Patient case: 63-year-old female with melanoma; genetic feature: NRAS (Q61R)

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

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.

Detailed description: 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: 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

Relevance to patient case: not relevant