Anti-gp100 Cells Plus ALVAC gp100 Vaccine to Treat Advanced Melanoma
Condition: Metastatic Melanoma; Skin Cancer
MeSH terms: Melanoma; Skin Neoplasms
Intervention: cyclophosphamide; fludarabine phosphate; Aldesleukin; ALVAC gp100 Vaccine; anti-gp100:154-162 Tcell receptor (TCR) peripheral blood lymphocyte (PBL)
Intervention description: 60 mg/kg day x 2 days intravenous in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg day x 2 days over 1 hour; 25 mg/m^2 day intravenous piggy back over 30 minutes for 5 days; 720,000 IU/kg intravenously over 15 minutes every 8 hours (+/- 1 hour) for up to 5 days.; 0.5 ml containing a target dose of 10^7 CCID50 (with a range of approximately 10^6,4 to 10^7,9/mL) of the gp100 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2mL); 3 x 10^11 anti-gp100:154-162 TCR engineered PBL by intravenous infusion. A minimum of approximately 5 x 10^8 cells will be given.
Intervention MeSH terms: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic Melanoma; Immunotherapy; Vaccination; Tumor Regression; Skin Cancer

Summary:

      Background:

        -  gp100 is a protein that is often found in melanoma tumors.

        -  An experimental procedure developed for treating patients with melanoma uses anti-gp100
           cells designed to destroy their tumors. The anti-gp100 cells are created in the
           laboratory using the patient's own tumor cells or blood cells.

        -  The treatment procedure also uses a vaccine called plaque purified canarypox vector
           (ALVAC) gp100, made from a virus that ordinarily infects canaries and is modified to
           carry a copy of the gp100 gene. The virus cannot reproduce in mammals, so it cannot
           cause disease in humans. When the vaccine is injected into a patient, it stimulates
           cells in the immune system that may increase the efficiency of the anti gp 100 cells.

      Objectives:

      -To evaluate the safety and effectiveness of anti-gp100 cells and the ALVAC gp100 vaccine in
      treating patients with advanced melanoma.

      Eligibility:

      -Patients with metastatic melanoma for whom standard treatments have not been effective.

      Design:

        -  Patients undergo scans, x-rays and other tests and leukapheresis to obtain white cells
           for laboratory treatment.

        -  Patients have 7 days of chemotherapy to prepare the immune system for receiving the
           gp100 cells.

        -  Patients receive the ALVAC vaccine, anti-gp100 cells and interleukin-2 (IL-2) (an
           approved treatment for advanced melanoma). The anti gp100 cells are given as an infusion
           through a vein. The vaccine is given as injections just before the infusion of gp100
           cells and again 2 weeks later. IL-2 is given as a 15-minute infusion every 8 hours for
           up to 5 days after the cell infusion for a maximum of 15 doses.

        -  After hospital discharge, patients return to the clinic for periodic follow-up with a
           physical examination, review of treatment side effects, laboratory tests and scans every
           1 to 6 months.
    

Eligibility criteria:

        -INCLUSION CRITERIA:

          1. Metastatic melanoma with measurable disease.

          2. Previously received high dose interleukin-2 (IL-2) and have been either non-responders
             (progressive disease) or have recurred.

          3. Positive for gp100 by immunohistochemistry (IHC) which will be reviewed by the
             Laboratory of Pathology at National Cancer Institute (NCI).

          4. Tumor infiltrating lymphocyte (TIL) cells not available for treatment on other Surgery
             Branch protocols.

          5. Greater than or equal to 18 years of age.

          6. Willing to sign a durable power of attorney.

          7. Able to understand and sign the Informed Consent Document.

          8. Clinical performance status of Eastern Oncology Oncology Group (ECOG) 0 or 1.

          9. Life expectancy of greater than three months.

         10. Patients of both genders must be willing to practice birth control for four months
             after receiving the preparative regimen.

         11. Must be human leukocyte antigens (HLA-A) 0201 positive.

         12. 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.

         13. Hematology:

               -  Absolute neutrophil count greater than 1000/mm^3.

               -  White blood cell (WBC) (greater than 3000/mm^3).

               -  Platelet count greater than 100,000/mm^3.

               -  Hemoglobin greater than 8.0 g/dl.

         14. Chemistry

               -  Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than
                  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 2.0 mg/dl, except in patients with
                  Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

         15. Women of child-bearing potential must have a negative pregnancy test because of the
             potentially dangerous effects of the preparative chemotherapy on the fetus.

         16. More than four weeks must have elapsed since any prior systemic therapy at the time
             the patient receives the preparative regimen, and patients' toxicities must have
             recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).

         17. Six weeks must have elapsed since prior MDX-010 therapy to allow antibody levels to
             decline, and patients who have previously received MDX-010 or ticilimumab must have a
             normal colonoscopy with normal colonic biopsies.

        EXCLUSION CRITERIA:

          1. Women of child-bearing potential who are pregnant or breastfeeding because of the
             potentially dangerous effects of the preparative chemotherapy on the fetus or infant.

          2. 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.

          3. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency
             Disease).

          4. Ongoing 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).

          5. Systemic steroid therapy.

          6. History of severe immediate hypersensitivity reaction to any of the agents used in
             this study.

          7. History of coronary revascularization.

          8. Documented left ventricular ejection fraction (LVEF) of less than 45 percent in
             patients with:

               -  Clinically significant atrial and/or ventricular arrhythmias including but not
                  limited to: atrial fibrillation, ventricular tachycardia, 2 degree or 3 degree
                  heart block.

               -  Age greater than or equal to 60 years old.

          9. Documented forced expiratory volume in 1 second (FEV1) less than or equal to 60
             percent predicted for patients with:

               -  A prolonged history of cigarette smoking (greater than 20 pack/year within the
                  past 2 years).

               -  Symptoms of respiratory distress.