Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Eye Diseases

Rare Diseases

Melanoma

Skin Neoplasms

Eye Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Reproductive Control Agents

Vaccines

Leuprolide

Antineoplastic Agents, Hormonal

Group IA: HLA-A\*0201 positive/HLA-DP4 negative treated with gp100 (1.0 ml subcutaneous injection in extremities) + Leuprolide (3-month 11.25 mg sustained-release formulation administrated intramuscularly then again 12 weeks later (2 injections)).

Group IB: HLA-A\*0201 positive/HLA-DP4 negative treated with gp100 (1.0 ml subcutaneous injection in extremities) - No Leuprolide

Group IIA: HLA-A\*0201positive/HLA-DP4 positive treated with gp100 (1.0 ml subcutaneous injection in extremities) + MAGE-3 (1.0 ml subcutaneous injection in extremities) + Leuprolide (3-month 11.25 mg sustained-release formulation administrated intramuscularly then again 12 weeks later (2 injections)).

Group IIB: HLA-A\*0201positive/HLA-DP4 positive treated with gp100 (1.0 ml subcutaneous injection in extremities) + MAGE-3 (1.0 ml subcutaneous injection in extremities) - No Leuprolide

A 3-month 11.25 mg sustained-release formulation will be administrated intramuscularly at time 0, and approximately 12 weeks (2 injections).

1.0 ml subcutaneous injection in extremities.

GP100: 209-217(210M) Peptide

MAGE-3 Peptide

Patrick Hwu, MD

The goal of this clinical research study is to learn if the drug leuprolide will increase the level of immune cells in your body. Researchers will also want to know if this drug given together with melanoma vaccines (gp100 and MAGE-3) can improve the ability of tumor fighting immune cells (T cells) to fight melanoma cells.

Primary Objective:

1. To compare the tumor-specific immune responses to melanoma-specific peptide vaccines, gp100 and MAGE-3 in the presence or absence of a luteinizing hormone-releasing hormone (LHRH) agonist-Leuprolide, in patients with stage IIb and III melanoma, uveal melanoma or stage IV melanoma that the metastatic lesion(s) has been surgically removed.

Secondary Objectives:

1. To evaluate the kinetics of enhanced thymic activity measured by TREC analysis and flow cytometric analysis following sex hormone ablation by Leuprolide in melanoma patients.
2. To assess whether there are significant differences in overall quality of life (QOL) between patients receiving Leuprolide to those not receiving leuprolide.

This study uses vaccines named gp100 or MAGE-3 to immunize patients with melanoma. The type of melanoma they will be used for contains a protein that is also found in the vaccines. These vaccines are designed to stimulate immune cells, also called T cells, to recognize and kill melanoma cells. Leuprolide will be studied to determine whether it will (is designed to) improve your response to the vaccine.

If you are eligible for this treatment, you will be assigned to one of the two groups that either receive one vaccine or two different vaccines, depending on your tissue type (either gp100 vaccine alone or gp100 and MAGE-3 vaccines). A small amount of the vaccine(s) will be injected under your skin to test your body's immune response to the vaccines. The size of the skin reaction will be measured at 48-72 hours. This skin test will be done before you receive any vaccine, at 6 months, and at 12 months, if possible.The participant and/or participant's family will be given detailed verbal and written instructions on how to measure any reaction to the skin tests. A data sheet and ruler (cm/mm) will be given to the participant.

You will then be randomly assigned (as in the toss of a coin) to one of 2 treatment groups. Participants in one group will receive leuprolide with the vaccine(s). Participants in the other group will not receive leuprolide. Which group you are assigned to will depend partially on your age.

If you are assigned to receive leuprolide injection, you will also have a bone mineral density test to check on the strength of your bones.

Before the treatment starts, you will be asked to answer a questionnaire about your quality of life and sexual functioning. Then at 3 months and 12 months of treatment, you will be asked again to answer the same questionnaire. It should take about 20 minutes each time to finish the questionnaire.

The vaccines will be injected in the skin every 3 weeks for a total of 48 weeks. Those patients in Group I will receive 32 injections of peptide, whereas those patients in Group II will receive 64 injections of peptide over a 48 week period. If you are assigned to receive leuprolide, then leuprolide will be injected in the muscle at the beginning of the study and at 12 weeks, for a total of 2 additional injections. Both the vaccine and leuprolide injections will be given each time at the melanoma outpatient clinic at M. D. Anderson.

