interleukin-21 in treating patients with metastatic or recurrent malignant melanoma

Conditions: Melanoma (Skin)

Summary: rationale: interleukin-21 may stimulate white blood cells, including natural killer cells, to kill melanoma cells. purpose: this phase ii trial is studying the side effects and how well interleukin-21 works 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.

Eligibility criteria:
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

Keywords: recurrent melanoma stage iv melanoma