This study will assess the safety and efficacy of Panobinostat as a single agent in the treatment of Primary Myelofibrosis, Post-Polycythemia Vera and Post-Essential Thrombocythemia. There will be two cohorts - patients with JAK2 mutation and patients without JAK2 mutation.
1. Diagnosis of myelofibrosis, either PMF, post-PV or post-ET MF with IPSS score of 2 (intermediate risk) or 3 (high risk) plus at least one of the following: Symptomatic spenomegaly (≥10cm BCM) Hemoglobin < 10 or red cell transfusion dependent. (The presence of a JAK2 V617F mutation is not required for study entry) 2. Patients must meet the following laboratory criteria:
- Patients can be either JAK2 V617F mutated or wild type
- Serum potassium, magnesium, phosphorous, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution Note: Potassium, magnesium, phosphorous, sodium, and/or calcium supplements maybe given to correct values that are < LLN. Post correction values must not be deemed to be a clinically significant abnormality prior to patients being dosed.
- Creatinine < 1.5 X ULN or Calculated CrCl ≥ 50 mL/min (MDRD Formula)
- AST and ALT ≤ 2.5 x ULN
- Serum total bilirubin ≤ 1.5 x ULN 3. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 4. Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
1. Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
2. Previous treatment with JAK2 inhibitors
3. Any patient who has previously received radiation therapy to ≥ 30% of the bone marrow
4. Impaired cardiac function or clinically significant cardiac diseases
5. Patient with unresolved diarrhea ≥ grade 2
6. Patients using medications that have a relative risk of prolonging the QT interval or inducing Torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug
7. Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of surgery
8. Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential must have a negative serum pregnancy test at screening and at baseline.
9. Male patients whose sexual partners are WOCBP not using effective birth control
10. Patients with a prior malignancy with in the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
11. Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required Other protocol-defined inclusion/exclusion criteria may apply -
Last updated: 11/15/2012
NCT ID: NCT00931762