Blood (about 4 teaspoons) will be taken at 6 weeks, 12 weeks, then every 12 weeks up to 48 weeks, or at any time if your tumor starts to grow back. Researchers will use this blood to find out how well your immune cells are working to fight your tumor cells.

At around 24 weeks and 48 weeks into treatment, your will have CT scans of the chest, abdomen and pelvis to check on the status of your disease. At around 24 weeks, if you are receiving leuprolide and had an abnormal bone mineral density test before the treatment, you will also have the second bone mineral density test to check on the strength of your bones.

You may be taken off study if your disease gets worse or intolerable side effects occur. If you are taken off study, you will be asked to have repeat scans and a physical exam, including blood (about 4 tablespoons) for routine tests.

Following the first 48 week treatment period, you will be evaluated every 3 months for one year, every 4 months for one year, every 6 months for one year, and then once a year from then on if clinically feasible.

You will have an MRI/CT of the brain, chest, abdomen and pelvis to check on the status of your disease. If your disease gets worse or intolerable side effects occur, you will be taken off study.

Blood (about 4 tablespoons) will be drawn for routine lab tests. An additional 4 tablespoons of blood will be drawn at each follow-up visit to determine how long the t-cell counts remain high.

This is an investigational study. Gp100 and MAGE-3 vaccines are experimental and authorized for research use only. Leuprolide is approved in treating prostate cancer patients and other gynecological diseases, but is not approved for treatment of melanoma. Up to 100 patients will take part in this study. All will be enrolled at M. D. Anderson.

Melanoma Vaccine With Peptides and Leuprolide

Study of the Modulatory Activity of an LHRH-Agonist (Leuprolide) on Melanoma Peptide Vaccines as Adjuvant Therapy in Melanoma Patients

Reactivity to the gp100 peptide in each participant defined as \>10 tetramer positive cells per 10\^4 CD8+ T-cells as determined by the tetramer analysis at 3 months following initial vaccine. Number of participants with response as defined reported.

The primary end point of this clinical study was the comparison of tumor-specific immune responses to melanoma-specific peptide vaccines, gp100 and MAGE-3 in the presence or absence of Leuprolide.

Gp209-2M/HLA-A\*0201 tetramers that are commercially available employed to analyze levels of gp209-2M specific CD8+ cytolytic T cells. The levels of peptide/ HLA-A\*0201 tetramer between participants' peripheral blood mononuclear cells (PBMCs) with Leuprolide injection and without Leuprolide injection compared.

Summary of most frequent adverse events collected study wide during vaccine treatment period using Common Terminology Criteria for Adverse Events v3.0 (CTCAE).

Maximum Grade reported for participant adverse events. collected study wide during vaccine treatment period using Common Terminology Criteria for Adverse Events v3.0 (CTCAE).

Summary of adverse events( AE) collected during vaccine treatment period using Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Grade 0-Sign/symptom within normal limits, Grade 1-Mild AE, Grade 2-Moderate AE, Grade 3-Severe AE, Grade 4- Life threatening or disabling AE.

M.D. Anderson Cancer Center

Although our immunologic analysis was based on patient HLA type in order to determine reactivity against particular peptides, all patients received vaccines with or without leuprolide. Therefore, in assessing toxicity we analyzed patients within these two groups.

HLA-A\*0201 positive/HLA-DP4 negative treated with gp100 (1.0 ml subcutaneous injection in extremities) with/without Leuprolide (3-month 11.25 mg sustained-release formulation administrated intramuscularly then again 12 weeks later (2 injections)); with/without MAGE-3 (1.0 ml subcutaneous injection in extremities)

gp100, Leuprolide, MAGE-3

HLA-A\*0201 positive/HLA-DP4 negative treated with gp100 (1.0 ml subcutaneous injection in extremities) without Leuprolide; with/without MAGE-3 (1.0 ml subcutaneous injection in extremities)

gp100 + No Leuprolide

gp100 + Leuprolide

gp100 - No Leuprolide

gp100 + MAGE-3 + Leuprolide

gp100 + MAGE-3 - No Leuprolide

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Patrick Hwu, MD / Professor, Melanoma Medical Oncology

Group IA: HLA-A\*0201 positive/HLA-DP4 negative treated with gp100 (1.0 ml subcutaneous injection in extremities) + Leuprolide (3-month 11.25 mg sustained-release formulation administrated intramuscularly then again 12 weeks later (2 injections)).

