Adjuvant Therapy of Pegylated Interferon- 2b Plus Melanoma Peptide Vaccine

The goal of this clinical research study is to find the best dosing schedule of a combined treatment of PEG Intron® (pegylated Interferon-alfa 2b) plus a peptide vaccine (gp100) that may help improve immune response in patients that had Stage II or Stage III melanoma and are free of the disease. The safety and tolerability of this drug combination will also be studied.

The Study Drugs:

Pegylated Interferon alfa-2b is a protein made by the human immune system that helps to fight viral infections and regulate cell function.

Gp100 is a protein that is found on melanoma cells. In laboratory studies, the gp100 vaccine has been shown to stimulate the immune system to "recognize" and kill melanoma cells that have gp100 on their cell surfaces.

Evaluation of Immune cell response to vaccine:

Blood (about 3-1/2 tablespoons) will be drawn on Weeks 4, 7,10,13,16,19, and 22 for tests to check the response of your immune system to the vaccine, before each injection.

Parts of the Study:

There are 2 parts to this study, an Induction Phase and a Maintenance Phase. The Induction Phase treatment is the first course of treatment used to stimulate ("turn on") an immune-cell response to fight cancer and to learn the body's response to the treatment. The Maintenance Phase treatment is continued therapy and is used to maintain the immune-cell response and to help keep the disease in remission.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the roll of dice) to 1 of 3 treatment groups. You will have an equal chance of being assigned to one of each of the groups. Participants in each group will receive the same dose levels of pegylated Interferon alfa-2b and gp100. The difference between each group will be the dosing schedule of pegylated Interferon alfa-2b.

You will give yourself the pegylated Interferon alfa-2b at home, and the gp100 will be given to you by the research nurse in the clinic. You will be shown how to give yourself Pegylated Interferon alfa-2b at home.

Pegylated Interferon alfa-2b will be given immediately after the GP-100 Peptide Vaccine injection.

Participants in Group 1 will take pegylated Interferon alfa-2b at a certain dose level once a week for 4 weeks (in the Induction Phase), followed by once a week for 20 weeks in the Maintenance Phase (when the drug will be taken at a lower dose level than during Induction).

Participants in Group 2 will take pegylated Interferon alfa-2b at a certain dose level once a week for 8 weeks (in the Induction Phase), followed by once a week for 16 weeks in the Maintenance Phase (when the drug will be taken at a lower dose level than during Induction).

Participants in Group 3 will take pegylated Interferon alfa-2b at a certain dose level once a week for 12 weeks (in the Induction Phase), followed by once a week for 12 weeks in the Maintenance Phase (when the drug will be taken at a lower dose level than during Induction).

Study Treatment:

You will take pegylated Interferon alfa-2b as an injection just under your skin. You will receive gp100 as an injection just under your skin once every 3 weeks.

On Week 1, PEG-Intron will be given right after GP-100 Peptide Vaccine injection in the clinic. You will be observed for at least 30 minutes after both GP-100 Peptide Vaccine and PEG-Intron Injections.

On Weeks 4, 7, 10, 13, 16, 19, and 22 (+/- 1 day, not counting institutional holidays), GP-100 peptide will be given in the clinic. You will be observed for at least 30 minutes after GP-100 Peptide Vaccine injection. You should give the PEG-Intron to yourself on the same day of GP-100 Peptide Vaccine injection. The injection of gp100 will be given in two separate areas of your limbs, such as in an upper arm or thigh. It will be given in the same area each time.

Length of Study:

You will remain on this study for up to 25 weeks, unless the disease comes out of remission or you experience intolerable side effects.

End-of-Treatment Visit:

At the end of study treatment (approximately 3 weeks after the last injection of gp100), you will have the following tests:

• You will have a review of your general health and any medical problems you may be having.
• You will have a physical exam, including measurement of your vital signs.
• Blood (about 1 tablespoon) will be drawn for routine tests.
• You will have the leukapheresis repeated.
• You will have a CT scan of chest, stomach, and pelvis, and you will have an MRI or CT scan of the brain.

While you are on this study no steroids will be allowed while on treatment.

This is an investigational study. Pegylated Interferon alfa-2b is FDA approved and commercially available for the treatment of chronic hepatitis C. Gp100 is not FDA approved or commercially available. At this time, the combination use of pegylated Interferon alfa-2b plus gp100 is being used for research purposes only in this study.

Up to 30 patients will take part in this study. All will be enrolled at M. D. Anderson.

• Drug: Pegylated Interferon-Alfa 2b (PEG Intron)

  Group 1:

  6 mcg/kg by injection under skin once weekly for 4 weeks, followed by Maintenance Phase of 3 mcg/kg weekly for 20 weeks.

  Group 2:

  6 mcg/kg by injection under skin once weekly for 8 weeks, followed by Maintenance Phase of 3 mcg/kg weekly for 16 weeks.

  Group 3:

  6 mcg/kg by injection under skin once weekly for 12 weeks followed by Maintenance Phase of 3 mcg/kg weekly for 12 weeks.

