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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase II Study of Interleukin-21 (IL-21) in Patients With Metastatic or Recurrent Malignant Melanoma

Conditions
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Melanoma (Skin)

Intervention / Treatment
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* Biological: recombinant human interleukin-21
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Recombinant human interleukin-21<br> | Biological: recombinant human interleukin-21<br>* Patients enrolled in Part A will receive treatment daily x 5 on weeks 1, 3, and 5 of an 8 week cycle. Patients enrolled in Part B will receive treatment daily x 5 on weeks 1, and 3 of a 6 week cycle<br>Other: immunohistochemistry staining method<br>* Cycle 1 Day 1 and Cycle 1 Day 29<br>Other: laboratory biomarker analysis<br>* slides will be blocked for 15 minutes in 20% normal goat serum and then incubated in primary antibody<br>Other: pharmacological study<br>* Starting dose of 50μg/kg/day as an IV push<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumor response as assessed by RECIST |  | after completion of treatment | 
| Overall response rate (complete and partial) |  | after completion of study | 
| Stable disease rate |  | after completion of study | 
| Progressive disease rate |  | after completion of study | 
| Median time to progression |  | after completion of study | 
| Response duration (median and range) |  | after completion of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent melanoma, stage IV melanoma