Leuprolide: A 3-month 11.25 mg sustained-release formulation will be administrated intramuscularly at time 0, and approximately 12 weeks (2 injections).

GP100: 209-217(210M) Peptide: 1.0 ml subcutaneous injection in extremities.

Group IB: HLA-A\*0201 positive/HLA-DP4 negative treated with gp100 (1.0 ml subcutaneous injection in extremities) - No Leuprolide

GP100: 209-217(210M) Peptide: 1.0 ml subcutaneous injection in extremities.

Group IIA: HLA-A\*0201positive/HLA-DP4 positive treated with gp100 (1.0 ml subcutaneous injection in extremities) + MAGE-3 (1.0 ml subcutaneous injection in extremities) + Leuprolide (3-month 11.25 mg sustained-release formulation administrated intramuscularly then again 12 weeks later (2 injections)).

Leuprolide: A 3-month 11.25 mg sustained-release formulation will be administrated intramuscularly at time 0, and approximately 12 weeks (2 injections).

GP100: 209-217(210M) Peptide: 1.0 ml subcutaneous injection in extremities.

MAGE-3 Peptide: 1.0 ml subcutaneous injection in extremities.

Group IIB: HLA-A\*0201positive/HLA-DP4 positive treated with gp100 (1.0 ml subcutaneous injection in extremities) + MAGE-3 (1.0 ml subcutaneous injection in extremities) - No Leuprolide

GP100: 209-217(210M) Peptide: 1.0 ml subcutaneous injection in extremities.

MAGE-3 Peptide: 1.0 ml subcutaneous injection in extremities.

Although all participants did not receive all doses of the vaccine due to tumor progression and other reasons, if samples were available after two or more vaccinations, analyses were performed.

Number of Participants With T-cell Response to Peptide Vaccine

Elevated Creatinine

Hyperglycemia

Cardiac troponin T

Cardiac Ischema

Fatigue

Hypotension

Ruptured lumbar disc

Possible Metastatic Lung Nodule

Cellulitis

Cerebral Ischemia

Cardiac Ischemia/stent

Atrial fibrillation

Multiple Allergic Reactions

HLA-A\*0201 positive/HLA-DP4 negative treated with gp100 (1.0 ml subcutaneous injection in extremities)

Although our immunologic analysis was based on participants HLA type in order to determine reactivity against particular peptides, all participants received vaccines with or without leuprolide. Therefore, in assessing toxicity we analyzed participants within these two groups.

Most Frequent and Most Serious Participant Adverse Events During Vaccine Treatment for Overall Study

Grade 4-Life threatening or disabling

Grade 3-Severe

Grade 2-Moderate

Grade 1-Mild

Only 91 participants' data was available for classification in analysis.

Number of Participants Experiencing Adverse Events by Maximum Grade Within Different Arms

Grade 4, Unspecified Relationship

Grade 3, Possible

Grade 3, Probable

Grade 3, Unrelated

Grade 3, Unspecified Relationship

Grade 2, Definite

Grade 2, Possible

Grade 2, Probable

Grade 2, Unlikely

Grade 2, Unrelated

Grade 2, Unspecified Relationship

Grade 1, Definite

Grade 1, Possible

Grade 1, Probable

Grade 1, Unlikely

Grade 1, Unrelated

Grade 1, Unspecified Relationship

Grade 0, Possible

Grade 0, Probable

Grade 0, Unlikely

Grade 0, Unrelated

Grade 0, Unspecified Relationship

Summary of Adverse Events by Grade/Relationship

Overall Study

Symptoms and General Pathology

Neoplasm Metastasis

Neoplastic Processes

Immunomodulating Agents

GP100 peptide

IL-2

Patients with metastatic melanoma who are HLA-A201+ will be immunized with a modified peptide from the gp100 molecule that contains a signal sequence designed to improve peptide presentation by antigen presenting cells. This peptide called gp100:ES209-217 (210M) will be administered either alone or in combination with high or low dose IL-2. Patients will be evaluated for clinical response, as well as undergo studies of the immunologic response to the peptide immunization.

