Melanoma Vaccine With Peptides and Leuprolide

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00254397
• Collaborator: (none)
• Enrollment: 98
• Location: 1
• Arms: 4
• Duration (Months): 83
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Drug: Leuprolide; Biological: GP100: 209-217(210M) Peptide; Biological: MAGE-3 Peptide	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 98 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Study of the Modulatory Activity of an LHRH-Agonist (Leuprolide) on Melanoma Peptide Vaccines as Adjuvant Therapy in Melanoma Patients
• Study Start Date: Nov 1, 2005
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: gp100 + Leuprolide 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)).	Drug: Leuprolide; A 3-month 11.25 mg sustained-release formulation will be administrated intramuscularly at time 0, and approximately 12 weeks (2 injections).; Other Names: Lupron Depot Lupron ; Biological: GP100: 209-217(210M) Peptide; 1.0 ml subcutaneous injection in extremities.
Experimental: gp100 - No Leuprolide Group IB: HLA-A*0201 positive/HLA-DP4 negative treated with gp100 (1.0 ml subcutaneous injection in extremities) - No Leuprolide	Biological: GP100: 209-217(210M) Peptide; 1.0 ml subcutaneous injection in extremities.
Experimental: gp100 + MAGE-3 + 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)).	Drug: Leuprolide; A 3-month 11.25 mg sustained-release formulation will be administrated intramuscularly at time 0, and approximately 12 weeks (2 injections).; Other Names: Lupron Depot Lupron ; Biological: GP100: 209-217(210M) Peptide; 1.0 ml subcutaneous injection in extremities.; Biological: MAGE-3 Peptide; 1.0 ml subcutaneous injection in extremities.; Other Names: MAGE-3
Experimental: gp100 + MAGE-3 - No Leuprolide 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	Biological: GP100: 209-217(210M) Peptide; 1.0 ml subcutaneous injection in extremities.; Biological: MAGE-3 Peptide; 1.0 ml subcutaneous injection in extremities.; Other Names: MAGE-3

Outcome Measures

Primary Outcome Measures

1. Number of Participants With T-cell Response to Peptide Vaccine [At 3 months following initial vaccine.]

   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.

Secondary Outcome Measures

1. Most Frequent and Most Serious Participant Adverse Events During Vaccine Treatment for Overall Study [Baseline up to 48 weeks during vaccine treatment]

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

2. Number of Participants Experiencing Adverse Events by Maximum Grade Within Different Arms [Baseline up to 48 weeks during vaccine treatment]

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

3. Summary of Adverse Events by Grade/Relationship [Baseline up to 48 weeks during vaccine treatment]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. HLA-A *0201 positive

2. Patients >/= 18 years old with histologically documented diagnosis of stage IIb-IV melanomas and are clinically rendered free of disease after surgery

3. Uveal melanoma patients following definitive treatment of radiation therapy and/or enucleation.

4. Karnofsky Performance Scale >/= 60%.

5. White Blood Count (WBC) >/= 3000/mm^3.

6. Platelet count >/= 90,000mm^3.

7. Serum creatinine </= 2.0mg/dl.

8. Serum alanine aminotransferase (ALT) </= 3 times upper limit of normal(ULN))

9. Total bilirubin equal or less than 2 times upper limit of normal (ULN)), except for patient with Gilbert's syndrome who must have a total bilirubin less than 3.0mg/dl.

10. Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)

11. Negative pregnancy test by serum or urine b-HCG test for women who have menstruation in the past 12 months and without sterilization surgery.

12. Unless surgically sterile by bilateral tubal-ligation or vasectomy of partner(s), the subject agrees to continue to use a barrier method of contraception throughout the study such as: condom, or diaphragm, or sponge plus spermicide. Abstinence is an acceptable form of birth control.

Exclusion Criteria:

1. Prior systemic therapy (including immunomodulate agents), radiation or surgery requiring general anesthesia for melanoma within 28 days of starting study treatment.

2. Autoimmune diseases.

3. Concurrent systemic or inhaled steroid therapy.

4. Any form of active primary or secondary immunodeficiency.

5. History of immunization with gp100 or MAGE-3.

6. Prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, surgically treated Stage I or II cancer from which the patient is currently in complete remission (at least for 5 years), or any other cancer from which the patient has been disease-free for 5 years.

