Gemcitabine and Pemetrexed Disodium in Treating Patients With Advanced Mycosis Fungoides or Sézary Syndrome

OBJECTIVES:

1. Determine the safety and tolerability of gemcitabine hydrochloride and pemetrexed
disodium in patients with advanced mycosis fungoides or Sézary syndrome. (Phase I)

2. Determine the maximum tolerated dose of gemcitabine hydrochloride when administered with
pemetrexed disodium in these patients. (Phase I)

OUTLINE: This is a phase I, dose-escalation study of gemcitabine hydrochloride. Originally,
this was designed to be followed by a phase II portion to determine the efficacy in this
population. Unfortunately, due to a lack of funding, the phase II portion was never
conducted.

During Phase I: Patients receive pemetrexed disodium IV over 10 minutes and gemcitabine
hydrochloride IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease
progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which ≥ 2 of 6
patients experience dose-limiting toxicity.

DISEASE CHARACTERISTICS:

- Histologically confirmed* mycosis fungoides or Sézary syndrome

- Stage IB-IVB disease NOTE: *Pathology report must read diagnostic or consistent
with mycosis fungoides/Sézary syndrome

- Failed ≥ 1 prior systemic treatment

- Measurable disease

- At least 1 indicator lesion must be designated prior to study entry

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy ≥ 6 months

- Creatinine ≤ 2.0 mg/dL

- Creatinine clearance ≥ 45 mL/min

- Bilirubin ≤ 2.2 mg/dL

- AST and ALT ≤ 2 times upper limit of normal

- WBC ≥ 3,000/mm³

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- No acute infection requiring systemic treatment

- No history of severe hypersensitivity reaction to the study drugs or to any other
ingredient used in their formulation

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 4 weeks since prior topical therapy, systemic chemotherapy, or biological
therapy

- No acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs) for 2
days before and for 2 days after pemetrexed disodium infusion (5 days before and for 2
days after pemetrexed disodium infusion for patients taking NSAIDs with a long
half-life [e.g., naproxen, refocoxib, or celecoxib])

- No concurrent topical agents except emollients

- No other concurrent topical or systemic anticancer therapies

- No other concurrent investigational agents