Immunization of Patients With Metastatic Melanoma Using the GP100 Peptide Preceded by an Endoplasmic Reticulum Insertion Signal Sequence

National Cancer Institute (NCI)

Resiquimod

Immunologic Factors

1 ml of gp100 peptide vaccine and 1 ml of MAGE-3 peptide vaccine daily for 8 weeks with R848 Gel applied to gp100 injection site immediately. Injections given intradermally and subcutaneously at 2 separate sites in separate extremities. Half of each dose given one way, and half given the other way. Vaccines given on the same day. Participant receives a total of 4 injections each week.

After 8 weeks, if participant has melanoma lesions, R848 applied to half of the lesions on body for 16 weeks.

1 ml of gp100 peptide vaccine and 1 ml of MAGE-3 peptide vaccine daily for 8 weeks. Injections given intradermally and subcutaneously at 2 separate sites in separate extremities. Half of each dose given one way, and half given the other way. Vaccines given on the same day. Participant receives a total of 4 injections each week.

After 8 weeks, if participant has melanoma lesions, R848 applied to half of the lesions on body for 16 weeks.

1 ml of gp100 peptide vaccine: 0.5 ml administered intradermally and the other 0.5 ml subcutaneously in the same extremity weekly (every 7 days +/- 2 days) for 8 weeks.

gp100

Applied to the gp100 vaccine injection site immediately following the injection, allowed to air dry for 30 minutes then covered with gauze dressing.

R848 gel

1 ml of MAGE-3 peptide vaccine: 0.5 ml administered intradermally and the other 0.5 ml subcutaneously in the same extremity weekly (every 7 days +/- 2 days) for 8 weeks.

MAGE-3

Michael A. Davies, PHD

The goal of this clinical research study is to learn if the vaccines, gp100(g209-2M), and MAGE-3, when given in combination with resiquimod (R848), can help to stimulate the immune system against melanoma.

The Study Drug/Vaccines:

Resiquimod (R848) is designed to increase the production of antigen-specific T-cells, to activate immune cells, and to increase T-cells going into the tumor, which may cause the tumor cells to die.

gp100(g209-2M) and MAGE-3 are vaccines designed to stimulate immune cells, also called T-cells, which may help the immune system to recognize and kill melanoma cells.

Study Groups:

If you are found to be eligible to take part in this study, and you have metastatic melanoma, you will be assigned to Group 3. If you have had the melanoma removed and want to be treated to try to keep it from coming back, you will be randomly assigned (as in the flip of a coin) to Group 1 or 2.

* If you are in Group 1, you will receive the vaccines gp100(g209-2M) and MAGE-3 and R848 for 8 weeks. After 8 weeks, if you have melanoma lesions, you will apply R848 to half of the lesions on your body for 16 weeks.
* If you are in Group 2, you will receive only the vaccines (gp100(g209-2M) and MAGE-3) only for 8 weeks. After 8 weeks, if you have melanoma lesions, you will apply R848 to half of the lesions on your body for 16 weeks.
* If you are in Group 3, you will receive the vaccines gp100(g209-2M) and MAGE-3 and R848 for 8 weeks. After 8 weeks, if you have melanoma lesions, you will apply R848 to half of the lesions on your body for 16 weeks.

After 8 weeks, if you no longer have melanoma lesions, you will have completed the study treatment.

Study Drug/Vaccine Administration:

Once a week for 8 weeks, you will receive the vaccines, gp100(g209-2M) and MAGE-3, intradermally (through a needle into your skin) and subcutaneously (through a needle under your skin) at 2 separate sites in separate extremities. Half of each dose will be given one way, and half given the other way. These vaccines will also be given on the same day. You will receive a total of 4 injections each week.

If you are in Group 1, every time you have the vaccine injection, R848 will be applied as a gel over the gp100(g209-2M) injection site. The R848 gel will be allowed to air dry for 30 minutes and then covered with a gauze dressing which remain on overnight.

After 8 weeks, for participants with melanoma lesions, 2 times a week for 16 weeks, you will apply the R848 gel to half of the lesions on your body. You will be given written instructions and a "hands-on" demonstration on how to apply the gel. You will also be given a worksheet to help you with applying the gel.

Study Visits:

One day after your first dose of vaccine (Day 2), you will have a punch biopsy of the vaccine injection site to check your immune system. A punch biopsy is when a hollow instrument that is used to remove a small coin-shaped sample of tissue.

