Inclusion Criteria

- INCLUSION CRITERIA:

Based on the Inclusion Criteria outlined below, patients will accrue to one of the cohorts
of the trial.

Cohort- chemotherapy regimens allowed. Cohort Status

Cohort 1

Cutaneous T-cell Lymphoma (mycosis fungoides or Sezary syndrome)-2 or fewer. Closed to
accrual

Cohort 2

Peripheral T-cell Lymphoma, unspecified, or Anaplastic large cell lymphoma (T and null
cell) Primary Cutaneous Type -2 or fewer. Open and accruing

Cohort 3

Cutaneous T-cell Lymphomas or Peripheral T-cell Lymphoma-More than 2. Closed to accrual

Cohort 4

Other Mature T cell Lymphomas-Any number. Open and accruing

Cohort 5

Cutaneous T-cell Lymphoma (mycosis fungoides or Sezary syndrome)-2 or fewer-Cohort 5 is a
replicate cohort, identical to #1

Cohort 6

Peripheral T-cell Lymphoma, unspecified, or Anaplastic large cell lymphoma (T and null
cell) Primary Cutaneous Type-More than 2. Patients with PTCL in cohort 3 migrated to this
cohort

Cohort 7

Cutaneous T-cell Lymphoma (mycosis fungoides or Sezary syndrome) Prior vorinostat
required-Any number

Patients with cutaneous T-cell lymphoma [CTCL (mycosis fungoides or Sezary syndrome) stage
IB to IVB are eligible. Patients with stage IB and IIA should be refractory to,
intolerant to, or have reached a six-month or longer response plateau on at least two
prior therapies from the following list: PUVA, UVB, EBT, photophoresis, interferon,
systemic cytotoxic chemotherapy, topical nitrogen mustard, or topical carmustine (BCNU).
One qualifying prior treatment must have been topical nitrogen mustard, topical carmustine
or a phototherapy (UVB, PUVA or EBT). Topical steroids, systemic retinoids or biologicals
do not qualify. Patients with stage IB or IIA who are not candidates for topical nitrogen
mustard, topical carmustine or phototherapy (UVB, PUVA or EBT) are eligible for
enrollment. Patients may not have received more than two systemic cytotoxic chemotherapy
regimens. Steroids, retinoids, and biologic agents, will not be considered as systemic
cytotoxic chemotherapy. Radiolabeled monoclonal antibody therapy is considered equivalent
to a systemic cytotoxic chemotherapy regimen and must be counted toward the two prior
systemic cytotoxic regimens. Patients with stage IIB-IVB who have had no more than 2
prior systemic cytotoxic chemotherapeutic regimens are eligible. There is no restriction
regarding number of prior topical therapies, skin irradiation, or non-cytotoxic systemic
therapies (i.e. PUVA, retinoids or biologic, with the exception of radiolabeled monoclonal
antibody therapy) in this patient group. After 24 patients were enrolled in this arm, the
arm was closed, and a replicate arm constituted of this same patient population was opened
(Cohort 5).

Patients with peripheral T-cell lymphoma (PTCL), unspecified, or anaplastic large cell
lymphoma, T and null cell, primary cutaneous type, as defined by the REAL/WHO
classification (16-18), who have experienced disease progression after receiving prior
standard treatment and who have had no more than 2 prior systemic cytotoxic
chemotherapeutic regimens are eligible.

Patients with cutaneous T cell lymphoma (Mycosis fungoides or S zary Syndrome) or
peripheral T cell lymphoma as defined above who have received more than 2 prior systemic
therapies and who have experienced disease progression will be included in a third and
independent arm. This arm of the protocol was closed to accrual for CTCL with Amendment H.

Patients with mature T cell lymphomas not included above will be enrolled in a fourth arm.
These include but are not exclusively limited to: Enteropathy-type T cell lymphoma;
Hepatosplenic T-cell lymphoma; Subcutaneous panniculitis-like T cell lymphoma;
Angioimmunoblastic T-cell lymphoma; Anaplastic large cell lymphoma. Patients must have
experienced disease progression after receiving prior standard treatment. There will be no
limit on the number of prior regimens. Primitive T cell neoplasms and T cell leukemias
will not be enrolled.

Patients with peripheral T-cell lymphoma, unspecified, or anaplastic large cell lymphoma,
T and null cell, primary cutaneous type, as defined by the REAL/WHO classification
(16-18), who have experienced disease progression after receiving prior standard treatment
and who have had more than 2 prior systemic cytotoxic chemotherapeutic regimens are
eligible for enrollment to a sixth arm of the trial.

Patients with cutaneous T cell lymphoma (Mycosis fungoides or S zary Syndrome) or
peripheral T cell lymphoma as defined in #1 who have received any number of prior systemic
therapies and who have previously been treated with vorinostat will be included in a third
and independent arm. Patients can be enrolled in this arm if they received prior
vorinostat and experienced disease progression, subsequent relapse, or had to discontinue
to agent due to toxicity.

Disease that is measurable by radiographic imaging, assessing skin lesions, or by
quantitating Sezary cell count.

Patients must:

be age greater than or equal to 18 years

have a performance status of ECOG 0-2

have no serious or intercurrent illness and have a life expectancy of greater than 12
weeks

give written informed consent

female patients of childbearing potential must have a negative pregnancy test within 4
weeks and must use effective contraception

sexually active males must use effective contraception

Laboratory values (performed less than or equal to 14 days prior to registration):

absolute neutrophil count greater than or equal to 1000/microliter, platelets greater than
or equal to l00,000/microliter, bilirubin (total and direct) less than or equal to 1.5x
upper limit of normal, and AST less than or equal to 3x upper limit of normal, unless
impairment is due to organ involvement by lymphoma, creatinine less than or equal to 1.5x
upper limit of normal, or documented creatinine clearance of greater than or equal to
60mL/min

Cardiac studies (performed within 4 weeks of registration):

Ejection fraction of greater than 50% by Echocardiogram or Cardiac MRI, or greater than or
equal to 45% by MUGA Scan.

A stable dose (greater than 1 month) of corticosteroids administered for symptom
management will not preclude enrollment. Tapering will be initiated following
administration of depsipeptide.

EXCLUSION CRITERIA:

Patients with unconfirmed diagnosis, or with B-cell lymphomas will be excluded.

Prior or concurrent malignancies that have not been curatively treated.

Known CNS lymphoma.

Chemotherapy within 4 weeks, 6 weeks for nitrosoureas or mitomycin C.

Biologics, Immunotherapy within 2 weeks.

HIV seropositivity.

Pregnant or breast-feeding patients.

Major surgery within 21 days.

Uncontrolled infection or uncontrolled medical illness.

Patients having received prior HDAC inhibitor therapy for T cell lymphoma will be excluded
except for patients eligible to enroll in cohort 7.

Patients with the following cardiac risk factors will be excluded from the study:

Patients with known cardiac abnormalities such as:

Congenital long QT syndrome

QTc interval greater than 480 milliseconds

Patients who have had a myocardial infarction within 12 months of study entry.

Patients who have active coronary artery disease as, e.g. angina as defined by Canadian
Class II-IV

Patients with an ECG recorded at screening showing evidence of cardiac ischemia (ST
depression of greater than or equal to 2 mm).

Any patient in whom coronary artery disease is suspected should be referred for a
cardiology consultation and if active myocardial ischemia is demonstrated the patient
should be excluded. If a noninvasive imaging study is equivocal, it may be necessary to
proceed to coronary angiography.

Patients with congestive heart failure that meets NYHA Class II to IV definitions and/or
ejection fraction less than 45% by MUGA scan or less than 50% by echocardiogram and/or
MRI.

Patients with a history of sustained VT, VF, Torsade de Pointes, or cardiac arrest unless
currently addressed with an automatic implantable cardioverter defibrillator (AICD).
Patients with a history of arrhythmia should have Holter monitoring and evaluation by
cardiology.

Patients with dilated, hypertrophic, or restrictive cardiomyopathy from prior treatment or
other causes (in doubt, see ejection fraction criteria above). Patients with left
ventricular hypertrophy should be discussed with the Principal Investigator or Study
Chairman.

Patients with uncontrolled hypertension, i.e., SBP greater than or equal to 160 mm Hg or
DBP greater than or equal to 95 mm Hg.

Patients with cardiac arrhythmia requiring anti-arrhythmic medication other than beta
blocker or calcium channel blocker. Patients in whom digitalis cannot be discontinued are
excluded from study.

Patients with Mobitz II second degree heart block who do not have a pacemaker. Patients
with first degree or Mobitz I second degree heart block, bradyarrhythmias or sick sinus
syndrome require Holter monitoring and evaluation by cardiology.

Patients with other cardiac disease may be excluded at the discretion of the PI following
consultation with cardiology.