Azacitidine and Romidepsin in Treating Patients with Relapsed or Refractory Lymphoid Malignancies

Inclusion Criteria

• Phase I: Patients must have histologically confirmed relapsed or refractory non-Hodgkin lymphoma or Hodgkin lymphoma (World Health Organization [WHO] criteria), with no accepted curative options
• Phase II: Patients with untreated, relapsed or refractory T-cell lymphoma, including patients with central nervous system (CNS) involvement or lymphomatous meningitis are allowed on study
• Exploratory Cohort: Patients with histologically confirmed relapsed or refractory germinal center (GC)-derived B-Cell lymphoma (diffuse large B-cell [DLBCL] and follicular lymphoma [FL]) defined by the WHO and Hans criteria with no accepted curative options
• There is no upper limit for the number of prior therapies; patients may have relapsed after prior autologous or allogeneic stem cell transplant
• Evaluable disease in the Phase I, and measurable disease for the Phase II
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Absolute neutrophil count >= 1,000/dL
• Platelets >= 75,000 total (>= 50,000 if bone marrow involvement)
• Bilirubin =< 1.5 X institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.0 X institutional upper limit of normal
• Serum creatinine within normal institutional limits OR creatinine clearance >= 50 mL/min/for patients with creatinine levels above institutional normal
• Negative urine or serum pregnancy test for females of childbearing potential
• All females of childbearing potential must use an effective barrier method of contraception (either an intrauterine contraceptive device [IUDC] or double barrier method using condoms or a diaphragm plus spermicide) during the treatment period and for at least 1 month thereafter; male subjects should use a barrier method of contraception during the treatment period and for at least 3 months thereafter; female subjects should avoid the use of estrogen-containing contraceptives, since romidepsin may reduce the effectiveness of estrogen-containing contraceptives
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Prior therapy * Exposure to chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier * Systemic steroids that have not been stabilized (>= 5 days) to the equivalent of =< 10 mg/day prednisone prior to the start of the study drugs * No other concurrent investigational agents are allowed
• History of allergic reactions to oral 5-azacitidine or romidepsin
• Uncontrolled 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
• Pregnant women
• Nursing women
• Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix); patients whose lymphoma has transformed from a less aggressive histology remain eligible
• Patients known to be human immunodeficiency virus (HIV)-positive
• Patients with active hepatitis A, hepatitis B, or hepatitis C infection
• Concomitant use of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors
• Any known cardiac abnormalities such as: * Congenital long QT syndrome * Corrected QT (QTc) interval >= 500 milliseconds * Patients taking drugs leading to significant QT prolongation * Myocardial infarction within 6 months of course 1 day 1 (C1D1); (subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment [treadmill stress test, nuclear medicine stress test, or stress echocardiogram] since the event, may participate) * Other significant electrocardiogram (ECG) abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min) * Symptomatic coronary artery disease (CAD), e.g., angina Canadian class II-IV; in any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present * An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of >= 2 mm, measured from isoelectric line to the ST segment); if in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present * Congestive heart failure (CHF) that meets New York Heart Association (NYHA) class II to IV definitions and/or ejection fraction < 40% by multigated acquisition (MUGA) scan or < 50% by echocardiogram and/or MRI; * A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD) * Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes * Uncontrolled hypertension, i.e., blood pressure (BP) of >= 160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria; or * Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)