At Week 2, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs and weight.
* Your performance status will be recorded.
* Blood (about 1 teaspoon) will be drawn for routine tests.
* Blood (about 4 tablespoons) will be drawn to study your immune response to the vaccine combinations.
* You will have a punch biopsy of the injection site to check your immune system the day after the vaccine is given.

Every 4 weeks, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs and weight.
* Your performance status will be recorded.
* Blood (about 1 teaspoon) will be drawn for routine tests.
* Blood (about 4 tablespoons) will be drawn to study your immune response to the vaccine combinations.

Every 8 weeks, for participants with metastatic disease, the following tests and procedures will be performed:

* You will have CT or PET/CT scans of the chest, abdomen, and pelvis to check the status of the disease.
* The tumors will be measured and photographed. Your private areas will be covered (as much as possible), and a picture of your face will not be taken unless there are tumors on your face.
* If the doctor thinks it is necessary, the tumors will be measured by CT scan.
* If the doctor thinks it is needed, you will have an MRI/CT of the brain to check the status of the disease.

The day after you first start the gel (Week 8), you will have 2 punch tumor biopsies to check your immune system. One biopsy will be of a lesion with the R848 and one without, if it is available. For participants without disease, the study will be completed and your follow-up will be decided by your doctor.

At Week 0 (before vaccine is started), after treatment at Week 8 (+/- 1 week)., and Week 16 (+/- 1 week), white blood cells will be collected by leukapheresis to test for antibodies. If you have the leukapheresis, blood (about 2 teaspoons) will be drawn as well. If you do not have leukapheresis, blood (about 4 tablespoons) will be drawn instead.

The leukapheresis procedure is research-related and would not be performed as standard of care if you were not on study. Blood for the leukapheresis will be taken through a needle in a vein in one of your arms. A solution will be added to keep your blood from clotting while it goes through the machine that collects and removes white blood cells from your blood. The remaining blood is returned to you through a needle in a vein of your other arm. This is may take up to 3-4 hours. Although several pints of blood will go through the machine, only about 1/2 a pint (1 cup) will be in the machine at any time. If you cannot have a needle in your vein, this blood will be removed thorough a central venous catheter (CVC). A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. You will be given another informed consent document to sign, which describes the risks of the CVC and the care involved.

Length of Study:

You will continue to receive treatment for up to 4 6 months, as long as you may benefit from the study and are responding to the gel. You will be taken off study if the disease gets worse or you experience any intolerable side effects. If you are in the group without disease, you will not receive the study treatment.

Follow-Up:

All three groups will be called 1 time a month for 12 months after coming off the study drugs to check on the status of the disease.

This is an investigational study. The study drugs/vaccines gp100(g209-2M), MAGE-3, and R848 are not FDA approved or commercially available. At this time, they are only being used in research.

Up to 71 participants will take part in this study. All will be enrolled at MD Anderson.

Tumor and Vaccine Site With a Toll Like Receptor (TLR) Agonist

Activation of pDCs at the Tumor and Vaccine Site With a Toll Like Receptor (TLR) Agonist

T-cell response to gp100(g209-2M) +/- MAGE3 measured at 8 weeks using a tetramer/multimer assay measured by flow cytometry. Based on the number of gp100(g209-2M) +/- MAGE3 T-cells measured, categorized as either immune responders or immune non-responders. T-cell response to the gp100(g209-2M) + /- MAGE3 peptide in each participant defined as ≥0.1% gp100(g209-2M) tetramer+ cells in the CD8+ T-cell population or ≥0.1% MAGE3 multimer cells in the CD4+ T-cell population.

Differences determined in each of these parameters between the pretreatment and post-treatment samples for each of the biopsied lesions for each participant.

1 ml of gp100 peptide vaccine and 1 ml of MAGE-3 peptide vaccine daily for 8 weeks with R848 Gel applied to gp100 injection site immediately.

Group 1: GP100 and MAGE-3 + R848

1 ml of gp100 peptide vaccine and 1 ml of MAGE-3 peptide vaccine daily for 8 weeks.

Group 2: GP100 and MAGE-3

Group 3-Metastatic Melanoma: GP100 + MAGE-3 + R848

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Michael Davis, PHD., Chair, Melanoma Medical Oncology

The original PI is no longer in the institution. Due to the absence of the original PI is no longer in the institution and the data is unavailable. The analysis for the primary outcome measure the comparison of immune responses of vaccine+R848 to vaccine alone is not available. All efforts were made to retrieve data.

