Study of MAGE-3/Melan-A/gp 100/NA17 and rhIL-12 With/Out Low Dose IL-2 in Metastatic Melanoma

• Status: Completed
• Trial end date: 2007-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Purpose of investigation: Primary hypotheses: Immunization of patients with 4 melanoma antigen peptides will induce augmented specific IFN-y-producing CD8+ T cells against all 4 antigens simultaneously. Immunization with 4 melanoma antigen peptides will increase the response rate from 10% to 30%. Administration of low-dose IL-2 following each vaccine will result in a greater than 3-fold increase in specific T cells compared to no IL-2.

Secondary hypotheses: Immunization will clear the blood of detectable circulating melanoma cells. Tumors that grow despite induction of melanoma antigen-specific T cells may lack expression of antigens, class I MHC, or the TAP peptide transporter, or may fail to show increased expression of mRNA for IFN-y or perforin. Tumors that resist vaccination may express a different array of genes than those that are susceptible to vaccination.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Chicago
• Treatments: Interleukin-2

Criteria

Inclusion Criteria:

• Histologically-confirmed melanoma with evidence of metastatic disease, either by radiologic or physical examination. In transit metastases are allowed. Biopsy should be performed to reconfirm the diagnosis in cases of doubt.

• Life expectancy of at least 12 weeks.

• Karnofsky performance status index >/=70.

• Written informed consent

• Adequate hematopoietic, renal, and hepatic function

• LDH <1.25 x ULN

• HLA typing: patient must express HLA-A2.

• Tumor biopsy: patient must agree to undergo biopsy of accessible tumor before and after therapy, when feasible, to study tumor cell properties and characteristics of immune cells.

Exclusion Criteria:

• Significant cardiovascular disease, or cardiac arrhythmia requiring medical intervention.

• Pregnant or nursing women.

• Biological therapy in the 4 weeks prior to the start of dosing.

• Prior therapy with a melanoma vaccine containing MAGE-3, Melan-A, gplOO, NA17 peptides.

• Patients with intrinsic immunosuppression, including seropositivity for HIV antibody. Patient should be tested if risk factors are identified.

• Serious concurrent infection, including active tuberculosis, hepatitis B, or hepatitis C.

• Concurrent systemic corticosteroids (except physiologic replacement doses) or other immunosuppressive drugs (eg. cyclosporin A).

• Psychiatric illness that may make compliance to the clinical protocol unmanageable or may compromise the ability of the patient to give informed consent.

• Active or history of autoimmune disease including but not limited to: rheumatoid arthritis (RF-positive with current or recent flare), inflammatory bowel disease, systemic lupus erythematosis (clinical evidence with ANA 1:80 or greater), ankylosing spondylitis, scleroderma, multiple sclerosis, autoimmune hemolytic anemia, and immune thrombocytopenic purpura.

• Active gastrointestinal bleeding or uncontrolled peptic ulcer disease. Presence of untreated brain metastases. All patients must undergo brain imaging as part of the pre-study evaluation. Only patients with no brain metastases, or with brain lesions successfully treated by stereotactic radiation or surgical removal without recurrence at 28 day follow-up, will be eligible.