7. Received a Luteinizing hormone-releasing hormone (LHRH) agonist within the past 5 years.

8. Use of oral contraceptive, hormone replacement therapy or androgen preparations.

9. Hypersensitivity to gonadotropin-releasing hormone analogues.

10. Active systemic infections requiring intravenous antibiotics.

11. Lactating women or women planning lactation during the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UT MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center

Investigators

• Principal Investigator: Patrick Hwu, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• UT MD Anderson Cancer Center

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00254397
• Other Study ID Numbers: 2004-0502
• First Posted: Nov 16, 2005
• Last Update Posted: Oct 16, 2019
• Last Verified: Sep 1, 2019

• Keywords provided by M.D. Anderson Cancer Center: Melanoma; Uveal Melanoma; Peptide Vaccine; LHRH-agonist; Leuprolide; Lupron; MAGE-3 Peptide; MAGE-3; GP100 Peptide; Melanoma vaccines; Tumor fighting immune cells; T cells; Skin Cancer; Eye Cancer
• Additional relevant MeSH terms: Melanoma; Leuprolide

Study Results

Participant Flow

Recruitment Details	Dates of Recruitment Period: November 8, 2005 to August 11, 2009. All participants recruited the University of Texas (UT) MD Anderson Cancer Center.

Arm/Group Title	gp100 + Leuprolide	gp100 - No Leuprolide	gp100 + MAGE-3 + Leuprolide	gp100 + MAGE-3 - No Leuprolide
Arm/Group Description	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
Period Title: Overall Study
STARTED	10	6	37	45
COMPLETED	4	5	18	20
NOT COMPLETED	6	1	19	25

Baseline Characteristics

Arm/Group Title	gp100 + Leuprolide	gp100 - No Leuprolide	gp100 + MAGE-3 + Leuprolide	gp100 + MAGE-3 - No Leuprolide	Total
Arm/Group Description	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	Total of all reporting groups
Overall Participants	10	6	37	45	98
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	9 90%	5 83.3%	27 73%	31 68.9%	72 73.5%
>=65 years	1 10%	1 16.7%	10 27%	14 31.1%	26 26.5%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	48.5	43.5	55	54	53
Sex: Female, Male (Count of Participants)
Female	5 50%	1 16.7%	11 29.7%	18 40%	35 35.7%
Male	5 50%	5 83.3%	26 70.3%	27 60%	63 64.3%
Region of Enrollment (participants) [Number]
United States	10 100%	6 100%	37 100%	45 100%	98 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With T-cell Response to Peptide Vaccine
Description	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.
Time Frame	At 3 months following initial vaccine.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gp100 + Leuprolide	gp100 - No Leuprolide	gp100 + MAGE-3 + Leuprolide	gp100 + MAGE-3 - No Leuprolide
Arm/Group Description	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.
Measure Participants	7	4	26	33
Count of Participants [Participants]	6 60%	1 16.7%	12 32.4%	19 42.2%

2. Secondary Outcome

Title	Most Frequent and Most Serious Participant Adverse Events During Vaccine Treatment for Overall Study
Description	Summary of most frequent adverse events collected study wide during vaccine treatment period using Common Terminology Criteria for Adverse Events v3.0 (CTCAE).
Time Frame	Baseline up to 48 weeks during vaccine treatment

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gp100 + Leuprolide	gp100 + No Leuprolide
Arm/Group Description	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.	HLA-A*0201 positive/HLA-DP4 negative treated with gp100 (1.0 ml subcutaneous injection in extremities)
Measure Participants	47	51
Elevated Creatinine	1	0
Hyperglycemia	1	0
Cardiac troponin T	1	0
Cardiac Ischema	1	0
Fatigue	15	7
Hypotension	1	0
Ruptured lumbar disc	1	0
Possible Metastatic Lung Nodule	1	0
Cellulitis	1	0
Cerebral Ischemia	1	0
Cardiac Ischemia/stent	1	0
Atrial fibrillation	2	0
Multiple Allergic Reactions	1	0

3. Secondary Outcome

Title	Number of Participants Experiencing Adverse Events by Maximum Grade Within Different Arms
Description	Maximum Grade reported for participant adverse events. collected study wide during vaccine treatment period using Common Terminology Criteria for Adverse Events v3.0 (CTCAE).
Time Frame	Baseline up to 48 weeks during vaccine treatment

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	gp100 + Leuprolide	gp100 - No Leuprolide	gp100 + MAGE-3 + Leuprolide	gp100 + MAGE-3 - No Leuprolide
Arm/Group Description	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.
Measure Participants	10	4	36	41
Grade 4-Life threatening or disabling	0 0%	0 0%	1 2.7%	0 0%
Grade 3-Severe	2 20%	0 0%	0 0%	3 6.7%
Grade 2-Moderate	5 50%	2 33.3%	21 56.8%	10 22.2%
Grade 1-Mild	2 20%	2 33.3%	7 18.9%	24 53.3%

