Immunotherapy of Stage III/IV Melanoma Patients
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Melan-A ELA + Montanide; Melan-A ELA + NY-ESO-1b + MAGE-A10 + Montanide; Melan-A -ELA + NY-ESO-1b + MAGE-A10 peptide + Montanide + CpG; Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpG; Melan-A-EAA/ELA + NY-ESO-1 lp + MAGE-A10 + Montanide + CpG+ IL-2
Intervention description: A maximum of 3 vaccination cycles (cycles 1-3) has been given, each cycle consisting of 4 vaccines in 4 week intervals. The intervals between cycles were 8 weeks. After 3 cycles, patients without major tumor progression requiring other treatment who showed an immunological response received "booster vaccinations" every 3 months.; A maximum of 3 vaccination cycles (cycles 1-3) has been given, each cycle consisting of 4 vaccines in 4 week intervals. The intervals between cycles were 8 weeks. After 3 cycles, patients without major tumor progression requiring other treatment who showed an immunological response received "booster vaccinations" every 3 months.; A maximum of 3 vaccination cycles (cycles 1-3) has been given, each cycle consisting of 4 vaccines in 4 week intervals. The intervals between cycles were 8 weeks. After 3 cycles, patients without major tumor progression requiring other treatment who showed an immunological response received "booster vaccinations" every 3 months.; A maximum of 3 vaccination cycles (cycles 1-3) has been given, each cycle consisting of 4 vaccines in 4 week intervals. The intervals between cycles were 8 weeks. After 3 cycles, patients without major tumor progression requiring other treatment who showed an immunological response received "booster vaccinations" every 3 months.; A maximum of 3 vaccination cycles (cycles 1-3) has been given, each cycle consisting of 4 vaccines in 4 week intervals. The intervals between cycles were 8 weeks. After 3 cycles, patients without major tumor progression requiring other treatment who showed an immunological response received "booster vaccinations" every 3 months.
Intervention MeSH terms: Monatide (IMS 3015)
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Immunotherapy; Vaccination; Melanoma; Melan-A/Mart-1 peptide; MAGE-A10 peptide; NY-ESO-1 peptide; Montanide; CpG

Summary:

      The purpose of this study is to determine whether vaccination with melanoma antigen peptides
      [Melan-A/Mart-1 (both EAA and ELA), NY-ESO-1b analog, Long NY-ESO-1 LP and MAGE-A10] and
      Montanide, CpG adjuvants and low dose rIL-2 can induce an immune response in melanoma
      patients and to assess the safety of this vaccination.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed stage III or stage IV melanoma with at least one metastatic
             lymph node and/or at least one in-transit metastasis. According to the AJCC rules,
             this includes all patients with stage IV and stage III. Patients with or without
             measurable disease may be included.

          2. Tumor expression of Melan-A by reverse transcriptase and polymerase chain reaction
             (RT-PCR) analysis for patients of group I.

             Tumor expression of Melan-A and at least one of the tumor antigens MAGE-A10, NY-ESO-1,
             or LAGE-1 by rt-PCR analysis for patients of group II and III and for HLA-A2+ patients
             of groups IV and V. HLA-A2 negative patients of groups IV and V must only have
             NY-ESO-1 positive tumors to be eligible, while expression of Melan-A and MAGE-A10 is
             unimportant.

             If no frozen tissue is available, immunohistochemistry may be performed to detect
             tumor expression of Melan-A and NY-ESO-1.

          3. HLA-A2 positive (serological or molecular typing of Peripheral Blood Lymphocytes (PBL)
             for patients of groups 1 to 3. Patients of groups 4 and 5 may either be HLA-A2+ or
             HLA-A2-.

          4. Expected survival of at least five months.

          5. Full recovery from surgery.

          6. Karnofsky scale performance status of 70% or more.

          7. The following laboratory results:

             Neutrophil count sup or equal 2.0 x 10^9/L Lymphocyte count sup or equal 0.5 x 10^9/L
             Platelet count sup or equal 100 x 10^9/L Creatinine ≤ 2 mg/dL (180 micromol/L)
             Bilirubin ≤ 2mg/dL (34 micromol/L) Granulocyte count > 2.5x10^9/L AST < 2x upper limit
             of normal aPTT: within the normal ranges of the laboratory ± 25 %

          8. Age > 18 years.

          9. Able to give written informed consent.

        Exclusion Criteria:

          1. Clinically significant heart disease (NYHA Class III or IV).

          2. Other serious illnesses, e.g., serious infections requiring antibiotics, uncontrolled
             peptic ulcer, or central nervous system disorders with major dysfunction.

          3. History of immunodeficiency disease or autoimmune disease.

          4. Known HIV positivity.

          5. Known seropositivity for hepatitis B surface antigen.

          6. Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6
             weeks for nitrosoureas).

          7. Concomitant treatment with steroids, antihistamine drugs. Topical or inhalational
             steroids are permitted.

          8. Participation in any other clinical trial involving another investigational agent
             within 4 weeks prior to enrollment.

          9. Pregnancy or lactation.

         10. Women of childbearing potential not using a medically acceptable means of
             contraception.

         11. Psychiatric or addictive disorders that may compromise the ability to give informed
             consent.

         12. Lack of availability of the patient for immunological and clinical follow-up
             assessment.

         13. Coagulation or bleeding disorders.

         14. Metastatic disease to the central nervous system, unless treated and stable.