)
             not willing to use a double barrier method of contraception during the study and 3
             months after the end of treatment. One of these methods of contraception must be a
             barrier method.

          -  Male patients whose sexual partners are WOCBP not using a double method of
             contraception during the study and 3 months after the end of treatment. One of these
             methods must be a condom.

          -  Patients with gastrointestinal (GI) tract disease, causing the inability to take oral
             medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation,
             prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease
             (e.g., Crohn's disease, ulcerative colitis).

          -  Other concurrent severe, uncontrolled systemic fungal, bacterial, viral or other
             infection or intercurrent illness, including but not limited to ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Patients with uncontrolled coagulopathy.

          -  Abnormal thyroid function (TSH or free T4) detected at screening. Patients with known
             hypothyroidism who are stable on thyroid replacement are eligible.