Inclusion Criteria:

• Patients must have histologically or cytologically confirmed (at original diagnosis or subsequent recurrence or progression) lymphoma, chronic lymphocytic lymphoma (CLL) or solid tumor; patients with lymphoma or CLL must have radiologically or clinically evaluable disease, and be refractory to standard therapy as defined by relapse within 6 months of last treatment (see note below); patients with solid tumors must have radiologically or clinically evaluable disease that is metastatic, unresectable, progressive, or recurrent, and for which standard curative measures do not exist or are no longer effective
  • Patients with a liver mass, raised alpha-fetoprotein level (≥ 500 ng/mL) and positive serology for hepatitis, consistent with a diagnosis of hepatocellular carcinoma will be eligible without the need for pathologic confirmation of the diagnosis
  • Patients with prostate cancer, renal cell cancer, neuroendocrine tumors, lung cancer, colorectal cancers, soft tissue sarcomas, glioma and thyroid cancer are excluded in the normal and mild cohorts due to a lack of efficacy in these tumor types in phase 2 studies; patients with breast, pancreatic, bladder, head and neck cancers, as well as melanoma and other malignancies are eligible
  • Note: patients with prostate cancer, renal cell cancer, lung cancer, colorectal cancers, soft tissue sarcomas, glioma and thyroid cancer are allowed to enroll in the moderate and severe cohorts provided the patients:
    • Sign a separate consent form which outlines the lack of efficacy observed in prior studies
    • Are consented to the study by a protocol-specified designee who is not their longitudinal oncologist; patients with neuroendocrine tumors are still excluded from the moderate and severe cohorts
  • Note: as romidepsin is approved for patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) or cutaneous T cell lymphoma (CTCL), these patients would be eligible WITHOUT the requirement of having 'relapsed within 6 months of last treatment'
• Life expectancy of > 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
• Hemoglobin ≥ 9 g/dL (transfusions and/or erythropoietin are permitted)
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
• Platelets ≥ 100 x 10^9/L (or platelet count ≥ 30 × 10^9 cells/L in patients with lymphoma or CLL if bone marrow disease involvement is documented)
• Creatinine ≤ twice upper limit institutional normal
• Patients with abnormal liver function will be eligible and will be grouped according to the criteria below
  • Group A (normal hepatic function)
    • Bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) ≤ ULN
  • Group B (mild hepatic dysfunction)
    • B1: bilirubin ≤ ULN and AST > ULN
    • B2: bilirubin > ULN but ≤ 1.5 x ULN and any AST
  • Group C (moderate hepatic dysfunction)
    • Bilirubin > 1.5 x ULN to ≤ 3 x ULN and any AST
  • Group D (severe hepatic dysfunction)
    • Bilirubin > 3 x ULN and up to investigators discretion and any AST
  • Patients with active hemolysis should be excluded; no distinction will be made between liver dysfunction due to metastases and liver dysfunction due to other causes; registration laboratory investigations will be used to assign a patient to a hepatic function group; liver function tests should be repeated within 24 hours prior to starting initial therapy and may result in the patients' group assignment being altered if different to registration test results
• Patients with brain metastases who require corticosteroids or non-enzyme inducing anticonvulsants must be on a stable dose of corticosteroids and seizure free for 1 month prior to enrollment; patients with known brain metastases should have completed brain irradiation (whole brain or gamma knife) more than 4 weeks before starting the protocol; patients on enzyme inducing anticonvulsants are not eligible; note that patients should have had their steroids tapered to low dose (i.e. < 1.5 mg of dexamethasone/day) due to the potential for higher dexamethasone doses to induce cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
• Patients with biliary obstruction for which a stent has been placed are eligible, provided the shunt has been in place for at least 10 days prior to the first dose of romidepsin and the liver function has stabilized; two measurements at least 2 days apart that put the patient in the same hepatic dysfunction stratum will be accepted as evidence of stable hepatic function; there should be no evidence of biliary sepsis
• Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or PK of romidepsin will be determined following review of their case by the site principal investigator
  • Patients treated with any of the medications prohibited must discontinue their use at least 7 days prior to the first dose of romidepsin; certain other agents that interact with the CYP3A4 system may be used with caution
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; note: since romidepsin binds to the estrogen receptor, the effectiveness of estrogen containing contraceptives may be reduced
• Human immunodeficiency virus (HIV)-positive patients who are not receiving: agents with the potential for PK interactions with romidepsin or hepatotoxic antiretrovirals (nucleoside reverse-transcriptase inhibitors [NRTIs]: abacavir, didanosine, emtricitabine, lamivudine, stavudine, and zidovudine), dual protease inhibitor (PI)-based regimens except low-dose boosting with ritonavir, atazanavir, indinavir, maraviroc, and nevirapine may be eligible; additionally, the HIV-positive patients should have a cluster of differentiation (CD)4 count > 250/mm^3; if the specific cause of hepatic dysfunction is unknown, the patient should be worked up for other viral causes of hepatitis and their eligibility determined after consultation with the principal investigator
• Patients who have received prior romidepsin use are eligible
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had (prior to entering the study): major surgery is not permitted within 4 weeks of romidepsin administration; anti-cancer therapy including chemotherapy, radiotherapy, hormonal (with the exception of hormones for thyroid conditions), and other investigational agents will not be allowed within 14 days or five (5) half-lives (whichever is longer) prior to the first dose of romidepsin (6 weeks for nitrosoureas or mitomycin C); additionally, participants must have recovered to less than grade 2 clinically significant adverse effect(s)/toxicity(ies) of the previous therapy, with the exception of alopecia, unless approved by the principal investigator; biologics or immunotherapy will not be allowed within 28 days prior to, or during, romidepsin administration
• Patients with prostate cancer, renal cell cancer, neuroendocrine tumors, lung cancer, colorectal cancers, soft tissue sarcomas, glioma, and thyroid cancer are excluded in the normal and mild cohorts due to a lack of efficacy in these tumor types in phase 2 studies; patients with prostate cancer, renal cell cancer, lung cancer, colorectal cancers, soft tissue sarcomas, glioma and thyroid cancer are allowed to enroll in the moderate and severe cohorts only; patients with neuroendocrine tumors are still excluded from the moderate and severe cohorts
• Patients may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to romidepsin, including cyclic tetrapeptide compounds
• Concurrent medications associated with a risk of corrected QT interval (QTc) prolongation and/or Torsades de Pointes are not allowed within 2 weeks of initiation of study treatment; those medications as reported but lacking substantial evidence for causing QTc prolongation and Torsades de Pointes will be allowed, although if an alternative medication can be substituted, that would be preferable
• Thiazolidinedione agents such as rosiglitazone and pioglitazone are not permitted
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with current evidence of significant cardiovascular disease (New York Heart Association class III or IV cardiac disease), symptomatic congestive heart failure, dilated/hypertrophic or restrictive cardiomyopathy, myocardial infarction (within the past 6 months), unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of medications for rate control for atrial fibrillation is allowed such as calcium channel blockers and beta-blockers, if stable medication for at least last month prior to initiation of romidepsin treatment and medication not listed as causing Torsades de Pointes), or evidence of acute ischemia on electrocardiogram (ECG); marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval > 450 msec*; long QT syndrome; the required use of concomitant medication that may cause Torsades de Pointes or may cause a significant prolongation of the QTc
  • Note: due to difficulties assessing QTc in patients with heart block, they may be eligible if deemed safe by a cardiologist
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with this drug
• Warfarin is not permitted