4. Secondary Outcome

Title	Summary of Adverse Events by Grade/Relationship
Description	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.
Time Frame	Baseline up to 48 weeks during vaccine treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	gp100 + Leuprolide	gp100 - No Leuprolide	gp100 + MAGE-3 + Leuprolide	gp100 + MAGE-3 - No Leuprolide
Arm/Group Description	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.
Measure Participants	10	6	37	45
Grade 4, Unspecified Relationship	0	0	1	0
Grade 3, Possible	1	0	0	1
Grade 3, Probable	1	0	0	0
Grade 3, Unrelated	0	0	0	1
Grade 3, Unspecified Relationship	0	0	0	1
Grade 2, Definite	5	0	11	0
Grade 2, Possible	3	1	19	3
Grade 2, Probable	5	0	3	1
Grade 2, Unlikely	0	0	2	3
Grade 2, Unrelated	3	1	1	4
Grade 2, Unspecified Relationship	8	1	16	7
Grade 1, Definite	21	4	61	50
Grade 1, Possible	22	6	103	74
Grade 1, Probable	13	3	53	56
Grade 1, Unlikely	16	4	25	38
Grade 1, Unrelated	15	3	45	36
Grade 1, Unspecified Relationship	29	7	61	37
Grade 0, Possible	1	0	0	0
Grade 0, Probable	2	0	0	0
Grade 0, Unlikely	0	0	2	0
Grade 0, Unrelated	0	0	0	0
Grade 0, Unspecified Relationship	2	0	5	13

Adverse Events

Time Frame	Participants evaluated every 6 weeks up to 48 weeks during the vaccine treatment phase of the study. Active study participation period: November 2005 to October 2010 (last participant off study).
Adverse Event Reporting Description	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.
Arm/Group Title	gp100, Leuprolide, MAGE-3		gp100 + No Leuprolide
Arm/Group Description	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)		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)
All Cause Mortality
	gp100, Leuprolide, MAGE-3		gp100 + No Leuprolide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	gp100, Leuprolide, MAGE-3		gp100 + No Leuprolide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/47 (6.4%)		3/51 (5.9%)
Blood and lymphatic system disorders
Neutrophils Elevated	0/47 (0%)		1/51 (2%)
Cardiac disorders
Cardiac Ischemia/ Infarction	1/47 (2.1%)		0/51 (0%)
General disorders
Fatigue	1/47 (2.1%)		0/51 (0%)
Hepatobiliary disorders
Cholecystitis	0/47 (0%)		1/51 (2%)
Metabolism and nutrition disorders
Hyperglycemia	0/47 (0%)		1/51 (2%)
Nervous system disorders
Pain (Head/Headache)	1/47 (2.1%)		0/51 (0%)
Other (Not Including Serious) Adverse Events
	gp100, Leuprolide, MAGE-3		gp100 + No Leuprolide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/47 (100%)		51/51 (100%)
Endocrine disorders
Hot Flashes	31/47 (66%)		0/51 (0%)
General disorders
Fatigue	15/47 (31.9%)		7/51 (13.7%)
Insomnia	22/47 (46.8%)		2/51 (3.9%)
Myalgia	13/47 (27.7%)		7/51 (13.7%)
Immune system disorders
Allergic rhinitis	5/47 (10.6%)		0/51 (0%)
Infections and infestations
Fever of unknown origin	9/47 (19.1%)		3/51 (5.9%)
Infections	6/47 (12.8%)		0/51 (0%)
Lymphopenia	5/47 (10.6%)		0/51 (0%)
Metabolism and nutrition disorders
Hyperglycemia	7/47 (14.9%)		1/51 (2%)
Musculoskeletal and connective tissue disorders
Bone development abnormal	9/47 (19.1%)		0/51 (0%)
Muscle Weakness	9/47 (19.1%)		2/51 (3.9%)
Pain (Joint)	30/47 (63.8%)		5/51 (9.8%)
Nervous system disorders
Dizziness	19/47 (40.4%)		2/51 (3.9%)
Headache	25/47 (53.2%)		1/51 (2%)
Mood Alteration	46/47 (97.9%)		0/51 (0%)
Neuropathy:Sensory	45/47 (95.7%)		2/51 (3.9%)
Reproductive system and breast disorders
Gynecomastia	15/47 (31.9%)		0/51 (0%)
Impotence	15/47 (31.9%)		0/51 (0%)
Libido	19/47 (40.4%)		0/51 (0%)
Vaginitis	6/47 (12.8%)		0/51 (0%)
Skin and subcutaneous tissue disorders
Injection Site Reaction	16/47 (34%)		16/51 (31.4%)
Pruritis	12/47 (25.5%)		10/51 (19.6%)
Rash	26/47 (55.3%)		0/51 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.