Phase II Study of Aldesleukin (IL-2) Following the Administration of Zanolimumab (Anti-CD4mAb) in Metastatic Melanoma and Metastatic Renal Cancer
Condition: Metastatic Melanoma; Metastatic Renal Cancer
MeSH terms: Melanoma; Kidney Neoplasms; Carcinoma, Renal Cell
Intervention: Zanolimumab; Aldesleukin
Intervention description: 14 mg/kg as an intravenous infusion weekly (+/- 3 days) for 9 weeks.; 720,000 IU/kg every 8 hours for a maximum of 15 doses.
Intervention MeSH terms: Aldesleukin; Zanolimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic Melanoma; Metastatic Kidney Cancer; Clinical Performance; Tumor Regression; Toxicity

Summary:

      Background:

        -  Aldesleukin (IL-2) is a drug that can help to shrink tumors in some patients with
           metastatic renal cancer and metastatic melanoma. It is possible that removing certain
           white blood cells (known as CD4 cells) before IL-2 treatment may improve the treatment
           effects.

        -  Zanolimumab is an antibody that works by destroying CD4 cells in the blood. Researchers
           are interested in determining whether zanolimumab can improve the results of IL-2
           treatment if it is given before, during, and after IL-2 treatment. In addition, further
           research with zanolimumab may provide more information on how IL-2 treatment causes
           tumors to stop growing or shrink.

      Objectives:

      - To evaluate the effectiveness of IL-2 treatment in conjunction with zanolimumab in
      individuals with metastatic cancer.

      Eligibility:

      - Individuals at least 18 years of age who have been diagnosed with metastatic melanoma or
      metastatic kidney cancer.

      Design:

        -  Eligible participants will be screened with a full physical examination and medical
           history, imaging studies, and blood samples, including leukapheresis, to remove a sample
           of white blood cells for testing purposes. Participants may also have a colonoscopy and
           biopsies if they have received previous treatments that have been known to cause colon
           damage.

        -  Participants will be treated with zanolimumab and IL-2 treatment for 9 weeks.

        -  Zanolimumab will be given on an outpatient basis during weeks 1 through 4, 6, 8, and 9.
           In weeks 5 and 7, participants will receive zanolimumab as an inpatient in addition to
           IL-2 therapy.

        -  Inpatient IL-2 treatment will be given during weeks 5 and 7. Up to 15 doses of IL-2
           treatment will be given over a maximum of 5 days, followed by inpatient recovery time.

        -  During week 5, participants will have tumor imaging studies prior to receiving
           zanolimumab and IL-2 treatment.

        -  About 2 weeks after the treatment period, participants will return to the clinical
           center for a 2-day evaluation with a physical examination, imaging studies, and blood
           samples.

        -  Participants whose tumors have responded to treatment will be offered up to two
           additional courses of treatment, starting 6 to 8 weeks after the last IL-2 dose.
           Subsequent courses will be given exactly as described above in the initial course of
           treatment. Participants whose tumors do not respond to treatment will have follow-up
           evaluations as required by the study researchers.
    

Eligibility criteria:

        -  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