Phase II Study of Aldesleukin (IL-2) Following the Administration of Zanolimumab (Anti-CD4mAb) in Metastatic Melanoma and Metastatic Renal Cancer

Study start date: June 1, 2010

* INCLUSION CRITERIA: * Measurable metastatic melanoma or metastatic renal cancer. Metastatic cancer diagnosis will be confirmed by the Laboratory of Pathology at the National Cancer Institute (NCI). * Patients must never have received high dose aldesleukin. * Greater than or equal to 18 years of age. * Willing to sign a durable power of attorney * Able to understand and sign the Informed Consent Document * Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1. * Life expectancy of greater than three months. * Patients of both genders must be willing to practice birth control for four months after receiving treatment. * Serology: * Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.) * Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen negative. * Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the therapy on the fetus. * Hematology: * Absolute neutrophil count greater than 1000/mm\^3 without the support of filgrastim. * White blood cell (WBC) (greater than 3000/mm\^3). * Platelet count greater than 100,000/mm\^3. * Hemoglobin greater than 8.0 g/dl. * Chemistry: * Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 2.5 times the upper limit of normal. * Serum creatinine less than or equal to 1.6 mg/dl. * Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl. * More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives zanolimumab, and patient's toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo). * Six weeks must have elapsed since prior anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) antibody therapy to allow antibody levels to decline, and patients who have previously received anti-CTLA4 antibody and have documented gastrointestinal (GI) toxicity must have a normal colonoscopy with normal colonic biopsies. EXCLUSION CRITERIA: * Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the therapy on the fetus or infant. * Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease. * Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease). * Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities). * Concurrent systemic steroid therapy * History of severe immediate hypersensitivity reaction to any of the agents used in this study. History of coronary revascularization or ischemic symptoms * Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45%. * Documented LVEF of less than or equal to 45% tested in patients with: * History of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block * Age greater than or equal to 60 years old. * Documented forced expiratory volume 1 (FEV1) less than or equal to 60% predicted tested in patients with: * A prolonged history of cigarette smoking (20 pack year of smoking within the past 2 years). * Symptoms of respiratory dysfunction