Study of 5-azacitidine in Combination With Vorinostat in Patients With Relapsed or Refractory Diffuse Large b Cell Lymphoma (DLBCL)

Inclusion Criteria:

* Patients must have histologically confirmed diffuse large B cell lymphoma, relapsed after or resistant to prior systemic therapy.
* Subjects must have measurable disease on cross sectional imaging that is at least 1.5 cm in diameter.
* Patients should have relapsed following or be deemed ineligible for autologous stem cell transplantation. There is no limit to number of prior therapies.
* Age \> = 18 years.
* ECOG performance status \< = 2.
* Patients must have normal organ and marrow function as defined below:

  * ANC \> = 1,000/uL
  * platelets \> = 75,000//uL
  * total bilirubin \< = 2 X upper limit of normal
  * AST(SGOT)/ALT(SGPT) \< = 2.5 X upper limit of normal
  * Serum creatinine \< = 1.5 X upper limit of normal (ULN)
* Women of childbearing potential must have a negative serum pregnancy test prior to treatment
* The effects of these investigational agents on the developing human fetus at the recommended therapeutic doses are unknown. For this reason, women of child-bearing 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. A woman who becomes pregnant while participating in the study must withdraw from the study immediately.
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Prior allogeneic transplant
* Patients may not be receiving any other investigational agents.
* Patients may not have previously received anti-lymphoma therapy with an HDAC inhibitor (.e.g. Depsipeptide, MS-275, LAQ-824, PXD-101, and valproic acid). Patients who have received an HDAC inhibitor for another indication such as epilepsy may enroll after a 30-day washout period
* Patients with known active CNS lymphoma. Subjects with previous CNS lymphoma that have been treated with chemotherapy, radiotherapy or surgery who have remained asymptomatic for 90 days (3 months) and demonstrate, no CNS lymphoma, as shown by lumbar puncture, CT scan or MRI, are eligible..
* Patients with known hypersensitivity to azacytidine, vorinostat or mannitol.
* Patients with a currently active second malignancy.
* Uncontrolled 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.
* QTc interval \> 0.470. Consider discontinuation of medications that prolong QTc interval to eliminate this exclusion if medically appropriate.
* Pregnant and lactating women are excluded from the study because the risks to an unborn fetus or potential risks in nursing infants are unknown.