A Study of Panobinostat (LBH589) as Second-Line Therapy in Patients With Chronic Graft-Versus-Host Disease

Inclusion Criteria: 1. Chronic GvHD following allogeneic HSCT of any source (bone marrow, peripheral blood, or cord blood stem cells), from any donor type (related, unrelated, or mismatched) and with any type of malignancy. Chronic GvHD will be defined according to NIH Consensus Criteria. 2. Patients must have had inadequate response to treatment with steroids and calcineurin inhibitors. Patients must have been treated with an initial dose of at least 1 mg/kg/day of methylprednisolone (MP) or equivalent in combination with tacrolimus or cyclosporine and must fulfill the definition of steroid refractoriness or resistance. Steroid refractoriness or resistance will be defined as: 1. Lack of any response after 1 month of treatment with MP, including 15 days of at least 0.5 mg/kg/day. 2. Worsening of existing GvHD or new organ involvement at any time following one week of initiation of MP at 1 mg/kg/day. 3. Reflare or worsening of GvHD at any time during steroid taper. 4. Patients should not have received any drug or treatment for chronic GvHD other than steroids and calcineurin inhibitors (i.e., cyclosporine or tacrolimus). 3. Patient must not have evidence of primary disease relapse. 4. An ECOG (Eastern Cooperative Oncology Group) performance status of ≤2 5. Baseline MUGA or ECHO must demonstrate left ventricular ejection fraction (LVEF) ≥40%. 6. No uncontrolled arrhythmias or symptoms of heart disease. 7. FEV1, FVC, and DLCO ≥40%. 8. Laboratory values as follows: * white blood cell ≥2500/mm³; * absolute neutrophil count (ANC) ≥1,000/mm³; * hemoglobin ≥9.5 g%; * platelets ≥50,000/mm³; * total bilirubin \<3 x upper limits of normal; * aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 × the institutional upper limit of normal (ULN); * creatinine \<1.5 × ULN or creatinine clearance ≥ 50 ml/min; * serum potassium ≥ LLN; * serum sodium ≥ LLN; * serum calcium WNL; * serum phosphorus WNL; * serum magnesium WNL; 9. Patients with elevated alkaline phosphatase due to bone metastasis may be enrolled. 10. TSH and free T4 within normal limits (clinically euthyroid patients are permitted to receive thyroid supplements to treat underlying hypothyroidism). 11. Age ≥ 18 years, male or female. 12. Ability to understand and willingness to sign a written informed consent document. Exclusion Criteria: 1. Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer. 2. Patients who will need valproic acid for any medical condition during the study or ≤5 days prior to first panobinostat treatment. 3. Use of prior immunosuppressants other than steroids and calcineurin inhibitors(i.e. cyclosporine or tacrolimus). 4. Chronic active hepatitis or cirrhosis. 5. Impaired cardiac function including any of the following: * Patients with congenital long QT syndrome; * Patients with history or presence of sustained ventricular tachyarrhythmias; * Patients with any history of ventricular fibrillation or Torsades de Pointes; * Patients with bradycardia defined as HR \<50 bpm. Patients with pacemakers are eligible if HR ≥50 bpm. * Patients with myocardial infarction or unstable angina ≤6 months prior to starting study drug; * Right bundle branch block plus left anterior hemiblock (bifasicular block); * Screening ECG with QTc \>450 msec; * Congestive heart failure (CHF) \> New York Heart Association (NYHA) Class II (see Appendix D). 6. Concomitant use of drugs with a risk of causing Torsades de Pointes (see Appendix A). 7. Other concurrent severe and/or uncontrolled medical conditions. 8. Any condition that impairs patient's ability to swallow whole pills or gastrointestinal (GI) tract disease that involves an inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV)