Romidepsin, Ifosfamide, Carboplatin, and Etoposide in Treating Participants With Relapsed or Refractory Peripheral T-Cell Lymphoma

PRIMARY OBJECTIVES:

I. To assess the safety profile of romidepsin given before and after ifosfamide, carboplatin,
etoposide (ICE) chemotherapy for patients with relapsed or refractory peripheral T-cell
lymphoma (PTCL).

II. To determine the maximum tolerated dose (MTD), if reached, of romidepsin administered in
combination with ICE chemotherapy in patients with relapsed or refractory PTCL.

SECONDARY OBJECTIVES:

I. To determine the overall response rate (ORR) and complete response (CR) rate in patients
with relapsed or refractory PTCL.

OUTLINE: This is a dose-escalation study of romidepsin.

Participants receive romidepsin intravenously (IV) over 4 hours on days 1 and 4, ifosfamide
IV over 24 hours on day 1, carboplatin IV over 1 hour on day 1, and etoposide IV over 2 hours
on day 1-3. Treatment repeats every 14 days for up to 6 courses in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, participants are followed up within 2-4 weeks.

Inclusion Criteria:

- Relapsed or refractory T cell lymphoma (TCL) status including diagnoses of peripheral
TCL-not otherwise specified (NOS), angioimmunoblastic TCL, anaplastic large cell
lymphoma, hepatosplenic TCL, enteropathy-associated TCL, or mycosis
fungoides(MF)/cutaneous TCL with transformation to systemic TCL

- Patients must have received at least one chemotherapy regimen which contained
doxorubicin

- At least one 1.5 cm bidimensional measurable lesion or bone marrow positivity of TCL

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Absolute neutrophil count (ANC) >= 1000 cells/mm3

- Platelets >= 80,000 cells/mm3 if baseline bone marrow negative for TCL involvement and
platelets >= 20,000 cells/mm3 if baseline bone marrow positive for TCL involvement

- Bilirubin =< 2 x upper limits of normal (ULN) (Gilbert's =< 3 x upper limit of normal
[ULN])

- Creatinine =< 1.5 x ULN

- Alanine aminotransferase (ALT) and aminotransferase (AST) =< 3 x ULN

- Negative pregnancy test for females of childbearing potential within 7 days prior to
start of treatment. Patients of reproductive potential must follow accepted birth
control methods which include hormonal contraceptive, intra-uterine device, diaphragm
with spermicide, condom with spermicide, or abstinence during treatment and for 3
months after completion of treatment

- Voluntarily signed Institutional Review Board (IRB) approved informed consent document
(ICD) before performance of any study-related procedure not part of normal medical
care, with the understanding that consent may be withdrawn by the subject at any time
without prejudice to future medical care

Exclusion Criteria:

- History of another malignancy not in remission for at least 2 years (yrs) (except
non-melanoma skin cancer, stage 0 melanoma, localized prostate cancer, cervical cancer
in situ)

- Known active Central Nervous System (CNS) lymphoma

- Ejection fraction (EF) of < 40%, myocardial infarction (MI) within past 3 months,
uncontrolled angina, severe uncontrolled ventricular arrthymias, or electrocardiogram
(ECG) evidence of acute ischemia

- Grade 3 infection within 2 weeks of first dose romidepsin plus ICE

- Pregnant or lactating

- Receipt of another investigational drug within 14 days of enrollment

- Patients with previous hypersensitivity reactions to the study drugs and components
(ex: podophyllum and povidone)