RATIONALE: Biological therapies, such as interleukin-12 and interleukin-2, use different ways to stimulate the immune system and stop cancer cells from growing. Combining more than one biological therapy may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining interleukin-12 with interleukin-2 in treating patients who have mycosis fungoides.

OBJECTIVES:

• Determine the response rate (complete and partial) in patients with mycosis fungoides treated with interleukin-12 (IL-12).
• Determine the frequency of refractory disease in patients treated with this drug.
• Determine the toxic effects of this drug in these patients.
• Determine the feasibility and dose-limiting toxic effects (DLT) of interleukin-2 (IL-2) when administered with IL-12 in patients who have not shown disease progression after 12 weeks of IL-12 and in those who have shown disease progression after 12 weeks of IL-12.
• Determine the maximum tolerated dose and recommended dose of IL-2 when administered with IL-12 in these patients.
• Determine immune and cytokine response over time in patients treated with this regimen.
• Determine the frequency of improved clinical response in patients treated with this regimen.
• Determine the biologic correlates of response, including levels of interferon gamma production, natural killer cell activity, infiltration of skin lesions by CD8-positive cells, lymphocyte IL-12 receptor expression, signal transducers and activators of transcription protein levels and IL-12 signal transduction, and induction of apoptosis in tumor cells in the skin of patients treated with this regimen.

OUTLINE: This is an open-label, multicenter, dose-escalation study of interleukin-2 (IL-2).

Patients receive interleukin-12 (IL-12) subcutaneously (SC) twice weekly for 24 weeks.

Disease is assessed at 13 weeks. Patients who do not have progressive disease also receive IL-2 SC 3 consecutive days a week during weeks 13-24. Patients with progressive disease at week 13 receive IL-2 SC at a fixed dose during weeks 13-24.

Patients with responding disease after week 24 may continue to receive IL-2 and IL-12 for another 12 weeks.

Cohorts of 3-6 patients receive escalating doses of IL-2 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The recommended dose (RD) is the dose preceding the MTD. Additional patients are treated at the RD.

Patients are followed at 6 months.

PROJECTED ACCRUAL: A total of 18-46 patients will be accrued for this study within 28 months.

• Biological: aldesleukin
• Biological: recombinant interleukin-12

DISEASE CHARACTERISTICS:

• Histologically confirmed mycosis fungoides

  • Stage Ib-IV
• At least 5% of total blood mononuclear cells must be CD8-positive lymphocytes
• No CNS disease

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 6 months

Hematopoietic

• WBC ≥ 3,000/mm^3 but ≤ 40,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 10 g/dL (transfusion or epoetin alfa allowed)

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2 times ULN

Renal

• Creatinine ≤ 1.5 times ULN
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• EKG normal
• No known cardiac and peripheral vascular disease
• No cardiac arrhythmias requiring medical treatment

Pulmonary

• Chest x-ray normal

Immunologic

• No history of or clinically significant autoimmune disease (e.g., rheumatoid arthritis), autoimmune hemolytic anemia, or positive Coombs' test
• No HTLV-I or HTLV-II-associated disease
• HIV negative
• Antinuclear antibody negative
• Rheumatoid factor negative
• No serious concurrent infection requiring IV antibiotics

Gastrointestinal

• No clinically significant gastrointestinal bleeding
• No uncontrolled peptic ulcer disease
• No history of inflammatory bowel disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of peripheral neuropathy
• No other major illness that would substantially increase the patient's risk

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior interferon allowed
• Prior denileukin diftitox allowed
• No prior interleukin (IL)-2 or IL-12
• No prior anti-T-cell monoclonal antibody therapy
• No other concurrent biologic therapy

Chemotherapy

• Prior topical imidazole mustard or carmustine allowed
• Prior bexarotene allowed
• Prior oral methotrexate allowed
• At least 3 weeks since prior topical chemotherapy

• At least 8 weeks since prior treatment with any single chemotherapeutic agent (12 weeks for multiple chemotherapeutic agents)

  • Treatment must not have included steroids
• No prior systemic chemotherapy
• No prior fludarabine, pentostatin, or cladribine
• No concurrent systemic chemotherapy

Endocrine therapy

• At least 3 weeks since prior topical or systemic steroids more potent than 1% hydrocortisone
• No concurrent systemic corticosteroids
• No concurrent low-potency steroid creams

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• At least 3 weeks since prior psoralen-ultraviolet-light (PUVA) or ultraviolet B (UVB)
• At least 3 weeks since prior retinoids
• At least 3 weeks since prior investigational drugs
• Prior photopheresis allowed
• No other concurrent investigational therapy