Comparison of Immune Responses of Vaccine+R848 to Vaccine Alone

The original PI is no longer in the institution. Due to the absence of the original PI is no longer in the institution and the data is not available. The analysis for the secondary outcome measure the composite of Immune Cell Infiltration for pDCs, mDCs, and NK cells in Tumor Biopsy Samples data is unavailable .All efforts were made to retrieve data.

Composite of Immune Cell Infiltration for pDCs, mDCs, and NK Cells in Tumor Biopsy Samples

Recurrence

Analgesics

Anti-Infective Agents

Interleukin-2

Monatide (IMS 3015)

polysaccharide-K

Analgesics, Non-Narcotic

Adjuvants, Immunologic

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antiviral Agents

Interferons

Protective Agents

Radiation-Protective Agents

melanoma antigen recognized by T-cells (MART)-1:27-35 peptide every three weeks for four cycles (Arm I).

High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm I (Arm IA)

27-35(27L):melanoma antigen recognized by T-cells (MART)-1 peptide every three weeks for four cycles (Arm II).

High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm II (Arm IIA)

melanoma antigen recognized by T-cells (MART)-1:26-35(27L) peptide every three weeks for four cycles (Arm III).

High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm III (Arm IIIA)

27-35(27L):melanoma antigen recognized by T-cells (MART)-1 peptide plus the gp100:209-217(210M) peptide emulsified together every three weeks for four cycles (Arm IV).

High-dose (HD) bolus interleukin-2 (IL-2) (720,000 IU/kg every 8 hours for up to 12 doses) after enrollment on Arm IV (Arm IVA)

Glycoprotein 100 (GP100): 209-217 (210M)

720,000 IU/kg as an intravenous bolus over a 15 minute period every 8 hours and continuing for up to 4 days (a maximum of 12 doses).

Interleukin-2 (IL-2)

Montanide ISA 51

Melanoma antigen recognized by T-cells (MART)-1: 27-35

27-35 (27L): melanoma antigen recognized by T-cells (MART)-1

melanoma antigen recognized by T-cells (MART)-1: 26-35(27L)

Steven A Rosenberg, M.D.

This study will examine the effectiveness and side effects of an experimental vaccine to prevent recurrence of melanoma. The likelihood of melanoma returning is higher in patients who have melanoma lesions deep in the skin, in patients who have had positive lymph nodes, and in patients who have had surgery for metastatic disease (cancer that has spread beyond the primary site). Melanoma tumors produce proteins called glycoprotein 100 (gp100) and melanoma-associated antigen recognized by T cells 1 (MART-1). Vaccination with specific pieces of these proteins (peptides) may boost the immune system's fight against the cancer. The vaccine injections are mixed with an oil-based substance called Montanide ISA-51, which is intended to increase the immune response to the peptide.

Patients 16 years of age and older whose melanoma has been surgically removed and who are currently free of disease may be eligible for this study. Candidates will be screened with a physical examination and blood and urine tests. An electrocardiogram (EKG), x-rays and other imaging studies will be done if recent results are not available. Some candidates may require heart tests, such as a cardiac stress test or echocardiogram, or lung function tests. In addition, all candidates will be tested for human leukocyte antigen (HLA) tissue type; patients must be type human leukocyte antigens (HLA-A)\*0201, the type on which this vaccine is based.

Participants will be randomly assigned to receive one of four different vaccines to determine which peptides offer the best immunity. Each treatment course consists of two injections of the vaccines every 3 weeks for four times. The injections are given under the skin of the thigh. After every other treatment course (every 6 months), patients will undergo a series of x-rays and scans to look for tumor. The immunizations may continue for up to 12 months as long as the melanoma does not return. The injections are given at the National Institutes of Health (NIH) Clinical Center. Patients are monitored for 1 hour after each injection and have blood tests and a physical examination to look for treatment side effects.

Patients will be followed with blood tests every 12 weeks to monitor body functions. They will also undergo leukapheresis-a procedure to collect white blood cells-before starting treatment and about 3 to 4 weeks after the fourth vaccine to evaluate how the vaccines affect the action of the immune system cells. For this procedure, blood is drawn through a needle in the arm, similar to donating blood. The blood goes through a machine that separates out the lymphocytes (white blood cells), and the rest of the blood is returned through a needle in the other arm. Some patients may undergo a biopsy-surgical removal of a small piece of tissue under local anesthetic-of normal skin and tumor or lymph node tissue to examine the effects of the vaccines on the tumor immune cells.

