Anti-MART-1 F5 Lymphocytes to Treat High-Risk Melanoma Patients
Condition: Melanoma
MeSH terms: Melanoma
Intervention: ALVAC-MART-1 vaccine; MART-1:26-35(27L) peptide vaccine; Aldesleukin; autologous anti-MART-1 F5 T-cell receptor gene-engineered peripheral blood lymphocytes; incomplete Freund's adjuvant
Intervention description: Given subcutaneously; Given subcutaneously; Given subcutaneously; Given intravenously (IV); Given subcutaneously
Intervention MeSH terms: Aldesleukin; Vaccines; Freund's Adjuvant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MART-1 Peptide; Melanoma; Adjuvant Therapy; Gene Therapy; T Cell Persistence

Summary:

      Background:

        -  Melanoma antigen recognized by T cells (MART-1) is a gene that is present in melanoma
           cells.

        -  This study tests an experimental treatment that uses the patient's own lymphocytes (type
           of white blood cell), which are specially selected and genetically modified with a gene
           called anti-MART-1 transduced cells (F5) to target and destroy their tumor. Some of the
           cells are given as an infusion and others are given as a vaccine.

        -  The anti-MART-1 F5 cells are currently being studied in other patients in combination
           with chemotherapy and IL-2 (aldesleukin) therapy.

      Objectives:

      -To determine if the anti-MART-1 F5 treatment can improve the immune system's ability to
      shrink tumors and to prevent melanoma from recurring.

      Eligibility:

        -  Patients 18 years of age and older whose melanoma has been removed and are currently
           disease-free, but who are at risk for recurrence.

        -  Patients who do not have ocular or mucosal melanoma.

        -  Patients with tissue type human leukocyte antigens (HLA-A)*0201).

      Design:

        -  Workup: Patients have scans, x-rays, laboratory tests, other tests as needed and
           leukapheresis, a procedure for collecting white cells to modify in the laboratory and
           later reinfuse into the patient.

        -  Patients are assigned to one of four study groups:

             -  Group 1 receives anti-MART-1 F5 cells by 30-minute infusion through a vein on day
                0.

             -  Group 2 receives anti-MART-1 F5 cells on day 0 followed by injections of MART-1
                vaccine, which contains MART-1 and an oil-based liquid called Montanide ISA-51 VG.
                The vaccine is repeated on day 30.

             -  Group 3 receives anti-MART-1 F5 cells on day 0 followed by injections of low-dose
                IL-2 for 5 days (days 0-4).

             -  Group 4 receives anti-MART-1 F5 cells on day 0 followed by MART-1 vaccine and
                low-dose IL-2 for 5 days. The vaccine is repeated on day 30.

        -  Recovery: Patients are monitored closely and given medicines to prevent or treat any
           side effects of therapy.

        -  Leukapheresis: Patients undergo leukapheresis at 1 and 3 months after therapy to collect
           cells to examine the effects of the treatment on the immune system.

        -  Follow-up: Patients return to National Institutes of Health (NIH) 35 days after
           completing treatment and then at 3 months and every 6 months thereafter for evaluation
           with a physical examination, review of side effects, laboratory tests and scans. They
           have blood tests at 3, 6 and 12 months after treatment and then once a year after that.
           A biopsy may be requested after treatment ends to examine the effects of treatment on
           the immune system. All patients return to NIH for a physical examination once a year for
           5 years and then complete a follow-up questionnaire for another 10 years.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Primary melanomas with lesions that are ulcerated and greater than or equal to
                  2.0 mm, or any lesions that are greater than or equal to 4.0 mm in thickness, or
                  greater than or equal to 1 positive lymph node, or local recurrence, or resected
                  metastatic disease, within 6 months of surgical resection will be considered.
                  Patients must be clinically disease free at the time of protocol entry as
                  documented by radiologic studies within 6 weeks of patient entry. Patients must
                  have pathologic confirmation of cutaneous melanoma, with slides reviewed at
                  National Institutes of Health (NIH) (Department of Anatomic Pathology), and if
                  the diagnosis is not confirmed, the patient will be excluded from the study.

               2. Human leukocyte antigens (HLA-A) 0201 positive.

               3. Age greater than or equal to18 years.

               4. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.

               5. Able to understand and sign the Informed Consent Document.

               6. Patients of both genders must be willing to practice effective birth control
                  during this trial because the potential for teratogenic effects are unknown.
                  Effective birth control requires use of an effective method from the following
                  list: Abstinence, Intrauterine device (IUD); Hormonal (Birth control pills,
                  injections, implants); Tubal ligation; Cervical cap; or Partner's vasectomy

               7. Patients may have had prior adjuvant treatment with immunotherapy, including
                  interferon, as long as 3 weeks have elapsed since prior systemic therapy.

               8. Serology:

                    1. 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.)

                    2. Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen
                       negative (The experimental treatment being evaluated in this protocol
                       depends upon an intact immune system and these conditions may have possible
                       immune system effects).

               9. Hematology:

                    1. Absolute neutrophil count greater than 1000/mm^3 without the support of
                       filgrastim.

                    2. White blood cell (WBC) (greater than 3000/mm^3).

                    3. Platelet count greater than 90,000/mm^3.

                    4. Hemoglobin greater than 8.0 g/dl.

              10. Chemistry:

                    1. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less
                       or equal to 2.5 times the upper limit of normal.

                    2. Serum creatinine less than or equal to 1.6 mg/dl.

                    3. Total bilirubin less than or equal to 1.5 mg/dl, except in patients with
                       Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

        EXCLUSION CRITERIA:

          1. Ocular or mucosal melanoma.

          2. Undergoing or have undergone in the past 3 weeks any systemic therapy except surgery
             for their cancer, and must have recovered to a grade 1 from any adverse effects of
             treatment prior to entry, other than those that do not have clinical implications,
             e.g. vitiligo, alopecia.

          3. Have autoimmune disease (such as autoimmune colitis or Crohn's disease) or any known
             immunodeficiency disease, as evidenced by abnormal white blood count (WBC) count.

          4. Concurrent systemic steroid therapy.

          5. Known systemic hypersensitivity to any of the vaccine components, including egg
             products or Neomycin.

          6. Women of child-bearing potential who are pregnant or breastfeeding because of the
             potentially dangerous effects of the treatment on the fetus or infant.

          7. Have active systemic infections including concurrent 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).

          8. Previous immunization with melanoma antigen recognized by T cells (MART-1).

          9. Known hypersensitivity to any of the agents used in this study.