Panobinostat (LBH589): Acute Graft Versus Host Disease (aGVHD) Prevention

A Phase II Trial Evaluating the Use of a Histone Deacetylase Inhibitor Panobinostat for Graft Versus Host Disease (GVHD) Prevention

This study will test PANO in combination with tacrolimus/sirolimus (TAC/SIR) for acute GVHD prevention. The purpose of this study is to determine if Panobinostat (PANO) when used in combination with sirolimus and tacrolimus will help reduce the incidence of Graft-vs-host disease (GVHD).

Inclusion Criteria:

• Age ≥ 18 years or older at time of enrollment
• Signed informed consent
• Hematologic disorder requiring allogeneic hematopoietic cell transplantation
• Left ventricular ejection fraction (LVEF) ≥ 45% by multiple uptake gated acquisition (MUGA) scan or echocardiogram
• Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and diffusing lung capacity oxygenation (DLCO) adjusted ≥ 50% of predicted values on pulmonary function tests
• Transaminases (AST, ALT) < 3 times upper limit of normal (ULN) values
• Creatinine clearance calculated ≥ 50 mL/min
• Karnofsky Performance Status Score ≥ 60%.
• Human leukocyte antigen (HLA) matched 8/8 (A, B, C, DRB1) related or unrelated donor

Exclusion Criteria:

• Active infection not controlled with appropriate antimicrobial therapy
• HIV, hepatitis B (HBcAb positive but HBsAg negative with undetectable viral load are eligible), or hepatitis C infection
• Sorror's co-morbidity factors with total score > 4. Important modification to co-morbidity index calculation: DLCO adjusted will not be included in assessment of pulmonary risk, except those patients with DLCO adjusted < 50% who are excluded from the trial.
• Anti-thymocyte globulin (ATG) as part of the conditioning regimen
• Cyclophosphamide as part of the conditioning regimen or for GVHD prophylaxis
• Pregnancy
• Histone deacetylase (HDAC), DAC, HSP90 inhibitors or valproic acid for the treatment of cancer within 30 days
• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first PANO treatment
• Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: Any history of ventricular fibrillation or torsade de pointes; Bradycardia defined as heart rate (HR)< 45 bpm (Patients with pacemakers are eligible if HR ≥ 45 bpm); Screening electrocardiogram (ECG) with a QTcF > 480 msec; Right bundle branch block + left anterior hemiblock (bifascicular block); Patients with myocardial infarction or unstable angina ≤ 12 months prior to starting study drug; Other clinically significant heart disease (e.g., New York Heart Association (NYHA) class III or IV , uncontrolled hypertension) as per discretion of principal investigator and/or treating physician; 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 with the exception of drugs listed on Appendix B of study documents that are required for hematopoietic cell transplantation (HCT) patients.