High-Dose Interleukin-2 (HDIL-2), Combined With recMAGE-A3 + AS15 ASCI
Condition: Melanoma
MeSH terms: Melanoma
Intervention: HDIL-2; recMAGE-A3 + AS15
Intervention description: 720,000 IU/kg by vein over an approximate 15 minute period every eight hours, for a maximum of 14 doses per cycle.; 300 μg plus 420 μg of CpG7909 (a part of the Adjuvant System AS15) by intermuscular injection within 24 hours from first dose of HDIL-2.
Intervention MeSH terms: Aldesleukin; Interleukin-2
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic Melanoma; Unresectable Melanoma; HDIL-2; Interleukin-2; IL-2; Aldesleukin; Proleukin; recMAGE-A3 + AS15; ASCI; recMAGE-A3; Recombinant MAGE-A3 protein; recMAGE-A3 + AS15 ASCI; MAGE-A3; MAGE-A3 ASCI

Summary:

      The goal of this clinical research study is to learn if high-dose interleukin-2 (HDIL-2),
      when given in combination with recMAGE-A3 + AS15 ASCI (Antigen-Specific Cancer
      Immunotherapeutic), can help to control unresectable or metastatic melanoma in patients whose
      tumor tissue has the MAGE-A3 protein. The safety of this drug combination will also be
      studied. Researchers will also use samples of the original tumor or metastatic tissue (for
      example, lymph nodes or liver or lung) that are collected during screening to study if
      response to the study drug is related to the genes in the tissue.
    

Eligibility criteria:

        Inclusion Criteria:

          1. STEP 1 Written informed consent has been obtained from the patient before the
             performance of any protocol-specific procedure.

          2. Male or female patient with histologically proven, measurable unresectable or
             metastatic cutaneous melanoma

          3. Patient is >/= 18 years of age.

          4. Formalin-fixed paraffin-embedded (FFPE) tumor tissue must be available for MAGE-A3
             expression screening test from cutaneous, subcutaneous, lymph node lesion, lung or
             liver lesion. Archival FFPE tumor tissue can be provided for the MAGE-A3 screening
             test, as long as the FFPE tumor tissue was obtained from a biopsy or resection and no
             systemic chemotherapy, immunotherapy or targeted therapy has been received by the
             patient between the tumor collection and the MAGE-A3 screening test. Fresh tumor
             tissue in RNAlater must be also available for gene signature testing. Patients must
             have at least one biopsiable cutaneous, subcutaneous, lymph node lesion, The tumor
             sample should be preferably from the same lesion as the FFPE tumor tissue. Cutaneous
             lesions must measure >/= 4mm and lymph nodes, subcutaneous, lung or liver lesions must
             measure >/= 1cm.

          5. STEP 2 ANA (antinuclear antibody) titer < 1:80

          6. STEP 2 The patient's tumor shows expression of MAGE-A3 gene.

          7. ECOG performance status of 0 or 1.

          8. WBC >/= 3000/mm^3 and Hemoglobin >/= 9 g/dl

          9. Platelet count >/= 100,000/mm^3.

         10. Normal AST and ALT except for patients with liver metastases, in which serum ALT and
             AST </= 2.5 X upper limit of normal (ULN) will be permitted.

         11. Creatinine </= 1.5 mg/dL

         12. Normal total bilirubin except for patients with liver metastases, in which total
             bilirubin </= 1.5 X ULN will be permitted (patients with Gilbert's syndrome must have
             a total bilirubin less that 3.0 mg/dL).

         13. LDH </= 2 X ULN

         14. Stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram or other
             stress test that will rule out cardiac ischemia) with estimated ejection fraction >50%
             within 6 months of signing consent form

         15. Pulmonary function tests showing FEV1 > 65% or FVC > 65% of predicted within 6 months
             of signing consent form

         16. Women of childbearing potential (WOCBP) must be using an adequate method of
             contraception prior to treatment, 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. In general, the decision for appropriate methods to prevent pregnancy
             should be determined by discussions between the investigator and the study subject.
             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 for 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.

         17. (Continued #16) 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 14 days before the start of treatment.

         18. Men must also agree to use an adequate method of contraception.

        Exclusion Criteria:

          1. The patient has at any time received systemic chemotherapy, immunotherapy or targeted
             therapy (except for isolated limb perfusion, interferon, or radiation in the adjuvant
             setting, as long as this was performed at least 4 weeks before first study treatment
             administration).

          2. Brain metastasis or history of brain metastasis.

          3. Any types of melanoma other than cutaneous, i.e. ocular or mucosal .

          4. The patient received any cancer immunotherapeutic containing a MAGE-A3 antigen.

          5. Patients with a history of second malignancies are eligible provided that they have
             been free of recurrence from secondary malignancy for at least 3 years, does not
             include squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ.

          6. The patient has a history of an autoimmune disease such as, but not limited to,
             multiple sclerosis, lupus, rheumatoid arthritis, and inflammatory bowel disease or an
             antinuclear antibody (ANA) titer > 1:80.

          7. The patient has a history of allergic disease or reactions likely to be exacerbated by
             any component of the study investigational compound.

          8. The patient has a family history of congenital or hereditary immunodeficiency.

          9. Known to be positive for viral hepatitis B or C (HBsAg or Anti HCV) or HIV (HIV
             antibodies) Patients should have a negative test within 6 months of starting
             treatment.

         10. Systemic steroid therapy, steroid-containing compounds or any other immunosuppressive
             agents or to be used for more than 7 consecutive days (at a dose of prednisone or
             equivalent of >/= 0.125 mg/kg/day).

         11. The patient has psychiatric or addictive disorders that may compromise his/her ability
             to give informed consent, or to comply with the trial procedures. Each patient will be
             evaluated by the principal investigator or his designee.

         12. The patient has concurrent severe medical problems, unrelated to the malignancy, that
             would significantly limit full compliance with the study or expose the patient to
             unacceptable risk. Each patient will be evaluated by the principal investigator or his
             designee.

         13. Initiation of another anti-cancer therapy.

         14. For female patients: the patient is pregnant or lactating.

         15. WOCBP who are unwilling or unable to use an acceptable contraceptive method to avoid
             pregnancy.