A Pilot Study of Oncaspar® + Dexamethasone in Patients With Relapsed or Refractory T-Cell Lymphoma

This is an open-label, investigator-initiated, single-arm pilot study. Patients with
relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL) will receive Oncaspar® every
3 weeks up to a maximum of 8 courses or until disease progression or unacceptable toxicity.
They will also receive dexamethasone 40mg daily for 4 days with every cycle. They will be
restaged after 2 courses (6 weeks) and after 8 courses (24 weeks).

Both Oncaspar and dexamethasone have been used together to treat ALL and ENKTL, which is
another subtype of T cell lymphoma. The combination may provide a collaborative attack
against the cancer cell; moreover, the dexamethasone could also prevent some of the side
effects of Oncaspar; especially allergic reactions. This study will test these two drugs
together to determine if they are an effective treatment for T-Cell Lymphoma. Each drug is
commercially available to the drug market.

Inclusion Criteria:

- Patients must meet the following criteria on screening examination to be eligible to
participate in the study:

- Patients must have histologically confirmed peripheral T-cell lymphoma, with the
diagnostic specimen reviewed at one of the DFHCC hematopathology laboratories.
Eligible histologies include:

- PTCL-NOS

- Systemic T cell/null anaplastic large cell lymphoma (ALCL), regardless of Alk status

- Angioimmunoblastic T-cell lymphoma (AITL)

- Hepatosplenic (alpha-beta or gamma-delta) lymphoma (HSL)

- Enteropathy-associated T-cell lymphoma (EATL)

- Adult T-cell leukemia/lymphoma (ATLL), lymphomatous subtype

- Subcutaneous panniculitis-like T-cell lymphoma

- T-cell Prolymphocytic Leukemia (T-PLL)

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >
20 mm with conventional techniques or as > 10 mm with spiral CT scan

- Patients must have relapsed or progressed after at least 1 prior course of
anti-lymphoma therapy.

- Age 18-65 years.

- ECOG performance status <2 (see Appendix A).

- Ability to understand and the willingness to sign a written informed consent
document.

Exclusion Criteria:

- Patients who exhibit any of the following conditions at screening will not be
eligible for admission into the study.

- Patients with cutaneous disease only are not eligible.

- Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 3 weeks earlier to
grade 1 or below (unless approved by the Study Chair).

- Patients may not be receiving any other study agents at the time of first treatment.

- History of treatment with an asparaginase agent.

- Patients with a history of alcohol abuse, or patients unwilling or unable to remain
completely abstinent of alcohol during the study period.

- Hepatitis B or C seropositivity (except for hepatitis B with negative surface antigen
and hepatitis B viral load).

- Total bilirubin > institutional upper limit of normal (ULN), unless due to hemolysis
or Gilbert's disease).

- AST/ALT ≥ 3 x ULN.

- History of pancreatitis, or amylase > ULN or lipase > ULN.

- History of thromboembolic disease.

- Grade 2 or above neuropathy.

- Diabetes mellitus, unless it is type II diabetes adequately controlled with
anti-diabetic agents (A1c < 7).

- History of CNS hemorrhage or thrombosis. Patients with a history of CNS lymphomatous
involvement are eligible only if their CNS disease is in remission at the time of
study entry.

- Uncontrolled intercurrent illness including, but not limited to uncontrolled active
infection, symptomatic congestive heart failure (New York Hospital Association (NYHA)
class II-IV, resulting in at least slight limitation of activity), unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements.

- Inability to provide informed consent

- Pregnancy or lactation.

- Individuals with a history of a different malignancy are ineligible except for the
following circumstances. Individuals with a history of other malignancies are
eligible if they have been disease-free for at least 3 years and are deemed by the
investigator to be at low risk for recurrence of that malignancy. Individuals with
the following cancers are eligible if diagnosed and treated within the past 3 years:
cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.

- HIV-positive individuals on combination antiretroviral therapy are ineligible.