Phase I Study of Romidepsin, Gemcitabine, Oxaliplatin, and Dexamethasone in Patients With Relapsed/Refractory Aggressive Lymphomas

Inclusion Criteria:

- Able to understand and voluntarily sign an informed consent form

- Age ≥ 18 at time of informed consent

- Diagnosis of one of the following:

- relapsed/refractory peripheral T-cell lymphoma of any subtype including mycosis
fungoides and Sézary syndrome of advanced stage (IIB-IVB)

**for the expansion cohort:patients must have biopsy-proven T-cell lymphoma and
measurable disease.

- relapsed/refractory DLBCL (up to 6 DLBCL patients are allowed in the
dose-escalation portion of the study)

- relapsed/refractory HL

Note: extracorporeal photopheresis is NOT considered a systemic therapy for this study.

- Transplant eligible (as determined by referring physician) patients who have failed
one prior salvage therapy or transplant ineligible (as determined by referring
physician) patients who have failed one prior therapy

- ECOG performance status of ≤ 2

- Laboratory test results within the following ranges:

- Absolute neutrophil count ≥ 1500/mm³

- Platelet count ≥ 100,000/mm³

- Total bilirubin ≤ 1.5 x ULN

- AST (SGOT) and ALT (SGPT) ≤ 3 x ULN

- Creatinine < 2 mg/dL

- Potassium ≥ 3.3 mmol/L or at/above the lower limit of normal for the performing
laboratory

- Magnesium ≥ 1.4 mg/dL or at/above the lower limit of normal for the performing
laboratory.

- Negative serum pregnancy test for women of childbearing potential

- Washout time of at least 4 weeks for prior biological, chemotherapeutic, or
radiotherapy

Exclusion Criteria:

- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would - in the opinion of the investigator - prevent the subject from signing the
informed consent form

- Pregnant or lactating women

- Any medical condition or laboratory abnormalities, which - in the opinion of the
investigator - places the subject at unacceptable risk, or confounds the ability to
interpret data if he/she were to participate in the study

- Positive CSF cytology during staging, symptomatic leptomeningeal involvement, or
parenchymal involvement of brain or spinal cord

- Prior allogeneic hematopoietic cell transplant

- Prior solid organ transplant

- Cirrhotic liver disease from any cause

- Known HIV infection

- Impaired cardiac function or clinically significant cardiac disease including any of
the following:

- Congenital long QT syndrome

- Screening ECG with QTc interval ≥ 500 milliseconds

- Myocardial infarction (MI) or unstable angina ≤ 6 months of C1D1; however,
subjects with a history of MI between 6 and 12 months who are asymptomatic and
have had a negative cardiac risk assessment (treadmill stress test, nuclear
medicine stress test, or stress echocardiogram) since the event would be eligible

- 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

- Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV)
block type II, 3rd degree AV block, or bradycardia (defined here as ventricular
rate < 50 bpm); right bundle-branch block + left anterior hemi-block (bifasicular
block)

- Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class
II to IV definitions (see Appendix 9) and/or ejection fraction <40% by MUGA scan
or <50% by echocardiogram and/or MRI History or presence of sustained ventricular
tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac
arrest

- 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

- Any cardiac arrhythmia requiring an anti-arrhythmic medication, excluding stable
(i.e., at least 30 days from screening) doses of beta-blockers

- Concomitant use of drugs that may cause significant QT prolongation and/or torsades de
pointes that cannot be discontinued or switched to a different medication prior to
treatment

- Concomitant use of CYP3A4 inhibitors or inducers unless able to stop medication(s)
prior to starting study treatment

- Patients who are unwilling to stop the use of herbal remedies while receiving study
treatment

- Unable to accept blood product transfusions

- Men whose sexual partners are women of childbearing potential not using a double
method of contraception during the study and 3 months after the end of treatment. One
of these methods must be a condom

- Concurrent malignancy requiring active therapy *Patients with localized prostate
cancer having undergone surgery or radiation (field confined to ≤ 30% of
marrow-bearing bone) at least 30 days prior to study treatment are eligible