Trial of Neoadjuvant Ipilimumab Followed by Melphalan Via Isolated Limb Infusion for Patients With Unresectable In-transit Extremity Melanoma

Exclusion Criteria

• •1. Cardiac disease: Congestive heart failure greater than class II NYHA. Patients must not have unstable angina (angina symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
• •2. Autoimmune disease: History of or current active autoimmune diseases, \[e.g. including but not limited to inflammatory bowel diseases \[IBD\], rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barre syndrome). Vitiligo and adequately controlled endocrine deficiencies such as hypothyroidism are not exclusionary.\]
• •3. Prior allogeneic stem cell transplantation.
• •4. Patients who have had a history of acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.
• •5. History of or current immunodeficiency disease \[e.g. splenectomy or splenic irradiation\].
• •6. Psychiatric conditions or diminished capacity that could compromise the giving of informed consent, or interfere with study compliance; 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 AEs, such as a condition associated with frequent diarrhea.
• •7. Concomitant therapy with any of the following: IL 2, interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses). However, during the course of the study, use of corticosteroids is allowed if used for treating irAEs, adrenal insufficiencies, or if administered at doses of prednisone greater than or equal to 7.5mg daily or equivalent.
• •8. Women of childbearing potential (WOCBP), defined above in Section 5.1, who:
• •1. are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 26 weeks after cessation of study drug, or
• •2. have a positive pregnancy test at baseline, or
• •3. are pregnant or breastfeeding.
• •9. Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 26 weeks after ipilimumab is stopped.
• •Sexually active WOCBP must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Before study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during study participation and the potential risk factors for an unintentional pregnancy. All WOCBP MUST have a negative pregnancy test before first receiving ipilimumab. If the pregnancy test is positive, the patient must not receive ipilimumab and must not be enrolled in the study.
• •10. Known brain metastasis.
• •11. Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
• •12. Active clinically serious infection greater than CTCAE Grade 2.
• •13. Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
• •14. Pulmonary hemorrhage/bleeding event greater than CTCAE Grade 2 within 4 weeks of study entry.
• •15. Any other hemorrhage/bleeding event greater than CTCAE Grade 3 within 4 weeks of study entry.
• •16. Evidence or history of bleeding diathesis or coagulopathy.
• •17. Antineoplastic therapy, radiotherapy, or any other investigational drug within 30 days prior to first study drug administration.
• •18. Current treatment, or treatment in the previous 24 months, for another non-melanoma malignancy, with the exception of adequately treated basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the cervix.
• •19. Unable to return at the regular required intervals for reassessment, or study drug administration.
• •20. Patients with known heparin induced thrombocytopenia.