Study of the Modulatory Activity of an LHRH-Agonist (Leuprolide) on Melanoma Peptide Vaccines as Adjuvant Therapy in Melanoma Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 98
- 试验地点
- 1
- 主要终点
- Number of Participants With T-cell Response to Peptide Vaccine
研究概览
简要总结
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:
- 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:
- 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.
- To assess whether there are significant differences in overall quality of life (QOL) between patients receiving Leuprolide to those not receiving leuprolide.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HLA-A *0201 positive
- •Patients >/= 18 years old with histologically documented diagnosis of stage IIb-IV melanomas and are clinically rendered free of disease after surgery
- •Uveal melanoma patients following definitive treatment of radiation therapy and/or enucleation.
- •Karnofsky Performance Scale >/= 60%.
- •White Blood Count (WBC) >/= 3000/mm^
- •Platelet count >/= 90,000mm^
- •Serum creatinine </= 2.0mg/dl.
- •Serum alanine aminotransferase (ALT) </= 3 times upper limit of normal(ULN))
- •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.
- •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.)
- •Negative pregnancy test by serum or urine b-HCG test for women who have menstruation in the past 12 months and without sterilization surgery.
- •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.
排除标准
- •Prior systemic therapy (including immunomodulate agents), radiation or surgery requiring general anesthesia for melanoma within 28 days of starting study treatment.
- •Autoimmune diseases.
- •Concurrent systemic or inhaled steroid therapy.
- •Any form of active primary or secondary immunodeficiency.
- •History of immunization with gp100 or MAGE-
- •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.
- •Received a Luteinizing hormone-releasing hormone (LHRH) agonist within the past 5 years.
- •Use of oral contraceptive, hormone replacement therapy or androgen preparations.
- •Hypersensitivity to gonadotropin-releasing hormone analogues.
- •Active systemic infections requiring intravenous antibiotics.
- •Lactating women or women planning lactation during the study.
研究组 & 干预措施
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)).
干预措施: Leuprolide (Drug)
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)).
干预措施: Leuprolide (Drug)
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)).
干预措施: MAGE-3 Peptide (Biological)
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
干预措施: MAGE-3 Peptide (Biological)
结局指标
主要结局
Number of Participants With T-cell Response to Peptide Vaccine
时间窗: 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.
次要结局
- Most Frequent and Most Serious Participant Adverse Events During Vaccine Treatment for Overall Study(Baseline up to 48 weeks during vaccine treatment)
- Number of Participants Experiencing Adverse Events by Maximum Grade Within Different Arms(Baseline up to 48 weeks during vaccine treatment)
- Summary of Adverse Events by Grade/Relationship(Baseline up to 48 weeks during vaccine treatment)