Anti-MART-1 F5 Cells Plus ALVAC MART-1 Vaccine to Treat Advanced Melanoma
Condition: Metastatic Melanoma; Skin Cancer
MeSH terms: Melanoma; Skin Neoplasms
Intervention: autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes; ALVAC MART-1 Vaccine; aldesleukin; cyclophosphamide; fludarabine phosphate
Intervention description: ALVAC vaccine-approximately two hours prior to cell infusion, patients will receive 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 MART-1 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2 mL). This will be repeated on day 14.; ALVAC vaccine-approximately two hours prior to cell infusion, patients will receive 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 MART-1 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2 mL). This will be repeated on day 14.; Aldesleukin - 720,000 IU/kg intravenous over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses); 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
Intervention MeSH terms: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 4.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Immunotherapy; Metastatic Melanoma; Vaccination; Tumor Regression; Skin Cancer

Summary:

      Background:

        -  Melanoma antigen recognized by T-cells (MART)-1 is a protein present in melanoma cells.

        -  An experimental procedure developed for treating patients with melanoma uses the
           anti-MART-1 F5 gene and a type of virus to make special cells called anti-MART-1 F5
           cells that are designed to destroy the patient's tumor. These 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) MART-1, made from a virus that ordinarily infects canaries and is modified to
           carry a copy of the MART-1 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-MART-1 F5 cells.

      Objectives:

      -To evaluate the safety and effectiveness of anti-MART-1 F5 and the ALVAC vaccine in treating
      patients with advanced melanoma.

      Eligibility:

      -Patients 18 years of age 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
           anti-MART-1 F5.

        -  Patients receive the ALVAC vaccine, anti-MART-1 F5 cells and interleukin-2 (IL-2) (an
           approved treatment for advanced melanoma). The anti-MART-1 F5 cells are given as an
           infusion through a vein. The vaccine is given as injections just before the infusion of
           anti-MART-1 F5 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 MART-1 by immunohistochemistry (IHC) which will be reviewed by the
             Laboratory of Pathology at National Cancer Institute (NCI).

          4. Tumor infiltrating lymphocytes (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 Cooperative 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. Patients 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 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.

         14. 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 2.0 mg/dl, except in patients with
                  Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

         15. 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).

         16. Six weeks must have elapsed since prior MDX-010 therapy to allow antibody levels to
             decline.

         17. 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 or ischemic symptoms.

          8. Any patient known to have an left ventricular ejection fraction (LVEF) less than or
             equal to 45 percent.

          9. Documented LVEF of less than or equal to 45 percent tested in patients with:

               -  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.

         10. Documented forced expiratory volume in 1 second (FEV1) less than or equal to 60
             percent predicted tested in patients with:

               -  A prolonged history of cigarette smoking (20 pk/yrs of smoking).

               -  Symptoms of respiratory dysfunction.