High-Dose Aldesleukin and Ipilimumab in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed By Surgery
Condition: Recurrent Melanoma; Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma
MeSH terms: Melanoma
Intervention: aldesleukin; ipilimumab; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Correlative studies
Intervention MeSH terms: Aldesleukin; Antineoplastic Agents, Immunological; Ipilimumab; Interleukin-2; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well high-dose aldesleukin and ipilimumab works in treating
      patients with stage III-IV melanoma that cannot be removed by surgery. Biological therapies,
      such as aldesleukin, may stimulate or suppress the immune system in different ways and stop
      tumor cells from growing. Monoclonal antibodies, such as ipilimumab, interfere with the
      ability of tumor cells to grow and spread. Giving high-dose aldesleukin together with
      ipilimumab may work better in treating patients with melanoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willing and able to give written informed consent

          -  Histologic or cytologic diagnosis of cutaneous melanoma that is considered
             unresectable (stage III) or metastatic (stage IV); ocular and mucosal melanoma is
             excluded

          -  White blood cell (WBC) >= 2000/uL

          -  Absolute neutrophil count (ANC) >= 1000/uL

          -  Platelets >= 75 x 10^3/uL

          -  Hemoglobin >= 9 g/dL (>= 80 g/L; may be transfused)

          -  Creatinine =< 2.0 x upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN for
             patients without liver metastasis, =< 5 times for patients with liver metastases

          -  Bilirubin =< 2.0 x ULN, (except patients with Gilbert's syndrome, who must have a
             total bilirubin less than 3.0 mg/dL)

          -  No known active or chronic infection with human immunodeficiency virus (HIV),
             hepatitis B, or hepatitis C; testing is not required unless clinically suspected

          -  Performance status (Eastern Cooperative Oncology Group [ECOG] 0-1)

          -  Patients must have a life expectancy of greater than three months at the start of the
             trial

          -  Patients must have a brain magnetic resonance imaging (MRI) that is free of active
             metastases; metastases that have been treated with radiation or surgical resection,
             are stable for at least 4 weeks and do not require steroids are eligible

          -  Patients may have received treatment of completely resected early stage melanoma,
             comprising interferon, radiation treatment, or experimental vaccine therapy, and in
             the metastatic setting patient can have had treatment such as chemotherapy,
             immunotherapy (except prior treatment with ipilimumab and IL-2), and other
             experimental agent which was completed 4 weeks prior to enrollment

          -  Normal cardiac stress test for patients over 50 years of age

          -  Forced expiratory volume in 1 second (FEV1) > 65% of prediction for those patients
             with extensive pulmonary metastases or chronic pulmonary disease history

          -  Forced vital capacity (FVC) > 65% of prediction for those patients with extensive
             pulmonary metastases or chronic pulmonary disease history

          -  Women of childbearing potential (WOCBP) must be using an adequate method of
             contraception to avoid pregnancy throughout the study and for up to 26 weeks after the
             last dose of investigational product, in such a manner that the risk of pregnancy is
             minimized; in general, the decision for appropriate methods to prevent pregnancy
             should be determined by discussions between the investigator and the study subject;
             WOCBP include any female who has experienced menarche and who has not undergone
             successful surgical sterilization (hysterectomy, bilateral tubal ligation, or
             bilateral oophorectomy) or is not post-menopausal; post-menopause is defined as:

               -  Amenorrhea >= 12 consecutive months without another cause, or

               -  For women with irregular menstrual periods and taking hormone replacement therapy
                  (HRT), a documented serum follicle stimulating hormone (FSH) level >= 35 mIU/mL

               -  Women who are using oral contraceptives, other hormonal contraceptives (vaginal
                  products, skin patches, or implanted or injectable products), or mechanical
                  products such as an intrauterine device or barrier methods (diaphragm, condoms,
                  spermicides) to prevent pregnancy, or are practicing abstinence or where their
                  partner is sterile (eg, vasectomy) should be considered to be of childbearing
                  potential

               -  WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25
                  IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours
                  before the start of ipilimumab

               -  Men of fathering potential must be using an adequate method of contraception to
                  avoid conception throughout the study (and for up to 26 weeks after the last dose
                  of investigational product) in such a manner that the risk of pregnancy is
                  minimized

        Exclusion Criteria:

          -  Any other malignancy form which the patient has been disease-free for less than 5
             years, with the exception of adequately treated and cured basal or squamous cell skin
             cancer, superficial bladder cancer or carcinoma in situ of the cervix

          -  Patients with primary ocular or mucosal melanoma are excluded

          -  Patients with a history of inflammatory bowel disease, including ulcerative colitis
             and Crohn's disease, are excluded from this study, as are patients with a history of
             symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis
             [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's
             granulomatosis]); motor neuropathy considered of autoimmune origin (e.g.
             Guillain-Barre syndrome and Myasthenia Gravis)

          -  Any underlying medical or psychiatric condition, which in the opinion of the
             investigator will make the administration of ipilimumab hazardous or obscure the
             interpretation of adverse events (AEs), such as a condition associated with frequent
             diarrhea

          -  Patients with underlying heart conditions who are deemed ineligible for surgery by
             cardiology consult; patients with reversible ischemic changes on cardiac stress test

          -  Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to
             1 month before or after any dose of ipilimumab)

          -  A history of prior treatment with IL-2, ipilimumab or prior cytotoxic T-lymphocyte
             antigen 4 (CTLA4) inhibitor or agonist

          -  Concomitant therapy with any of the following: interferon, or other non-study
             immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other
             investigation therapies; or chronic use of systemic corticosteroids

          -  Women of childbearing potential (WOCBP), who:

               -  Are unwilling or unable to use an acceptable method of contraception to avoid
                  pregnancy for their entire study period and for at least 8 weeks after cessation
                  of study drug, or

               -  Have a positive pregnancy test at baseline, or

               -  Are pregnant or breastfeeding

          -  Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
             treatment of either a psychiatric or physical (eg, infectious) illness