Romidepsin Plus Oral 5-Azacitidine in Relapsed/Refractory Lymphoid Malignancies

Subjects will receive oral 5-azacitidine and romidepsin, administered as follows: oral
5-azacitidine from Days 1-14 (Dose cohorts -1 to 5) or Days 1-21 (Dose cohort 6); and
romidepsin administered intravenously on Days 8 (Dose cohorts 1-4) of a 28 day cycle, and Day
22 (Dose cohorts 5 and 6) of a 35 day cycle. Cohorts of 3 patients will be enrolled
sequentially as outlined in the dose escalation scheme. Once the MTD is reached the Phase II
part of the protocol will be initiated in patients with T-Cell Lymphoma.

Inclusion Criteria:

- Phase I: Histologically confirmed relapsed or refractory non-Hodgkin lymphoma or
Hodgkin lymphoma (WHO criteria), with no accepted curative options.

- Phase II: Relapsed or refractory T-cell lymphoma, including patients with central
nervous system (CNS) involvement or lymphomatous meningitis are allowed on study.

- Relapsed or refractory disease following frontline chemotherapy. 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.

- Age > or = 18 years.

- ECOG performance status < or = 2.

- Patients must have adequate organ and marrow function.

- Negative urine or serum pregnancy test for females of childbearing potential.

- All females of childbearing potential must use an effective barrier method of
contraception 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.

- 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). If there is a history of prior malignancy, the patient must be
disease-free for ≥ 3 years.

- Patients known to be Human Immunodeficiency Virus (HIV)-positive.

- Patients with active hepatitis A, hepatitis B, or hepatitis C infection.

- Concomitant use of CYP3A4 inhibitors.

- Any known cardiac abnormalities.