  Other Name: Peginterferon alfa-2b
• Drug: GP-100 Peptide Vaccine
  Injection under skin once every 3 weeks (Weeks 1, 4, 7, 10, 13, 16, 19, and 22), for a total of 8 injections.
  Other Names:

  • GP-100 Peptide Vaccine
  • melanoma peptide gp100 vaccine

• Experimental: Group 1
  Pegylated Interferon alfa-2b (Once week x 4 weeks) + GP-100 Peptide
  Interventions:

  • Drug: Pegylated Interferon-Alfa 2b (PEG Intron)
  • Drug: GP-100 Peptide Vaccine
• Experimental: Group 2
  Pegylated Interferon alfa-2b (Once week x 8 weeks) + GP-100 Peptide
  Interventions:

  • Drug: Pegylated Interferon-Alfa 2b (PEG Intron)
  • Drug: GP-100 Peptide Vaccine
• Experimental: Group 3
  Pegylated Interferon alfa-2b (Once week x 12 weeks) + GP-100 Peptide
  Interventions:

  • Drug: Pegylated Interferon-Alfa 2b (PEG Intron)
  • Drug: GP-100 Peptide Vaccine

Inclusion Criteria:

1. Patients must be free of disease after surgical resection for AJCC stage II or III (N1a) melanoma (T2b, T3a, T3b, T4a, T4b and N1a or N2a). Diagnosis must be confirmed by the Pathology Department of MD Anderson Cancer Center.
2. Patients must be HLA-A0201 positive.
3. Patients must be fully recovered from surgery, for at least one month, but not more than 90 days after surgery and before study entry.
4. Patients must have no other malignancies. Patients with prior history of any in situ cancer, lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or Clark I melanoma in situ or basal or squamous skin cancer are eligible. Patients with other malignancies are eligible, if they have been continuously disease-free for 5 years prior to the time of study entry.
5. Patients must be >/= 18 years of age.
6. Patients must give signed written informed consent.
7. Women of childbearing potential (WOCBP) must not be pregnant (negative urine HCG within 2 weeks of treatment) or lactating. A WOCBP has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses at any time in the preceding 24 consecutive months).
8. Women of childbearing potential and sexually active males must be counseled to use an accepted and effective method of contraception (including abstinence) while on treatment and for a period of 3 months after completing or discontinuing treatment. Simultaneous use of two contraceptive methods such as, IUD or condom and contraceptive jelly is considered the accepted method of contraception.
9. Patients must have ECOG performance status 0 or 1.
10. Patients must have WBC >/= 3,000/mm3, platelet count >/= 100,000/mm3, and hemoglobin >/= 9 g/dL or 5.6 mmole/L obtained within 2 weeks of study entry.
11. Patients must have AST, ALT, LDH, alkaline phosphatase, and bilirubin within institutional upper limit (IUL) of normal and serum creatinine < 2.0 mg/dl or < 140 micromol/L all obtained within 2 weeks of study entry. Patients with Gilbert's Disease may have bilirubin </= to 2 x (ULN).
12. Patients must have a CT of chest, abdomen, pelvis, and a MRI or CT scan of the brain performed within 4 weeks of study entry.

Exclusion Criteria:

1. Patients with clinical, radiological/laboratory or pathological evidence of incompletely resected melanoma or any distant metastatic disease.
2. Patients with autoimmune disorders or receiving immunosuppressive therapy including chemotherapy, steroids or methotrexate.
3. Patients requiring consistent use of antihistamines or non-steroidal anti-inflammatory drugs.
4. Patients with a history of active ischemic heart disease or cerebro-vascular disease, congestive heart failure (NYHA class >2) or anginal syndrome requiring ongoing medical treatment.
5. Patients have a diagnosis or evidence of organic brain syndrome or significant impairment of basal cognitive function or any psychiatric disorder that might preclude participation in the protocol.
6. Patients having prior radiotherapy, chemotherapy or any immunotherapy including, tumor vaccines, interferon, interleukins, levamisole or other biologic response modifiers for any type of cancer.
7. Patients with a history of CNS demyelinating, inflammatory disease or hereditary or acquired grade 2 or higher peripheral neuropathy.
8. Patients with any other significant medical or surgical condition or psychiatric disorder, with known history of HIV or hepatitis infection may interfere with the completion of this trial or with the evaluation of safety and efficacy of the study compound.
9. Patients with thyroid dysfunction not responsive to therapy.
10. Patients with pre-existing psychiatric condition, including but not limited to: a. History of severe depression including the following 1) Hospitalization for depression 2) Electroconvulsive therapy for depression 3) Depression that resulted in a prolonged absence from work and/or significant disruption of daily functions. b. Suicidal or homicidal ideation and/or suicidal or homicidal attempt. c. History of severe psychiatric disorders (eg. psychosis, post-traumatic stress disorder or mania). d. Past history or current use of lithium and/or antipsychotic drugs.