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Melanoma Vaccine With Peptides and Leuprolide

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00254397
Recruitment Status : Completed
First Posted : November 16, 2005
Results First Posted : October 16, 2019
Last Update Posted : October 16, 2019
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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

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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.


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Study Type : Interventional  (Clinical Trial)
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 : November 2005
Actual Primary Completion Date : October 2012
Actual Study Completion Date : October 2012


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 Name: 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 Name: MAGE-3




Primary Outcome Measures :
  1. Number of Participants With T-cell Response to Peptide Vaccine [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00254397


Locations
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United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
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Principal Investigator: Patrick Hwu, MD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00254397     History of Changes
Other Study ID Numbers: 2004-0502
First Posted: November 16, 2005    Key Record Dates
Results First Posted: October 16, 2019
Last Update Posted: October 16, 2019
Last Verified: September 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:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Leuprolide
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents