A Phase 2 Multicenter Study of High Dose Chemotherapy With Autologous Stem Cell Transplant Followed by Maintenance Therapy With Romidepsin for the Treatment of T Cell Non-Hodgkin Lymphoma

The primary aim is to determine a preliminary estimate of the progression-free survival of
patients with T NHL who receive maintenance romidepsin at 2 years post-transplant for
patients transplanted in CR1 or PR1 with standard risk histologies.

Secondary aims include:

- Determine PFS at 2 yrs for patients transplanted in ≥CR/PR2 or for patients with high
risk histologies.

- Determine the toxicities associated with romidepsin following autologous transplantation

- Determine the probability of OS at 2 years post transplant for all patients undergoing
transplant

- Characterize the effect of romidepsin on immune recovery post HDT-ASCT

- OS and PFS 1 year after Romidespin completion

Patients who receive romidepsin after transplant will be evaluable for the primary endpoint,
and will be counted towards the accrual total. Any patient who does not receive romidepsin
after transplant, regardless of reason, will be replaced. We will also accrue a second cohort
of 8 patients who are transplanted in >CR/PR2 and for high risk histologies to be analyzed
for secondary endpoints only. This cohort will not be part of the primary endpoint and will
be analyzed for summary statistics only. Patients who receive romidepsin after transplant
will be counted towards the accrual total for Cohort 2. Any patient who does not receive
romidepsin after transplant, regardless of reason, will be replaced.

Inclusion Criteria:

- Age: Patients over age 16 who are deemed eligible for transplant by their treating
physician Disease status: CR or PR required. Remission status will be assessed at the
completion of induction chemotherapy and prior to enrollment on protocol.

Diagnosis: The following histologies will need to be confirmed at MSK or locally for
participating sites in order to be considered for HDT-ASCT and post-transplant maintenance
romidepsin:

- PTCL

- AITL

- ALCL

- EaTCL

- Hepatosplenic Gamma Delta T cell lymphoma

- Adult T-cell leukemia/lymphoma

- Primary cutaneous gamma/delta T-cell lymphoma

- Extranodal NK/T-cell lymphoma, nasal type

- Primary cutaneous anaplastic large cell lymphoma

- Subcutaneous panniculitis-like T-cell lymphoma

- Mycosis fungoides/sezary syndrome Stem cell collection: A minimum of 2 x 106 CD34+
cells must have been collected

Laboratory test results within these ranges:

- Total bilirubin <= 1.5 x ULN

- AST (SGOT) and ALT (SGPT) <= 3 x ULN

Exclusion Criteria:

- Diagnosis: progressive disease at transplant work-up

- Prior therapy: prior autologous or allogeneic transplant

- Active and uncontrolled infection at time of transplantation including active
infection with Aspergillus or other mold, or HIV infection

- Inadequate performance status/organ function defined by DLCO < 50% (adjusted for hgb),
cardiac function as defined below, KPS < 60%.

- Pregnant or breast feeding. For males and females of child-producing potential,
inability to use effective contraceptive methods during the study

- Prior therapy with romidepsin

- Central nervous system or meningeal involvement

- Any known cardiac abnormalities such as:

- Congenital long QT syndrome

- QTc interval ≥ 500 milliseconds

- Myocardial infarction within 6 months of transplantation. Subjects with a history
of myocardial infarction between 6 and 12 months prior to transplant who are
asymptomatic and have had a negative cardiac risk assessment (treadmill stress
test, nuclear medicine stress test, or stress echocardiogram) since the event may
participate

- Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV)
block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50
beats/min)

- Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV (see
Appendix 1) 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

- Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class
II to IV definitions (see Appendix 2) and/or ejection fraction <40% by MUGA scan
or <50% by echocardiogram and/or MRI

- A known history of sustained ventricular tachycardia (VT), ventricular
fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently
addressed with an automatic implantable cardioverter defibrillator (AICD)

- Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or
other causes

- Uncontrolled hypertension, defined as 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
doses of beta-blockers)

- Patients taking drugs leading to significant QT prolongation within the specified
wash out period (See Appendix 3: Medications That May Cause QTc Prolongation).

- Concomitant use of CYP3A4 inhibitors