Panobinostat Plus Ifosfamide, Carboplatin, and Etoposide (ICE) Compared With ICE For Relapsed Hodgkin Lymphoma

Inclusion Criteria

• Histologically confirmed classical Hodgkin lymphoma (nodular sclerosis, mixed cellularity, or lymphocyte-rich classical HL).
• Patients must have failed (relapsed or refractory) front-line standard anthracycline-containing regimen, such as ABVD, Stanford V, or BEACOPP.
• Bidimensionally measurable disease with at least 1 lesion >/= 2.0 cm in a single dimension
• Acceptable hematologic status: Hemoglobin >/= 9.0 g/dL, Absolute neutrophil count >/= 1500 cells/mm3, Platelet count >/= 100,000 cells/mm3
• Normal serum K+, Mg+, PO4, and total Ca++ (pre-treatment abnormal values may be therapeutically corrected before starting therapy and must be documented as normal or if abnormal values persist must be documented as clinically insignificant). Albumin should be >/= 3
• Pre-study World Health Organization (WHO) performance status of 0, 1, or 2
• Age >/= 16 years
• Voluntary signed Institutional Review Board (IRB) approved consent informed before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Patients of reproductive potential (female of child bearing potential has not been postmenopausal for at least 12 consecutive months or not surgically sterile; male of child bearing potential has not been surgically sterile)must follow accepted birth control methods (e.g. barrier method) during treatment.
• Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
• Baseline Multiple Gated Acquisition (MUGA) or ECHO must demonstrate left ventricular ejection fraction (LVEF) >/= 50%.

Exclusion Criteria

• Lymphocyte predominant histology
• More than one prior chemotherapy regimens.
• Prior therapy with other HDAC inhibitors, including valproic acid
• Prior therapy with heat shock protein (HSP)-90 inhibitors
• Prior stem cell transplant
• Abnormal liver function: Bilirubin > 2.0 mg/dL (26 µmol/L), Alkaline phosphatase > 2 x upper limits of normal (ULN), aspartate aminotransferase AST (SGOT) and/or alanine aminotransferase ALT > 2 x ULN
• Serum creatinine >1.5 mg/dl
• Presence of Central Nervous System (CNS) involvement with Hodgkin lymphoma
• Presence of Human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS).
• Another primary malignancy (other than squamous cell and basal cell carcinoma of the skin, in situ carcinoma of the cervix, or treated prostate cancer with a stable Prostate Specific Antigen PSA) for which the patient has not been disease free for at least 3 years.
• Serious nonmalignant disease (e.g., congestive heart failure, hydronephrosis); active uncontrolled bacterial, viral, or fungal infections; or other conditions which would compromise protocol objectives in the opinion of the investigator
• Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:History or presence of sustained ventricular tachyarrhythmia, Any history of ventricular fibrillation or torsade de pointes, Bradycardia defined as HR /= 50 bpm, Screening ECG with a corrected QT interval (QTc) > 450 msec, Right bundle branch block + left anterior hemiblock (bifascicular block), Patients with myocardial infarction or unstable angina Common Terminology Criteria for Adverse Events Version 4 (CTCAE V.4) grade 2
• 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.
• Patients who have received either immunotherapy within 30% of marrow-bearing bone within </= 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies.
• Patients who have undergone major surgery </= 4 weeks prior to starting study drug or who