Interleukin-21 in Treating Patients With Metastatic or Recurrent Malignant Melanoma

OBJECTIVES:

Primary

• To assess the efficacy, in terms of objective response rate, nonprogression rate, time to progression, and response duration, in patients with metastatic or recurrent malignant melanoma treated with recombinant human interleukin-21 (rIL-21).
• To assess the toxicity and safety of rIL-21 in patients with previously untreated metastatic or recurrent malignant melanoma.
• To characterize the pharmacokinetics of rIL-21.
• To characterize the effects of rIL-21 on lymphocyte cell count and soluble CD25 (sCD25) in serum as potential biomarkers for drug activity.
• To evaluate the immunogenicity of rIL-21, specifically preexisting immunogenicity to the drug and antibody induction during treatment.
• To assess melanoma antigenic markers for response and nonprogression on archival tissue from patients enrolled on the study.

Secondary

• To investigate whether rIL-21 induced sCD25 release is independent of the level of circulating sCD25.
• To investigate the effect of rIL-21 on antibody induction during treatment and preexisting immunogenicity.
• To assess lymphocyte cell-count changes over time in relation to rIL-21 therapy.

OUTLINE: This is a multicenter study.

Patients receive recombinant human interleukin-21 (rIL-21) IV on days 1-5 of weeks 1, 3 and 5. Treatment repeats every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) or partial response (PR) receive 2 courses beyond CR or PR. Patients with stable disease receive a maximum of 3 courses of rIL-21.

Previously archived tumor tissue and blood samples are collected from patients for correlative studies. Samples are analyzed for soluble CD25, rIL-21 antibodies, circulating lymphocyte counts, preexisting immonogenicity to rIL-21 for antibody induction, and expression of common melanoma tumor antigen markers via IHC.

After completion of study treatment, patients are followed at 4 weeks.

DISEASE CHARACTERISTICS:

• Histologically confirmed cutaneous malignant melanoma

• Recurrent or metastatic disease that is not curable by surgical or other means
• Clinically and/or radiologically documented disease defined as at least one site of disease unidimensionally measurable ≥ 20 mm by x-ray, physical exam, or nonspiral CT scan OR ≥ 10 mm by spiral CT scan
• Must have nonbulky metastatic disease defined as the largest measurable lesion ≤ 50 mm in maximum diameter
• Must have primary diagnosis tumor tissue or previously resected metastatic melanoma tissue available (i.e., paraffin block or unstained slides)
• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• Absolute granulocytes count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Bilirubin normal
• Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Negative pregnancy test
• Not pregnant or nursing
• Fertile patients must use effective contraception during study therapy
• No uncontrolled intercurrent illness or condition including, but not limited to, any of the following:

• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness or social situation that would limit compliance with study requirements
• No history of hemolysis or a hemolytic disorder including, but not limited to, any of the following:

• Sickle cell anemia
• Thalassemia
• Autoimmune hemolytic anemia
• No history of other malignancies within the past 5 years except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other solid tumors curatively treated with no evidence of disease
• No known HIV, hepatitis B, or hepatitis C infection
• Patients must reside within a 2-hour drive from a participating center

PRIOR CONCURRENT THERAPY:

• No previous systemic therapy for metastatic disease
• At least 3 months since prior adjuvant immunotherapy for recurrent melanoma

• No prior immunotherapy for metastatic disease
• No prior immunotherapy outside the adjuvant setting
• At least 4 weeks since prior major surgery
• At least 4 weeks since prior radiotherapy except low-dose, nonmyelosuppressive radiotherapy and recovered
• More than 4 weeks since prior and no concurrent investigational agents or anticancer therapy
• No prior chemotherapy including regional therapy
• No concurrent systemic corticosteroids (e.g., prednisone or dexamethasone)

• Concurrent topical steroids are allowed