Addition of Ipilimumab (MDX-010) To Isolated Limb Infusion (ILI) With Standard Melphalan and Dactinomycin In The Treatment of Advanced Unresectable Melanoma of The Extremity
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Ipilimumab, Melphalan and Dactinomycin
Intervention description: Isolated limb infusion ((ILI) with Melphalan and Dactinomycin- MSKCC operating room. Ipilimumab- IV administration in outpatient chemotherapy clinic. Induction therapy with Ipilimumab will start 1-3 weeks after ILI in the standard dose of 10mg/kg every 3 weeks for a total of 4 doses. Patients will then receive chronic therapy every 3 months. Patients will be followed every 3 months for 2 years.
Intervention MeSH terms: Dactinomycin; Ipilimumab; Melphalan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: skin; DACTINOMYCIN; MDX-010 (Ipilimumab); MELPHALAN; Isolated Limb Infusion; 10-101

Summary:

      The purpose of this study is to see the effect of adding a systemic study drug, Ipilimumab,
      to two standard chemotherapy drugs, Melphalan and Dactinomycin. The study drug Ipilimumab is
      an antibody to a normal protein found in the body, CTLA-4. This protein normally allows the
      immune system (the body's natural defense system that helps fight infections) uses to quiet
      an immune response. The study drug works by blocking this protein and allowing the immune
      system to become more active. This study will investigate the effects, of combining ILI
      (using two standard drugs to treat melanoma, Melphalan and Dactinomycin), with the study
      drug, Ipilimumab on advanced Melanoma cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willing and able to give written informed consent.

          -  Histologic diagnosis of melanoma with in transit metastasis Stage IIIB, IIIC, or IV

          -  Required values for initial laboratory tests:

          -  WBC ≥ 2000/uL

          -  ANC ≥ 1000/uL

          -  Platelets ≥ 50 x 103/uL

          -  Hemoglobin ≥ 8 g/dL

          -  Creatinine ≤ 3.0 x ULN

          -  AST/ALT ≤ 2.5 x ULN

          -  Bilirubin ≤ 3.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total
             bilirubin less than 3.0 mg/dL)

          -  No active or chronic infection with HIV, Hepatitis B, or Hepatitis C.

          -  Karnofsky performance status ≥60

          -  Men and women, ≥ 18 years of age. Women of childbearing potential (WOCBP) must be
             using an adequate method of contraception to avoid pregnancy throughout the study and
             for up to 8 weeks after the last dose of investigational product, in such a manner
             that the risk of pregnancy is minimized. 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 HCG) within 72 hours before the start of ipilimumab.

        Exclusion Criteria:

          -  Any other malignancy form which the patient has been disease-free for less than 2
             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.

          -  Autoimmune disease: Patients with a history of inflammatory bowel 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).

          -  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.

          -  Patients with underlying heart conditions who are deemed ineligible for surgery by
             cardiology consult

          -  Any history of prior treatment with ipilimumab or prior CD137 agonist or CTLA-4
             inhibitor or agonist.

          -  Concomitant therapy with any of the following: IL-2, interferon, or other non-study
             immunotherapy regimens; 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.

          -  Persons of reproductive potential must agree to use an adequate method of
             contraception throughout treatment and for at least 8 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.