Patients whose disease returns during the first course of vaccine therapy will have surgery to remove the tumor and will continue to receive the vaccine treatment. Patients whose tumor returns after completing one course of therapy may receive a substance called interleukin-2 (IL-2), which can boost immune function against the tumor. interleukin-2 (IL-2) is given intravenously (through a small tube placed in a vein) every 8 hours for 4 days. This regimen is repeated after 10 to 14 days. Those who respond to interleukin-2 (IL-2) will have a third course of treatment after 2 months. Patients whose disease recurs after treatment will be taken off the study and will be referred back to their referring physician or to another study, if an appropriate one is available.

Human leukocyte antigens (HLA-A)\*0201 positive patients at high risk for recurrence of melanoma, or completely resected metastatic melanoma will receive immunization with peptides representing human leukocyte antigen (HLA)-restricted T cell epitopes of the melanoma antigen recognized by T-cells (MART-1) or glycoprotein 100 (gp100) melanoma antigens emulsified in Montanide ISA-51 or Montanide trademark(TM) ISA 51 vegetable grade (VG). Patients will be randomized to receive one of three different melanoma antigen recognized by T-cells (MART-1) peptides or to receive a combination of a melanoma antigen recognized by T-cells (MART-1) peptide plus a glycoprotein 100 (gp100) peptide. This study is designed to evaluate the immunologic effects of the different peptide immunizations.

Peptide Vaccination for Patients at High Risk for Recurrent Melanoma

Randomized Comparison of Peptide Immunization in Patients at High Risk for Recurrence of Melanoma

Immunologic monitoring will be conducted using in vitro sensitization assays. The immunologic response in these assays will be considered positive if at least a two-fold increase in vaccine specific interferon gamma (y-IFN) secretion is seen between post vaccination specimens compared to the pre vaccination specimens.

Response is measured from the time measurement criteria are first met for complete response (CR) or partial response (PR) (whichever is first) until the first date that recurrent disease is objectively documented. Complete response is the disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.

Here are the number of participants with adverse events. For details about the adverse events see the adverse event module.

Dr. Steven Rosenberg

Adj-2 MART-1: 27-35

Adj-2 HD IL-2 After MART-1: 27-35

Adj-2 27-35 (27L) MART-1 (Mod9mer) Peptide Q3wks x 4

Adj-2 HD IL-2 After 27-35 (27L): MART-1 (Mod9mer)

Adj-2 MART-1: 26-35 (27L) (Mod10mer) Peptide Q3wks x 4

Adj-2 HD IL-2 After MART-1: 26-35 (27L) (Mod10mer)

Adj-2 27-35 (27L): MART-1 + gp100: 209-217 (210M) Q3wks x 4

Adj-2 HD IL-2 After 27-35 (27L): MART-1 + gp209-2M

Age Continuous

Steven A. Rosenberg, M.D.

The number of participants analyzed and results are correct. We do not have the immunologic response rate data for all patients.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Melanoma Vaccine With Peptides and Leuprolide	NCT00254397	Melanoma	Leuprolide GP100: 209-217(... MAGE-3 Peptide	18 Years -	M.D. Anderson Cancer Center
Immunization of Patients With Metastatic Melanoma Using the GP100 Peptide Preceded by an Endoplasmic Reticulum Insertion Signal Sequence	NCT00001705	Melanoma Neoplasm Metast...	GP100 peptide IL-2	-	National Institutes of Health Clinical Center (CC)
Immunization of Patients With Metastatic Melanoma Using the GP100 Peptide Preceded by an Endoplasmic Reticulum Insertion Signal Sequence	NCT00001705	Melanoma Neoplasm Metast...	GP100 peptide IL-2	-	National Institutes of Health Clinical Center (CC)
Tumor and Vaccine Site With a Toll Like Receptor (TLR) Agonist	NCT00960752	Melanoma	gp100 R848 gel MAGE-3	18 Years -	M.D. Anderson Cancer Center
Peptide Vaccination for Patients at High Risk for Recurrent Melanoma	NCT00059475	Melanoma	Glycoprotein 10... Interleukin-2 (... Montanide ISA 5... Melanoma antige... 27-35 (27L): me... melanoma antige...	7 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for gp100 peptide